Atorvastatin Reduces the Survival of Candida albicans-Infected BALB/c Mice
Open accessAbstract
Several antimicrobial and immunosuppressive effects have been attributed to the statins class of antihyperlipidemia drugs. Several studies have also indicated clinical benefits for the use of statins during the management of infections and sepsis. To assess whether the immunosuppressive effects of statins outweigh their antimicrobial effects during a fungal infection BALB/c mice were administered Candida albicans via intraperitoneal injection. These mice received either a co-injection of atorvastatin along with the infection, were treated with one injection of atorvastatin per day for 5 days prior to infection, or were infected and then treated with one injection of atorvastatin for 5 days afterward. Groups that received C. albicans without being treated with atorvastatin were included as controls along with a group that only received phosphate-buffered saline. Mouse survival was then monitored; additionally, serum IFN-γ and IL-4 levels were determined by enzyme linked immunosorbent assay to assess pro-inflammatory and pro-humoral responses, respectively. Atorvastatin administration was capable of altering mouse survival rate with the lowest rate (11.1%) being observed in the group treated for 5 days prior to infection with atorvastatin compared to mice infected but not treated with atorvastatin (44.4%). IFN-γ and IL-4 levels were depressed in all C. albicans-infected groups treated with atorvastatin. The possibility that statin administration may suppress or modulate particular components of the immune system during an infection in man should be further explored in large randomized controlled trials.
AI snapshot
Written from the paper’s full text.
TL;DR
Atorvastatin treatment reduced survival in BALB/c mice infected intraperitoneally with Candida albicans, especially when given for 5 days before infection. The authors attribute this to atorvastatin’s immunosuppressive effects outweighing its antifungal effects, with suppressed IFN-γ and IL-4 and no notable difference in fungal burden.
Key findings
- Survival at the end of 18-day monitoring was lowest at 11.1% in mice treated with atorvastatin for 5 days pre-infection, compared with 44.4% in infected untreated mice; post-infection treatment gave 22.2%, and co-injection with infection gave 44.4%. PBS-only controls showed 100% survival.
- Atorvastatin-treated infected mice showed a 95-fold decrease in serum IFN-γ and a 2222-fold decrease in serum IL-4 on day 3 post-infection compared with infected untreated mice.
- No notable differences in fungal burden were detected between statin-treated and untreated groups after culturing liver, spleen, and heart; death was verified as due to systemic C. albicans infection.
Methods
- Five groups of 9 BALB/c mice (4–6 weeks old) were infected intraperitoneally with 10.8 × 10^7 CFUs of C. albicans ATCC 14053. Atorvastatin was given intraperitoneally at 40 mg/kg as a co-injection, for 5 days pre-infection, or for 5 days post-infection; controls received infection alone or PBS. Mice were monitored for 18 days.
- For cytokines, a separate set of mice was treated similarly; 3 mice per group were sacrificed on day 3 post-infection, sera were pooled per group, and IFN-γ and IL-4 were measured by ELISA.
- Survival was analyzed by Kaplan–Meier and log-rank (Mantel–Cox) tests; cytokine differences were assessed by two-sample t-tests, with p < 0.05 considered significant.
Limitations
- The paper states that higher atorvastatin doses might have improved tissue distribution and prevented organism proliferation, but such doses would be outside the range used for human therapy. It also notes the 40 mg/kg mouse dose is equivalent to 3.24 mg/kg in humans, about 2.5× the currently recommended daily dose for most human subjects.
- The paper states that the findings should be further explored in large randomized controlled trials, implying the mouse model cannot establish human clinical effects.
- Evident from the text: survival groups contained 9 mice each, cytokine measurements used 3 mice per group with pooled sera, and the study used a single mouse strain, a single C. albicans strain, and a single statin, limiting generalizability.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
0 of 39 cited sources checked · 0 supported · 0 flagged
- Findingown data
In C. albicans-infected BALB/c mice, atorvastatin treatment (all regimens) resulted in a 2222-fold decrease in serum IL-4 on day 3 post-infection compared to infected untreated mice.
“Mice infected with C. albicans and treated with atorvastatin displayed a 2222-fold decrease in the level of this mediator on day 3 post-infection compared to mice infected with C. albicans but not treated with atorvastatin.”
Quote in the paperNot a substantial claim - Findingown data
No notable differences in fungal burden were detected between atorvastatin-treated and untreated C. albicans-infected mice upon culturing liver, spleen, and heart.
“Mouse death due to C. albicans infection was verified via recovering the organism from mouse liver, spleen, and heart by culture; no notable differences in fungal burden were detected between the statin treated groups and the untreated group upon culturing the indicated organs.”
Quote in the paperSubstantial claim - Findingown data
In C. albicans-infected BALB/c mice, the 5-day post-infection atorvastatin regimen resulted in a survival rate of 22.2% at the end of the monitoring period.
“The survival rate at the end of the monitoring period in the group treated for 5 days post-infection with atorvatstatin was 22.2% while it was 44.4% in the group of mice that received a single dose of atorvastatin along with infection.”
Quote in the paperSubstantial claim - Findingown data
In C. albicans-infected BALB/c mice, the 5-day pre-infection atorvastatin regimen resulted in the lowest survival rate at the end of the monitoring period (11.1%) compared to infected untreated mice (44.4%).
“Atorvastatin administration was capable of altering mouse survival rate with the lowest rate (11.1%) being observed in the group treated for 5 days prior to infection with atorvastatin compared to mice infected but not treated with atorvastatin (44.4%).”
- Also stated in: § Mouse Survival · plain
“In C. albicans-infected mice, survival analysis (p < 0.05, individual treated groups compared to the infected but untreated group) revealed that the lowest survival rate at the end of the monitoring period was 11.1%, observed in the group treated for 5 days pre-infection with atorvastatin (Figure 1).”
Quote in the paperSubstantial claim - Also stated in: § Mouse Survival · plain
- Findingown data
Survival differences between C. albicans-infected BALB/c mice treated with atorvastatin and infected untreated mice were statistically significant (p < 0.05).
