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Cited by 84Heavy Metal Exposure and ToxicityCoenzyme Q10 studies and effectsEnvironmental Toxicology and Ecotoxicology

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Coenzyme Q10 Activates the Antioxidant Machinery and Inhibits the Inflammatory and Apoptotic Cascades Against Lead Acetate-Induced Renal Injury in Rats

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AL-Megrin, Wafa A., Soliman, Doaa, Kassab, Rami B., Metwally, Dina M., Ahmed E. Abdel Moneim, El-Khadragy, Manal F.·2020·Frontiers in Physiology
DOI 10.3389/fphys.2020.00064PMC PMC7020615
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Abstract

The kidney is among the metabolic organs most susceptible to injury, particularly following exposure to xenobiotics and heavy metals. We aimed to explore the potential protective impacts of coenzyme Q10 (CoQ10) on lead acetate (PbAc)-induced nephrotoxicity in rats. Four experimental groups (n=7) were applied as follows: control group, CoQ10 alone (10 mg/kg), PbAc alone (20 mg/kg), and PbAc with CoQ10. Exposure to PbAc led to the accumulation of Pb in the kidney and increased urea and creatinine serum levels. The deposition of Pb coupled with the elevation of malondialdehyde and nitrate/nitrite levels along with the upregulation of inducible nitric oxide synthase. Additionally, upon PbAc poisoning, glutathione content and the antioxidant enzymes were depleted along with the downregulation of Nrf2 and HO-1 expression. Moreover, PbAc injection increased the protein and mRNA levels of pro-inflammatory cytokines namely, tumor necrosis factor-alpha and interleukin-1 beta, while decreased the levels of interleukin-10, an anti-inflammatory cytokine, in the kidney. Furthermore, exposure to PbAc correlated with increased levels of pro-apoptotic markers, Bax and caspase-3, and reduced levels of the anti-apoptotic marker Bcl-2. The administration of CoQ10 alleviated the molecular, biochemical and histological changes following PbAc intoxication. Thus, CoQ10 reduces the deleterious cellular side effects of PbAc exposure due to its antioxidant, anti-inflammatory and anti-apoptotic effects.