“In C. albicans-infected mice, survival analysis (p < 0.05, individual treated groups compared to the infected but untreated group) revealed that the lowest survival rate at the end of the monitoring period was 11.1%, observed in the group treated for 5 days pre-infection with atorvastatin (Figure 1).”
Quote in the paperSubstantial claim
- Findingown data
The survival rate of C. albicans-infected BALB/c mice not treated with atorvastatin was 44.4% at the end of the monitoring period.
“The survival rate of the group infected with C. albicans but not treated with atorvastatin was 44.4%.”
Quote in the paperSubstantial claim - Findingown data
Atorvastatin treatment decreased survival of C. albicans-infected BALB/c mice in a regimen-dependent manner.
“We observed that treatment of C. albicans-infected mice with atorvastatin was capable of decreasing survival depending on the regimen employed.”
Quote in the paperSubstantial claim - Findingreasoning
In C. albicans-infected BALB/c mice, despite decreased IFN-γ and IL-4 in the single co-injection atorvastatin group, death rates were not enhanced.
“On the other hand, despite the decrease in detection of IFN-γ and IL-4 in the group of mice receiving a single dose of atorvastatin along with infection, death rates were not enhanced in this group.”
Quote in the paperSubstantial claim - Findingown data
Mice injected solely with PBS showed a 100% survival rate.
“A mouse group injected solely with PBS, as a negative control, showed a 100% survival rate (not shown).”
Quote in the paperNot a substantial claim - Findingown data
In C. albicans-infected BALB/c mice, atorvastatin treatment (all regimens) resulted in a 95-fold decrease in serum IFN-γ on day 3 post-infection compared to infected untreated mice.
“Mouse groups infected with C. albicans and treated with atorvastatin showed a 95-fold decrease in the levels of IFN-γ on day 3 post-infection compared to the group infected but not treated with atorvastatin (Figure 2).”
Quote in the paperSubstantial claim - Findingown data
We did not see a similar effect in BALB/c mice treated with atorvastatin.
“We did not see a similar effect in BALB/c mice treated with atorvastatin.”
Quote in the paperSubstantial claim - Interpretationreasoning
Different statins may result in different outcomes in a host- and regimen-dependent manner.
“This underscores the notion that different statins may result in different outcomes potentially in a host and regimen-dependent manner.”
Quote in the paperSubstantial claim - Interpretationreasoning
The enhanced death observed in C. albicans-infected mice treated with atorvastatin for 5 days before or after infection is likely due to the immunosuppressive effects of atorvastatin overcoming its antifungal effects.
“This indicates that the enhanced death is likely due to the immunosuppressive effects of this agent overcoming its anti-fungal effects.”
Quote in the paperSubstantial claim - Premisecitation
Atorvastatin down-regulates TLR4 expression in human CD14+ monocytes.
“A similar effect was also observed in human CD14+ monocytes treated with atorvastatin, whereby TLR 4 expression was significantly down-regulated (Methe et al., 2005).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Methe et al., 2005 source
Not checked in the free run.
- Premisecitation
Multiple studies indicate that Th17 and neutrophil responses are modulated by statin treatment.
“Multiple studies indicate that these components are modulated by statin treatment.”
Quote in the paperSubstantial claim - Premisecitation
Atorvastatin at 40 mg/Kg is not lethal to mice by itself.
“Moreover, these previous studies have shown that this dose of atorvastatin is not lethal to the mice by itself.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites El-Haibi et al., 2006 source
Not checked in the free run.
- Interpretationown data
Statins are potentially deleterious to the health and survival of a subject during an infection.
“Therefore, statins are potentially deleterious to the health and survival of a subject during an infection.”
Quote in the paperSubstantial claim- Rests on an assumption: The effects of atorvastatin on C. albicans-infected BALB/c mice can be extrapolated to humans.
- Rests on an assumption: The effects of atorvastatin are representative of statins as a class.
- Premisecitation
Atorvastatin at 40 mg/Kg is the minimum effective immunomodulatory dose in BALB/c mice.
“Atorvastatin injections were also administered intraperitoneally with each injection consisting of 40 mg/Kg, the minimum effective immunomodulatory dose in BALB/c mice as reported in our previous studies (El-Haibi et al., 2006).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites El-Haibi et al., 2006 source
Not checked in the free run.
- Study design and conductown data
Death of C. albicans-infected mice was verified as due to systemic C. albicans infection by recovering the organism from liver, spleen, and heart by culture.
“Mouse death due to C. albicans infection was verified via recovering the organism from mouse liver, spleen, and heart by culture”
- Also stated in: § Mouse Treatments and Survival Monitoring · plain
“Upon mouse death, the liver, spleen and heart were collected, homogenized and cultured to verify that death was due to systemic infection with C. albicans.”
Quote in the paperSubstantial claim - Also stated in: § Mouse Treatments and Survival Monitoring · plain
- Premisecitation
Various statins have been reported to inhibit the growth of Aspergillus, Zygomycete, Cryptococcus, and Candida species including Candida albicans.
“Various statins have been reported to inhibit the growth of Aspergillus (Macreadie et al., 2006; Yasmin et al., 2012), Zygomycete (Roze and Linz, 1998), Cryptococcus (Chin et al., 1997), and Candida species including Candida albicans (Chin et al., 1997; Song et al., 2003).”
Quote in the paperSubstantial claim0 of 3 sources checked - Interpretationown data
Statin administration may suppress or modulate particular components of the immune system during an infection.
“Their administration may suppress or modulate particular components of the immune system.”
- Also stated in: § Abstract · hedged
“The possibility that statin administration may suppress or modulate particular components of the immune system during an infection in man should be further explored in large randomized controlled trials.”
Quote in the paperSubstantial claim- Rests on an assumption: The effects of atorvastatin on C. albicans-infected BALB/c mice can be extrapolated to humans.
- Rests on an assumption: Serum IFN-γ and IL-4 levels are valid indicators of pro-inflammatory and pro-humoral immune responses, respectively.
- Also stated in: § Abstract · hedged
- Premisecitation
The dose of atorvastatin 40 mg/Kg in mice is equivalent to 3.24 mg/Kg in humans based on FDA mouse-to-human dose translation guidelines.
“Worth noting is that the dose of each atorvastatin injection administered to mice in the study at hand, 40 mg/Kg, is equivalent to a dose of 3.24 mg/Kg in man based on United States Food and Drug Administration (FDA) mouse to human dose translation guidelines (Reagan-Shaw et al., 2008).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Reagan-Shaw et al., 2008 source
Not checked in the free run.
- Premisecitation
Atorvastatin decreases Th17 responses in various models and in humans.
“Atorvastatin, among other statins, was also shown to decrease Th17 responses in various models and in humans (Aktunc et al., 2011; Li et al., 2011; Jameel et al., 2013; Lappegard et al., 2013).”
Quote in the paperSubstantial claim0 of 3 sources checked - Interpretationreasoning
The 40 mg/Kg mouse dose is about 2.5 times the currently recommended per day dose for most human subjects.
“This dose is therefore about 2.5X that currently recommended per day for the treatment of most human subjects.”
Quote in the paperNot a substantial claim - Premisecitation
In murine models, statins improve animal survival rates after septic shock induced by LPS challenge, bacterial infection, or cecal ligation and puncture.
“In murine models (Merx et al., 2005; Yasuda et al., 2006; Chaudhry et al., 2008; Rosch et al., 2010; Shinozaki et al., 2010), statins appeared to improve animal survival rates after septic shock induced by LPS challenge, bacterial infection or cecal ligation and puncture”
Quote in the paperNot a substantial claim0 of 3 sources checked
- May combine two claims. 13
- Classified as probably not a substantial claim. 18
May combine two claims.
Findingown dataIn C. albicans-infected BALB/c mice, a single co-injection of atorvastatin along with infection resulted in a survival rate of 44.4% at the end of the monitoring period, the same as infected untreated mice.
“The survival rate at the end of the monitoring period in the group treated for 5 days post-infection with atorvatstatin was 22.2% while it was 44.4% in the group of mice that received a single dose of atorvastatin along with infection. The survival rate of the group infected with C. albicans but not treated with atorvastatin was 44.4%.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataIn C. albicans-infected BALB/c mice, the single co-injection atorvastatin group had a similar final survival rate to infected untreated mice, but death events occurred at a slower pace.
“Although the survival rate of the group receiving a single injection of atorvastatin along with infection was similar to the group that received the infection alone by the end of the monitoring period, the death events in the former group occurred at a slower pace.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationFluvastatin enhances the Th1 protective response to Mycobacterium tuberculosis infection in human peripheral blood mononuclear cells via increased Caspase I activity.
“in a study investigating the in vitro role of fluvastatin in Mycobacterium tuberculosis infection in human peripheral blood mononuclear cells, fluvastatin was found to enhance the Th1 protective response to the infection (Montero et al., 2000). The proposed mechanism for this effect was an increased activity of Caspase I.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Montero et al., 2000 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationStatins have pleiotropic effects including antioxidative, anti-inflammatory, and immunomodulatory capabilities.
“Statins have various pleiotropic effects that are independent of their serum cholestrol-lowering properties. Some of those reported have included antioxidative, anti-inflammatory and immunomodulatory capabilities (Athyros et al., 2009).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Athyros et al., 2009 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationMeta-analyses and systematic reviews on statins and infection have yielded inconclusive results.
“Moreover, a considerable number of meta-analyses and systematic reviews have examined the literature on statins and infection with rather inconclusive results (Falagas et al., 2008; Gao et al., 2008; Kopterides and Falagas, 2009; Tleyjeh et al., 2009, 2012; Bjorkhem-Bergman et al., 2010; Janda et al., 2010; van den Hoek et al., 2011; Ma et al., 2012; Wan et al., 2014; Wang et al., 2014).”
Quote in the paperNot a substantial claim0 of 3 sources checkedMay combine two claims.
PremisecitationIn previous studies, atorvastatin reduced IFN-γ when mice were challenged with albumin but not when they received skin allografts.
“In our previous studies on BALB/c mice atorvastatin reduced the expression of IFN-γ when mice were challenged with albumin (El-Haibi et al., 2006) but not when they received skin allografts from C57BL/6 mice (Zeidan et al., 2013).”
Quote in the paperNot a substantial claim0 of 2 sources checkedClassified as probably not a substantial claim. May combine two claims.
PremisecitationStatins have anti-inflammatory and immunomodulatory properties affecting both Th1 and Th2 immune responses.
“Multiple reports indicate that statins have anti-inflammatory and immunomodulatory properties affecting both Th1 and Th2 immune responses (Leung et al., 2003; McKay et al., 2004; Palaniswamy et al., 2010).”
Quote in the paperSubstantial claim0 of 3 sources checkedMay combine two claims.
InterpretationcitationUpon atorvastatin treatment, other aspects of the immune response downstream of IFN-γ may be impaired, resulting in an inadequate immune response.
“Hence, upon atorvastatin treatment, whether IFN-γ levels rise or are suppressed in response to a challenge, other aspects of the immune response, including those downstream to IFN-γ, may be impaired. This would result in an inadequate immune response.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationPravastatin, simvastatin, and atorvastatin reduce neutrophil transendothelial migration.
“Pravastatin, simvastatin, and atorvastatin were shown to reduce neutrophil transendothelial migration (Maher et al., 2009)”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Maher et al., 2009 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataThe C. albicans ATCC 14053 strain used was verified susceptible to atorvastatin in vitro using CLSI guidelines.
“In vitro susceptibility of this strain to atorvastatin was verified using Clinical Laboratory Standards Institute (CLSI) guidelines.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationMulti-dosing of atorvastatin has been reported to result in cumulative blood level spikes.
“and multi-dosing has been reported to result in cumulative blood level spikes (Lins et al., 2003).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Lins et al., 2003 source
Not checked in the free run.