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FIGURE 1 Pb content in the renal tissue following treatment with PbAc (20 mg/kg) and/or CoQ10 (10 mg/kg). Results are presented as mean ± SD (n = 7). a indicates significant difference vs. the control group at P < 0.05; b indicates significant difference vs. the PbAc treated group at P < 0.05.
FIGURE 1 Pb content in the renal tissue following treatment with PbAc (20 mg/kg) and/or CoQ10 (10 mg/kg). Results are presented as mean ± SD (n = 7). a indicates significant difference vs. the control group at P < 0.05; b indicates significant difference vs. the PbAc treated group at P < 0.05.CC BY · PubMed Central
FIGURE 2 Levels of serum urea and creatinine following treatment with PbAc (20 mg/kg) and/or CoQ10 (10 mg/kg). Results are presented as mean ± SD (n = 7). a indicates significant difference vs. the control group at P < 0.05; b indicates significant difference vs. the PbAc treated group at P < 0.05.
FIGURE 2 Levels of serum urea and creatinine following treatment with PbAc (20 mg/kg) and/or CoQ10 (10 mg/kg). Results are presented as mean ± SD (n = 7). a indicates significant difference vs. the control group at P < 0.05; b indicates significant difference vs. the PbAc treated group at P < 0.05.CC BY · PubMed Central
FIGURE 3 Levels of oxidative stress markers in the renal tissue following treatment with PbAc (20 mg/kg) and/or CoQ10 (10 mg/kg). Results are presented as mean ± SD (n = 7). a indicates the significant difference vs. the control group at P < 0.05; b indicates significant difference vs. the PbAc treated group at P < 0.05.
FIGURE 3 Levels of oxidative stress markers in the renal tissue following treatment with PbAc (20 mg/kg) and/or CoQ10 (10 mg/kg). Results are presented as mean ± SD (n = 7). a indicates the significant difference vs. the control group at P < 0.05; b indicates significant difference vs. the PbAc treated group at P < 0.05.CC BY · PubMed Central
FIGURE 4 Activity and mRNA expression of the antioxidant enzymes in the renal tissue following treatment with PbAc (20 mg/kg) and/or CoQ10 (10 mg/kg). Activity of antioxidant enzymes are presented as mean ± SEM (n = 7). Real-time PCR results are figured as mean ± SD of triplicate assays and adjusted to Actb. a indicates significant difference vs. the control group at P < 0.05; b indicates significant difference vs. the PbAc treated group at P < 0.05.
FIGURE 4 Activity and mRNA expression of the antioxidant enzymes in the renal tissue following treatment with PbAc (20 mg/kg) and/or CoQ10 (10 mg/kg). Activity of antioxidant enzymes are presented as mean ± SEM (n = 7). Real-time PCR results are figured as mean ± SD of triplicate assays and adjusted to Actb. a indicates significant difference vs. the control group at P < 0.05; b indicates significant difference vs. the PbAc treated group at P < 0.05.CC BY · PubMed Central
FIGURE 5 mRNA and protein expression of Nrf2 and HO-1 in the renal tissue following treatment with PbAc (20 mg/kg) and/or CoQ10 (10 mg/kg). Real-time PCR findings are presented as mean ± SD of triplicate assays and referenced to Actb. a indicates significant difference vs. the control group at P < 0.05; b indicates significant difference vs. the PbAc treated group at P < 0.05.
FIGURE 5 mRNA and protein expression of Nrf2 and HO-1 in the renal tissue following treatment with PbAc (20 mg/kg) and/or CoQ10 (10 mg/kg). Real-time PCR findings are presented as mean ± SD of triplicate assays and referenced to Actb. a indicates significant difference vs. the control group at P < 0.05; b indicates significant difference vs. the PbAc treated group at P < 0.05.CC BY · PubMed Central
FIGURE 6 Levels and mRNA expression of tumor necrosis factor-α, interleukin-1β, interleukin-10 and inducible nitric oxide synthase mRNA expression in the renal tissue following treatment with PbAc (20 mg/kg) and/or CoQ10 (10 mg/kg). ELISA readings are presented as mean ± SD (n = 7). Real-time PCR results are presented as mean ± SD of triplicate assays and adjusted to Actb. a indicates significant difference vs. the control group at P < 0.05; b indicates significant difference vs. the PbAc treated group at P < 0.05.
FIGURE 6 Levels and mRNA expression of tumor necrosis factor-α, interleukin-1β, interleukin-10 and inducible nitric oxide synthase mRNA expression in the renal tissue following treatment with PbAc (20 mg/kg) and/or CoQ10 (10 mg/kg). ELISA readings are presented as mean ± SD (n = 7). Real-time PCR results are presented as mean ± SD of triplicate assays and adjusted to Actb. a indicates significant difference vs. the control group at P < 0.05; b indicates significant difference vs. the PbAc treated group at P < 0.05.CC BY · PubMed Central
FIGURE 7 Levels and mRNA expression levels of the apoptotic proteins (Bcl-2, Bax and caspases-3) in the renal tissue following treatment with PbAc (20 mg/kg) and/or CoQ10 (10 mg/kg). ELISA readings are presented as mean ± SD (n = 7). Real-time PCR results are presented as mean ± SEM of triplicate assays and adjusted to Actb. a indicates significant difference vs. the control group at P < 0.05; b indicates significant difference vs. the PbAc treated group at P < 0.05.
FIGURE 7 Levels and mRNA expression levels of the apoptotic proteins (Bcl-2, Bax and caspases-3) in the renal tissue following treatment with PbAc (20 mg/kg) and/or CoQ10 (10 mg/kg). ELISA readings are presented as mean ± SD (n = 7). Real-time PCR results are presented as mean ± SEM of triplicate assays and adjusted to Actb. a indicates significant difference vs. the control group at P < 0.05; b indicates significant difference vs. the PbAc treated group at P < 0.05.CC BY · PubMed Central
FIGURE 8 Light microscope photomicrographs of kidneys of rats treated with CoQ10 and lead acetate (PbAc) for 7 days. Cross sections of kidneys were stained with hematoxylin and eosin (400×). (a,b) kidneys from control and CoQ10 groups, respectively, exhibiting renal corpuscles (RC) with normal architecture of glomeruli (G) and urinary spaces. Note, normal structures of renal tubules consist of proximal tubules (PT) and distal tubules (DT). (c) kidney from PbAc-treated rat showing necrotic and shrunken glomeruli (arrowhead), and numerous inflammatory cells (star) in the interstitium. Most tubular cells showed pyknosis (right arrow), and are cloudy swelled (left arrow) with a small lumen of their tubules. (d) kidney from the post-treated group with CoQ10 against PbAc showing a glomerulus similar to normal (R) and also a lobulated glomerulus (LG). Most of the tubular cells have cloudy swelling with small or obstructed lumen (left arrow). There are few deeply eosinophilic cells representing necrotic cells (right arrow) and moderate inflammatory cells in the interstitial tissue (star).
FIGURE 8 Light microscope photomicrographs of kidneys of rats treated with CoQ10 and lead acetate (PbAc) for 7 days. Cross sections of kidneys were stained with hematoxylin and eosin (400×). (a,b) kidneys from control and CoQ10 groups, respectively, exhibiting renal corpuscles (RC) with normal architecture of glomeruli (G) and urinary spaces. Note, normal structures of renal tubules consist of proximal tubules (PT) and distal tubules (DT). (c) kidney from PbAc-treated rat showing necrotic and shrunken glomeruli (arrowhead), and numerous inflammatory cells (star) in the interstitium. Most tubular cells showed pyknosis (right arrow), and are cloudy swelled (left arrow) with a small lumen of their tubules. (d) kidney from the post-treated group with CoQ10 against PbAc showing a glomerulus similar to normal (R) and also a lobulated glomerulus (LG). Most of the tubular cells have cloudy swelling with small or obstructed lumen (left arrow). There are few deeply eosinophilic cells representing necrotic cells (right arrow) and moderate inflammatory cells in the interstitial tissue (star).CC BY · PubMed Central
FIGURE 9 A mechanistic diagram showing the protective effect of CoQ10 against PbAc-induced renal injury. Pb2+ triggered ROS generation in cytoplasm mediating oxidative reactions that led to the development of inflammatory and apoptotic events. However, CoQ10 prevented the renal injury following PbAc exposure through activating the Nrf2/HO-1 pathway and inhibiting the pro-inflammatory and pro-apoptotic molecules. Green line represents stimulatory and red line represents inhibitory effects.
FIGURE 9 A mechanistic diagram showing the protective effect of CoQ10 against PbAc-induced renal injury. Pb2+ triggered ROS generation in cytoplasm mediating oxidative reactions that led to the development of inflammatory and apoptotic events. However, CoQ10 prevented the renal injury following PbAc exposure through activating the Nrf2/HO-1 pathway and inhibiting the pro-inflammatory and pro-apoptotic molecules. Green line represents stimulatory and red line represents inhibitory effects.CC BY · PubMed Central