May combine two claims.
PremisecitationStatins including atorvastatin repress the expression of MHC II molecules induced by IFN-γ, thereby impairing T-cell activation and compromising the adaptive immune response.
“It has also been shown that statins, including atorvastatin, repress the expression of MHC II molecules induced by IFN-γ, thereby impairing T-cell activation and compromising the adaptive immune response (Kwak et al., 2000).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Kwak et al., 2000 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationPravastatin enhances the survival of C. albicans-challenged mice.
“pravastatin has been shown to enhance the survival of C. albicans- challenged mice (Tashiro et al., 2012).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Tashiro et al., 2012 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Premisenone givenSome studies have indicated that statins may have beneficial effects as therapeutic agents in infection and sepsis and as prophylactic agents that reduce the risk of infection.
“A number of studies have indicated that statins may also have beneficial effects as therapeutic agents in infection and sepsis as well as prophylactic agents that reduce the risk of infection.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationSimvastatin enhances neutrophil apoptosis.
“Moreover, simvastatin was demonstrated to enhance neutrophil apoptosis (Chello et al., 2007).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Chello et al., 2007 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Premisenone givenSome studies have shown no beneficial effects or even an increased risk of an unfavorable infection outcome with statins.
“On the other hand, some studies have shown no beneficial effects or even an increased risk of an unfavorable infection outcome.”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationOur group previously reported that atorvastatin suppresses certain aspects of both humoral and cell-mediated immunity in mice challenged with egg albumin, including suppression of IFN-γ and IL-4 production.
“Our group has previously reported a suppression of certain aspects of both the humoral and the cell-mediated branches of immunity in mice challenged with egg albumin upon treatment with atorvastatin (El-Haibi et al., 2006). We detected a suppression of IFN-γ and IL-4 production.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites El-Haibi et al., 2006 source
Not checked in the free run.
May combine two claims.
InterpretationreasoningThe effects of statins may be dependent on the type of infection, the infectious agent, and the statin regimen employed.
“our findings added to the observations denoted above indicate that the effects of statins may be dependent on the type of infection and the agent administered itself in addition to the statin regimen employed.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
PremisecitationSome studies have described potential benefits for statin use during Candida infection in mice and in a clinical setting.
“Although some studies have described potential benefits for statin use during a Candida infection both in mice (Tashiro et al., 2012) and in a clinical setting (Forrest et al., 2010; Spanakis et al., 2010; Cuervo et al., 2013)”
Quote in the paperSubstantial claim0 of 3 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing), S4 (based).
Premisenone givenA decrease in sepsis-associated mortality in human subjects on statins was presumed to be due to the immunomodulatory and anti-inflammatory properties of these drugs.
“A decrease in sepsis-associated mortality rate in human subjects on statins was presumed to be an effect of the immunomodulatory and anti-inflammatory properties of these drugs.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Premisenone givenAnimals challenged with live Staphylococcus aureus or Salmonella enterica serovar Typhimurium did not display a significant decrease in TNF-α or IL-6 levels after statin treatment.
“On the other hand, animals challenged with live Staphylococcus aureus or Salmonella enterica serovar Typhimurium did not display a significant decrease in TNF-α or IL-6 levels after treatment.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationChaudhry et al. demonstrated that mice challenged with LPS have significantly lower serum TNF-α and IL-6 upon cerivastatin treatment.
“Chaudhry et al. (2008) have demonstrated that mice challenged with LPS have significantly lower serum TNF-α and IL-6, the pro-inflammatory cytokines, upon cerivastatin treatment.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Chaudhry et al., 2008 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationLovastatin affects leukocyte mobilization and results in a Th1 to Th2 shift in a heat-inactivated Candida albicans delayed type hypersensitivity mouse model.
“lovastatin was reported to affect leukocyte mobilization and result in a Th1 to Th2 shift in a heat-inactivated Candida albicans delayed type hypersensitivity mouse model (Mira et al., 2008).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Mira et al., 2008 source
Not checked in the free run.
Classified as probably not a substantial claim.
PremisecitationTh17 and neutrophil responses play major roles in combating C. albicans infections.
“Components of the immune response previously reported to play major roles in combating C. albicans infections that may have been affected by this prolonged treatment include Th17 and neutrophil responses.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationAtorvastatin has an enhanced graft longevity effect in mice and human transplant recipients, potentially due to its immunomodulatory properties.
“Members of our group have also reported an enhanced graft longevity effect for atorvastatin, one of the most commonly used statins, in mice and in human transplant recipients; this is potentially due to atorvastatin’s immunomodulatory properties (El-Haibi et al., 2006; Rahal et al., 2012a,b; Zeidan et al., 2013).”
Quote in the paperNot a substantial claim0 of 3 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationSimilar high daily doses of atorvastatin have been used in some subject groups.
“While the dose we employed is higher than the one typically employed in man, similar high daily doses have been used in some subject groups (Cilla et al., 1996)”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Cilla et al., 1996 source
Not checked in the free run.
May combine two claims.
PremisecitationTashiro et al. reported enhanced survival and decreased fungal burden in C3H/HeN mice infected with C. albicans treated with pravastatin.
“The study by Tashiro et al. (2012), indicated above, reported enhanced survival and a decreased fungal burden in C3H/HeN mice infected with C. albicans treated with pravastatin.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Tashiro et al., 2012 source
Not checked in the free run.
The paper relies on this without support.
The effects of atorvastatin on C. albicans-infected BALB/c mice can be extrapolated to humans.
“The possibility that statin administration may suppress or modulate particular components of the immune system during an infection in man should be further explored in large randomized controlled trials.”
The paper relies on this without support.
The effects of atorvastatin are representative of statins as a class.
“Therefore, statins are potentially deleterious to the health and survival of a subject during an infection.”
The paper relies on this without support.
Serum IFN-γ and IL-4 levels are valid indicators of pro-inflammatory and pro-humoral immune responses, respectively.
“serum IFN-γ and IL-4 levels were determined by enzyme linked immunosorbent assay to assess pro-inflammatory and pro-humoral responses, respectively.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Statins have demonstrated notable antifungal potential and are being repurposed for treatment of candidiasis.
“Among the pharmacological classes under investigation, statins, widely prescribed for the management of hypercholesterolemia, have demonstrated notable antifungal potential and are being repurposed for the treatment of candidiasis [17].”
From Statins as Antifungal Agents: A Review on Drug Repurposing and Nanotechnology-Driven Delivery Strategies (2025) · cites this paper as [17]
The Introduction (page unavailable) describes statins’ antifungal properties as well documented and reports inhibition of Candida growth. It does not establish that statins are being repurposed to treat candidiasis; the Discussion (page unavailable) instead reports reduced survival in atorvastatin-treated, C. albicans-infected mice. (LLM, conf=0.88)
Experimental — accuracy not yet measuredAtorvastatin had a negative effect on the survival of mice infected with C. albicans and followed up with atorvastatin (40 mg/kg), due to decreased INF-gamma and IL-4 levels.
“Interestingly, atorvastatin had a negative effect on the survival of mice infected with C. albicans and followed up with atorvastatin (40 mg kg -1 ), and this was due to decreased INF-gamma and IL-4 levels in response to C. albicans , while the LD 50 for atorvastatin is 5000 mg kg -1 in mice [39].”
From Assessment of the in vitro and in vivo activity of atorvastatin against Candida albicans. (2019) · cites this paper as [39]
Materials and Methods reports 40 mg/kg atorvastatin injections, and Results > Mouse Survival reports lower survival after five-day pre- or post-infection treatment. The Discussion reports reduced IFN-γ and IL-4, but says immunosuppression is a likely explanation rather than establishing that those two cytokines caused the deaths; a single dose lowered both cytokines without increasing deaths. Our copy does not give an atorvastatin LD50 of 5000 mg/kg in mice. (LLM, conf=0.88)
Experimental — accuracy not yet measuredOther studies mentioned that the antifungal activities of ATO and other statin drugs can be attributed to the inhibition of ergosterol and isoprenoid-biosynthesis.
“Other studies mentioned that the antifungal activates of ATO and other statin drugs can be attributed to the inhibition of ergosterol and isoprenoid-biosynthesis are thought to result in these antifungal properties (Rahal et al. 2015; Rodrigues 2018; Lima et al. 2019)”
From In vitro study on the potential fungicidal effects of atorvastatin in combination with some azole drugs against multidrug resistant Candida albicans (2021) · cites this paper as Rahal et al. 2015
The LD50 for atorvastatin is 5000 mg/kg in mice.
“Interestingly, atorvastatin had a negative effect on the survival of mice infected with C. albicans and followed up with atorvastatin (40 mg kg -1 ), and this was due to decreased INF-gamma and IL-4 levels in response to C. albicans , while the LD 50 for atorvastatin is 5000 mg kg -1 in mice [39].”
From Assessment of the in vitro and in vivo activity of atorvastatin against Candida albicans. (2019) · cites this paper as [39]
The Materials and Methods section calls the C. albicans infectious dose sub-LD50; that is not an atorvastatin LD50. The Discussion says a 40 mg/kg atorvastatin dose was not lethal to mice by itself, but gives no atorvastatin LD50. Searches for 5000 mg/kg and atorvastatin's median lethal dose found no supporting passage in our copy (page numbers unavailable). (LLM, conf=0.75)
Experimental — accuracy not yet measured
Cites
Dose translation from animal to human studies revisited.
Reagan‐Shaw, S., Nihal, M., & Ahmad, N. (2008) · The FASEB Journal · doi:10.1096/fj.07-9574lsf · Cited by 6,524 · see citing works
Statins as a newly recognized type of immunomodulator.
Kwak, B., Mulhaupt, F., Myit, S., & Mach, F. (2000) · Nature Medicine · doi:10.1038/82219 · Cited by 1,383 · see citing works
A novel anti-inflammatory role for simvastatin in inflammatory arthritis.
Leung, B. P., Sattar, N., Crilly, A., Prach, M., McCarey, D. W., Payne, H., Madhok, R., Campbell, C., Gracie, J. A., Liew, F. Y., et al. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.170.3.1524 · Cited by 434 · see citing works
Weber, C., Erl, W., Weber, K. S. C., & Weber, P. C. (1997) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(97)00324-0 · Cited by 411 · see citing works
Inhibition of proinflammatory cytokine production by pravastatin
Rosenson, R. S., Tangney, C., & Casey, L. C. (1999) · The Lancet · doi:10.1016/s0140-6736(98)05917-0 · Cited by 376 · see citing works
A novel anti-inflammatory role of simvastatin in a murine model of allergic asthma.
McKay, A., Leung, B. P., McInnes, I. B., Thomson, N. C., & Liew, F. Y. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.5.2903 · Cited by 309 · see citing works
Inhibition of Monocyte Chemotactic Protein-1 Synthesis by Statins
Romano, M., Diomede, L., Sironi, M., Massimiliano, L., Sottocorno, M., Polentarutti, N., Guglielmotti, A., Albani, D., Bruno, A., Fruscella, P., et al. (2000) · Laboratory Investigation · doi:10.1038/labinvest.3780115 · Cited by 298 · see citing works
Statin treatment after onset of sepsis in a murine model improves survival.
Merx, M. W., Liehn, E. A., Graf, J., van de Sandt, A., Schaltenbrand, M., Schrader, J., Hanrath, P., & Weber, C. (2005) · Circulation · doi:10.1161/circulationaha.104.502195 · Cited by 287 · see citing works
Statins for the Prevention and Treatment of Infections
Tleyjeh, I. M. (2009) · Archives of Internal Medicine · doi:10.1001/archinternmed.2009.286 · Cited by 236 · see citing works
Simvastatin improves sepsis-induced mortality and acute kidney injury via renal vascular effects.