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Research works printed but not linked: 2

  1. Drury, 1980, Carleton’s Histological Techniques
  2. Luck, 1965, Catalase, Methods of Enzymatic Analysis, 855

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Metadata

Authors
AL-Megrin, W. A., Soliman, D., Kassab, R. B., Metwally, D. M., Moneim, A. E. A., & El-Khadragy, M. F.
Affiliations
  • Helwan University (EG)
  • Zagazig University (EG)
ORCID
Venue
Frontiers in Physiology
Publisher
Frontiers Media SA
Published
2020-02-07
Volume
11
Pages
64-64
ISSN
1664-042X (ISSN-L)
DOI
10.3389/fphys.2020.00064
PMC
PMC7020615
OpenAlex
W3004711026
Cited by
84
References
62
Citations by year
2026: 8 · 2025: 13 · 2024: 6 · 2023: 14 · 2022: 18 · 2021: 11 · 2020: 12
FWCI
5.50
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Physiology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Princess Nourah Bint Abdulrahman University
  • Deanship of Scientific Research, Princess Nourah Bint Abdulrahman University
Topics
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Heavy Metal Exposure and Toxicity
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Coenzyme Q10 studies and effects
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Environmental Toxicology and Ecotoxicology
Keywords
coenzyme Q10, lead acetate, nephrotoxicity, lead poisoning, kidney injury, oxidative stress, antioxidant enzymes, Nrf2, heme oxygenase-1, inflammatory cytokines, apoptosis, Bax, Bcl-2, caspase-3, glutathione, malondialdehyde, nitric oxide synthase

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