Yasuda, H., Yuen, P. S. T., Hu, X., Zhou, H., & Star, R. A. (2006) · Kidney International · doi:10.1038/sj.ki.5000300 · Cited by 209 · see citing works
Cilla, D. D., Whitfield, L. R., Gibson, D. M., Sedman, A. J., & Posvar, E. L. (1996) · Clinical Pharmacology & Therapeutics · doi:10.1016/s0009-9236(96)90218-0 · Cited by 204 · see citing works
Janda, S., Young, A. V., FitzGerald, J. M., Etminan, M., & Swiston, J. R. (2010) · Journal of Critical Care · doi:10.1016/j.jcrc.2010.02.013 · Cited by 181 · see citing works
Kleemann, R., Verschuren, L., de Rooij, B. F., Lindeman, J. H. N., de Maat, M. P. M., Szalai, A. J., Princen, H. M. G., & Kooistra, T. (2004) · Blood · doi:10.1182/blood-2003-11-3791 · Cited by 180 · see citing works
Methe, H., Kim, J.-O., Kofler, S., Nabauer, M., & Weis, M. (2005) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.0000168410.44722.86 · Cited by 172 · see citing works
Statins for infection and sepsis: a systematic review of the clinical evidence.
Falagas, M. E., Makris, G. C., Matthaiou, D. K., & Rafailidis, P. I. (2008) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkn019 · Cited by 166 · see citing works
Simvastatin suppresses endotoxin-induced upregulation of toll-like receptors 4 and 2 in vivo
Niessner, A., Steiner, S., Speidl, W. S., Pleiner, J., Seidinger, D., Maurer, G., Goronzy, J. J., Weyand, C. M., Kopp, C. W., Huber, K., et al. (2006) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2005.12.022 · Cited by 154 · see citing works
Pleiotropic effects of statins–clinical evidence.
Athyros, V., Kakafika, A., Tziomalos, K., Karagiannis, A., & Mikhailidis, D. (2009) · Current Pharmaceutical Design · doi:10.2174/138161209787315729 · Cited by 154 · cited 2× · see citing works
“Some of those reported have included antioxidative, anti-inflammatory and immunomodulatory capabilities (Athyros et al., 2009).”
BackgroundInfluentialKothe, H., Dalhoff, K., Rupp, J., Müller, A., Kreuzer, J., Maass, M., & Katus, H. A. (2000) · Circulation · doi:10.1161/01.cir.101.15.1760 · Cited by 151 · see citing works
Chakrabarti, R., & Engleman, E. G. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)98884-8 · Cited by 145 · see citing works
Growth inhibition of<i>Candida</i>species and<i>Aspergillus fumigatus</i>by statins
Macreadie, I. G., Johnson, G., Schlosser, T., & Macreadie, P. I. (2006) · FEMS Microbiology Letters · doi:10.1111/j.1574-6968.2006.00370.x · Cited by 136 · see citing works
Lins, R. L., Matthys, K. E., Verpooten, G. A., Peeters, P. C., Dratwa, M., Stolear, J.-C., & Lameire, N. H. (2003) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfg048 · Cited by 128 · see citing works
Yasmin, S., Alcazar-Fuoli, L., Gründlinger, M., Puempel, T., Cairns, T., Blatzer, M., Lopez, J. F., Grimalt, J. O., Bignell, E., & Haas, H. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1106399108 · Cited by 126 · see citing works
Rosch, J. W., Boyd, A. R., Hinojosa, E., Pestina, T. I., Hu, Y., Persons, D. A., Orihuela, C. J., & TUOMANEN, E. I. (2010) · Journal of Clinical Investigation · doi:10.1172/jci39843 · Cited by 112 · see citing works
Katznelson, S., Wang, X. M., Chia, D., Ozawa, M., Zhong, H.-C., Hirata, M., Terasaki, P. I., & KOBASHIGAWA, J. A. (1998) · PubMed · Cited by 111 · see citing works
Statins for sepsis: a critical and updated review
Kopterides, P., & Falagas, M. E. (2009) · Clinical Microbiology and Infection · doi:10.1111/j.1469-0691.2009.02750.x · Cited by 106 · see citing works
Simvastatin increases neutrophil apoptosis and reduces inflammatory reaction after coronary surgery.
Chello, M., Anselmi, A., Spadaccio, C., Patti, G., Goffredo, C., Di Sciascio, G., & Covino, E. (2007) · The Annals of Thoracic Surgery · doi:10.1016/j.athoracsur.2006.10.065 · Cited by 105 · see citing works
Chin, N. X., Weitzman, I., & Della-Latta, P. (1997) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.41.4.850 · Cited by 101 · see citing works
Montero, M. T., Hernández, O., Suárez, Y., Matilla, J., Ferruelo, A. J., Martı́nez-Botas, J., Gómez-Coronado, D., & Lasunción, M. A. (2000) · Atherosclerosis · doi:10.1016/s0021-9150(00)00417-2 · Cited by 97 · see citing works
Lovastatin Triggers an Apoptosis-like Cell Death Process in the FungusMucor racemosus
Roze, L. V., & Linz, J. E. (1998) · Fungal Genetics and Biology · doi:10.1006/fgbi.1998.1093 · Cited by 96 · see citing works
Wan, Y.-D., Sun, T.-W., Kan, Q.-C., Guan, F.-X., & Zhang, S.-G. (2014) · Critical Care · doi:10.1186/cc13828 · Cited by 95 · see citing works
Maher, B. M., Dhonnchu, T. N., Burke, J. P., Soo, A., Wood, A. E., & Watson, R. W. G. (2009) · Journal of Leukocyte Biology · doi:10.1189/jlb.0608382 · Cited by 93 · see citing works
Statins induce regulatory T cell recruitment via a CCL1 dependent pathway.
Mira, E., León, B., Barber, D. F., Jiménez-Baranda, S., Goya, I., Almonacid, L., Márquez, G., Zaballos, A., Martínez-A., C., Stein, J. V., et al. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.5.3524 · Cited by 88 · see citing works
Gao, F., Linhartova, L., Johnston, A. M., & Thickett, D. R. (2008) · British Journal of Anaesthesia · doi:10.1093/bja/aem406 · Cited by 83 · see citing works
Integrin-dependent Leukocyte Adhesion Involves Geranylgeranylated Protein(s)
Liu, L., Moesner, P., Kovach, N. L., Bailey, R. D., Hamilton, A. D., Sebti, S. M., & Harlan, J. M. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.47.33334 · Cited by 78 · see citing works
van den Hoek, H. L., Bos, W. J. W., de Boer, A., & van de Garde, E. M. W. (2011) · BMJ · doi:10.1136/bmj.d7281 · Cited by 73 · see citing works
Reversal of lovastatin‐mediated inhibition of natural killer cell cytotoxicity by interleukin 2
Cutts, J., & Bankhurst, A. D. (1990) · Journal of Cellular Physiology · doi:10.1002/jcp.1041450208 · Cited by 68 · see citing works
Li, X.-L., Dou, Y., Liu, Y., Chang-wen, S., Cao, L., Zhang, X., Zhu, J., & Duan, R. (2011) · Cellular Immunology · doi:10.1016/j.cellimm.2011.08.015 · Cited by 66 · see citing works
Song, J. L., Lyons, C. N., Holleman, S., Oliver, B. G., & White, T. C. (2003) · Medical Mycology · doi:10.1080/1369378031000137233 · Cited by 62 · see citing works
Statin Treatment and Mortality in Bacterial Infections – A Systematic Review and Meta-Analysis
Björkhem‐Bergman, L., Bergman, P., Andersson, J., & Lindh, J. D. (2010) · PLoS ONE · doi:10.1371/journal.pone.0010702 · Cited by 62 · see citing works
Wang, H., Li, J., Huang, C.-X., & Jiang, H. (2004) · Clinica Chimica Acta · doi:10.1016/j.cccn.2004.10.007 · Cited by 57 · see citing works
Chaudhry, M. Z., Wang, J. H., Blankson, S., & Redmond, H. P. (2008) · Surgical Infections · doi:10.1089/sur.2006.077 · Cited by 56 · see citing works
Lappegård, K. T., Pop‐Purceleanu, M., van Heerde, W. L., Sexton, J., Tendolkar, I., & Pop, G. (2013) · Journal of Neuroinflammation · doi:10.1186/1742-2094-10-78 · Cited by 55 · see citing works
HMG-CoA Reductase Inhibitors Pravastatin and Simvastatin Inhibit Human B-Lymphocyte Activation
Rudich, S. M., Mongini, P. K. A., Perez, R. V., & Katznelson, S. (1998) · Transplantation Proceedings · doi:10.1016/s0041-1345(98)00123-7 · Cited by 54 · see citing works
Aktunc, E., Kayhan, B., Arasli, M., Gun, B. D., & Barut, F. (2011) · Immunopharmacology and Immunotoxicology · doi:10.3109/08923973.2011.559475 · Cited by 44 · see citing works
Ma, Y., Wen, X., Peng, J., Lu, Y., Guo, Z., & Lu, J. (2012) · PLoS ONE · doi:10.1371/journal.pone.0051548 · Cited by 44 · see citing works
Jameel, A., Ooi, K. G.-J., Jeffs, N. R., Galatowicz, G., Lightman, S. L., & Calder, V. L. (2013) · International Journal of Inflammation · doi:10.1155/2013/434586 · Cited by 43 · see citing works
Tashiro, M., Kimura, S., Tateda, K., Saga, T., Ohno, A., Ishii, Y., Izumikawa, K., Tashiro, T., Kohno, S., & Yamaguchi, K. (2012) · Medical Mycology · doi:10.3109/13693786.2011.610037 · Cited by 36 · see citing works
Mechanisms underlying pleiotropic effects of statins.
Palaniswamy, C., Selvaraj, D. R., Selvaraj, T., & Sukhija, R. (2010) · American Journal of Therapeutics · doi:10.1097/mjt.0b013e31819cdc86 · Cited by 35 · see citing works
Statins in candidemia: clinical outcomes from a matched cohort study.
Forrest, G. N., Kopack, A. M., & Perencevich, E. N. (2010) · BMC Infectious Diseases · doi:10.1186/1471-2334-10-152 · Cited by 33 · see citing works
Farnesyltransferase inhibitor improved survival following endotoxin challenge in mice
Shinozaki, S., Inoue, Y., Yang, W., Fukaya, M., Carter, E. A., Ming-Yu, Y., Fischman, A. J., Tompkins, R. G., & Kaneki, M. (2009) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2009.12.094 · Cited by 32 · see citing works
Spanakis, E. K., Kourkoumpetis, T. K., Livanis, G., Peleg, A. Y., & Mylonakis, E. (2010) · Mayo Clinic Proceedings · doi:10.4065/mcp.2010.0447 · Cited by 31 · see citing works
Effect of Statin Use on Outcomes of Adults with Candidemia
Cuervo, G., Garcia-Vidal, C., Nucci, M., Puchades, F., Fernández-Ruiz, M., Mykietiuk, A., Manzur, A., Gudiol, C., Pemán, J., Viasus, D., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0077317 · Cited by 20 · see citing works
Lovastatin induces differentiation of Mono Mac 6 cells
Weber, C., Erl, W., & Weber, P. C. (1995) · Cell Biochemistry and Function · doi:10.1002/cbf.290130408 · Cited by 20 · see citing works
Ozaki, H., & Shirai, K. (2001) · PubMed · Cited by 18 · see citing works
Tleyjeh, I. M., Alasmari, F. A., Abdulhak, A. A. B., Riaz, M. A., Garbati, M. A., Erwin, P. J., Kashour, T. S., Al-Mallah, M. H., & Baddour, L. M. (2012) · Infection Control and Hospital Epidemiology · doi:10.1086/668019 · Cited by 13 · see citing works
El-Haibi, C., Rahal, E., Khauli, R. B., & Abdelnoor, A. M. (2006) · Immunopharmacology and Immunotoxicology · doi:10.1080/08923970600928056 · Cited by 7 · cited 5× · see citing works
“We used this dose since it was the lowest to have an immunomodulatory effect in BALB/c mice in our previous studies (El-Haibi et al., 2006).”
BackgroundMethodInfluentialSelf-citationRahal, E. A., Chakhtoura, M., Dargham, R. A., Khauli, R. B., Medawar, W. A., & Abdelnoor, A. M. (2012) · Immunopharmacology and Immunotoxicology · doi:10.3109/08923973.2011.653648 · Cited by 6 · see citing works
Self-citationZeidan, N. (2013) · British Journal of Medicine and Medical Research · doi:10.9734/bjmmr/2013/3338 · Cited by 1 · see citing works
Self-citationRahal, E. A. (2012) · IOSR Journal of Pharmacy (IOSRPHR) · doi:10.9790/3013-25105660 · Cited by 1 · see citing works
Self-citation[Effect of statins on occurrence of infection and infection-related mortality: a meta-analysis].
Wang, G., Zhang, Y., Xie, X., Han, D. H., Wu, Y., Li, S., Li, F., & Li, M. (2014) · PubMed · Cited by 1 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Tavakkoli, A., Johnston, T. P., & Sahebkar, A. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107483 · Cited by 73 · see citing works
Nour, E. M., El-Habashy, S. E., Shehat, M. G., Essawy, M. M., El-Moslemany, R. M., & Khalafallah, N. M. (2023) · Drug Delivery and Translational Research · doi:10.1007/s13346-023-01353-4 · Cited by 41 · see citing works
Repurposing of Existing Statin Drugs for Treatment of Microbial Infections: How Much Promising?
Rana, R., Sharma, R., & Kumar, A. (2018) · Infectious Disorders - Drug Targets · doi:10.2174/1871526518666180806123230 · Cited by 36 · see citing works
Mahmoud, D. E., Faraag, A. H. I., & Abu El-Wafa, W. M. (2021) · World Journal of Microbiology and Biotechnology · doi:10.1007/s11274-021-03158-4 · Cited by 26 · see citing works
de Oliveira Neto, A. S., Souza, I. L. A., Amorim, M. E. S., de Freitas Souza, T., Rocha, V. N., do Couto, R. O., Fabri, R. L., & de Freitas Araújo, M. G. (2021) · Medical Mycology · doi:10.1093/mmy/myaa071 · Cited by 22 · see citing works
Assessment of the in vitro and in vivo activity of atorvastatin against Candida albicans.
Ajdidi, A., Sheehan, G., Abu Elteen, K., & Kavanagh, K. (2019) · Journal of medical microbiology · doi:10.1099/jmm.0.001065 · Cited by 18 · see citing works
Effect of Statins on the Risk of Poststroke Pneumonia: National Population-Based Cohort Study
Song, T., & Kim, J. (2020) · Infection and Drug Resistance · doi:10.2147/idr.s258420 · Cited by 11 · see citing works
Li, J., Guo, J., Fan, H., Yuen, M., Yuen, H., & Peng, Q. (2025) · Food & Function · doi:10.1039/d5fo02090e · Cited by 10 · see citing works
e Silva, D. M., de Souza Lacerda, L., de Souza Andrioli, A., Braz, W. R., Campos, L. M., de Paiva, M. R. B., Pittella, F., Fabri, R. L., & Tavares, G. D. (2025) · Fundamental & Clinical Pharmacology · doi:10.1111/fcp.70046 · Cited by 7 · see citing works
Hussein, H. M., Al-Khoury, D. K., Abdelnoor, A. M., & Rahal, E. A. (2019) · Scientific Reports · doi:10.1038/s41598-019-48282-2 · Cited by 6 · see citing works
Self-citationEffect of statin therapy on oral Candida carriage in hyperlipidemia patients: A pioneer study
Darwazeh, A., Al-Shorman, H., & Mrayan, B. (2022) · Dental and Medical Problems · doi:10.17219/dmp/142641 · Cited by 3 · see citing works
Haghani, I., Saeedi, M., Babaei, A., Yahyazadeh, Z., Hosseinnataj, A., Saravi, M. E., Akbari, F., Lotfizadeh, A., Visroodi, E. R., & Molania, T. (2024) · Journal of Prosthetic Dentistry · doi:10.1016/j.prosdent.2024.12.003 · Cited by 3 · see citing works
Neto, A. S. D. O., Amorim, M. E. S., Fabri, R. L., do Couto, R. O., & Araújo, M. G. D. F. (2025) · The Journal of Antibiotics · doi:10.1038/s41429-025-00848-1 · Cited by 1 · see citing works
EFFECT OF SIMVASTATIN ON THE GROWTH INHIBITION OF Candida albicans
Vieira, D. C. M., Vasconcelos, J. M., Alves, P. A. F., & Pereira, T. F. (2018) · Revista da Universidade Vale do Rio Verde · doi:10.5892/ruvrd.v16i1.4326
- Authors
- Rahal, E. A., Constantin, W. N., Zeidan, N., & Abdelnoor, A. M.
- Affiliations
- American University of Beirut (LB)
- Corresponding author
- Rahal, Elias A.
- ORCID
- Rahal, Elias A.
- Venue
- Frontiers in Microbiology
- Publisher
- Frontiers Media SA
- Published
- 2015-12-22
- Volume
- 6
- Pages
- 1474-1474
- ISSN
- 1664-302X (ISSN-L)
- PMC
- PMC4686692
- OpenAlex
- W2260059422
- Semantic Scholar
- feee4e410af20d9aed1a1a9ac02194a866f33861
- Cited by
- 14
- References
- 60
- Citations by year
- 2025: 3 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 3 · 2019: 2 · 2018: 2
- FWCI
- 0.52
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Microbiology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Conseil National de la Recherche Scientifique
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
- Keywords
- atorvastatin, statins, Candida albicans, fungal infection, immunosuppression, survival, interferon-gamma, IL-4, Th1/Th2 balance, antifungal therapy, BALB/c mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-06.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-06.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
