Melatonin can attenuate ciprofloxacin induced nephrotoxicity: Involvement of nitric oxide and TNF-α
Abstract
Background Ciprofloxacin is a synthetic broad-spectrum antimicrobial agent of fluoroquinolone family. The aim of our investigation was to evaluate the role of oxidative damage and inflammation in nephrotoxic potential of Ciprofloxacin and protective effects of melatonin against its nephrotoxicity in male Wistar rats.Methods The animals were divided into six groups: Control, ciprofloxacin (100mg/kg/day, i.p), ciprofloxacin with three doses (2.5, 5 and 10mg/kg/day) of melatonin and a group which received ciprofloxacin (100mg/kg/day) plus vitamin E (100mg/kg/day) for 8 consecutive days. 24h after last injection, the animals were euthanized and kidney tissues were separated. Finally reactive oxygen species, glutathione content, lipid peroxidation, protein carbonyl, nitric oxide and TNF-α were evaluated. Also, pathological examination and measuring of kidney biochemical markers (BUN and Cr) were done.Results The administration of ciprofloxacin for 8days resulted in significant increase (P<0.01) in kidney biomarkers (BUN and Cr) and pathological changes. Also, Oxidative stress was evident in ciprofloxacin group by significantly (p<0.001) increased reactive oxygen species, lipid peroxidation and protein carbonyl level and decreased glutathione content (p<0.001). Increased in inflammation process was shown by increase in NO and TNF-α (P<0.001). Administration of melatonin was able to protect against deterioration in nephrotoxic markers and suppressed the increase in oxidative stress and inflammatory markers.Conclusion Our study showed the critical role of oxidative damage and inflammation in ciprofloxacin-induced nephrotoxicity that markedly inhibited by administration of melatonin. So, melatonin can be suggested for prevention of ciprofloxacin-induced nephrotoxicity.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
Melatonin may offset the toxicity of certain drugs through its antioxidant activity.
“While there are many reasons to be concerned about interactions, there may also be a role for melatonin to offset the toxicity of certain drugs through its antioxidant activity [307,308].”
From Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements (2022) · cites this paper as [308]
Cites
Bradford, M. M. (1976) · Analytical Biochemistry · doi:10.1016/0003-2697(76)90527-3 · Cited by 255,302 · see citing works
Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids
Green, L. C., Wagner, D. A., Glogowski, J. A., Skipper, P. L., Wishnok, J. S., & Tannenbaum, S. R. (1982) · Analytical Biochemistry · doi:10.1016/0003-2697(82)90118-x · Cited by 12,061 · see citing works
Nitric Oxide and Peroxynitrite in Health and Disease
Pacher, P., Beckman, J. S., & Liaudet, L. (2007) · Physiological Reviews · doi:10.1152/physrev.00029.2006 · Cited by 6,390 · see citing works
Protein carbonyl groups as biomarkers of oxidative stress
Dalle‐Donne, I., Rossi, R., Giustarini, D., Milzani, A., & Colombo, R. (2003) · Clinica Chimica Acta · doi:10.1016/s0009-8981(03)00003-2 · Cited by 2,353 · see citing works
Regulation of antioxidant enzymes: a significant role for melatonin
Rodrı́guez, C., Mayo, J. C., Sainz, R. M., Antolı́n, I., Herrera, F., Martı́n, V., & Reiter, R. J. (2003) · Journal of Pineal Research · doi:10.1046/j.1600-079x.2003.00092.x · Cited by 1,990 · see citing works
Melatonin : a potent, endogenous hydroxyl radical scavenger
Tan, D. (1993) · Endocrine Journal · Cited by 1,659 · see citing works
Free radicals and antioxidants in human health: current status and future prospects.
Devasagayam, T. P. A., Tilak, J. C., Boloor, K. K., Sane, K. S., Ghaskadbi, S., & Lele, R. D. (2004) · PubMed · Cited by 1,563 · see citing works
Azithromycin and the Risk of Cardiovascular Death
Ray, W. A., Murray, K. T., Hall, K., Arbogast, P. G., & Stein, C. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1003833 · Cited by 958 · see citing works
LIPID PEROXIDATION, OXYGEN RADICALS, CELL DAMAGE, AND ANTIOXIDANT THERAPY
Halliwell, B. B., & Gutteridge, J. C. (1984) · The Lancet · doi:10.1016/s0140-6736(84)91886-5 · Cited by 796 · see citing works
Wolfson, J. S., & Hooper, D. C. (1985) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.28.4.581 · Cited by 700 · see citing works
Intracellular Antioxidants: from Chemical to Biochemical Mechanisms
Chaudière, J., & Ferrari-Iliou, R. (1999) · Food and Chemical Toxicology · doi:10.1016/s0278-6915(99)00090-3 · Cited by 671 · see citing works
Nanotoxicity: An Interplay of Oxidative Stress, Inflammation and Cell Death
Khanna, P., Ong, C., Bay, B., & Baeg, G. H. (2015) · Nanomaterials · doi:10.3390/nano5031163 · Cited by 582 · see citing works
Free Radical‐Mediated Molecular Damage
Reiter, R. J., Acuña-Castroviejo, D., Tan, D. X., & Burkhardt, S. (2001) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2001.tb03627.x · Cited by 398 · see citing works
Gentamicin-induced nephrotoxicity: Do we have a promising therapeutic approach to blunt it?
Balakumar, P., Rohilla, A., & Thangathirupathi, A. (2010) · Pharmacological Research · doi:10.1016/j.phrs.2010.04.004 · Cited by 321 · see citing works
Fluoroquinolone prescribing in the United States: 1995 to 2002
Linder, J. A., Huang, E. S., Steinman, M. A., Gonzales, R., & Stafford, R. S. (2005) · The American Journal of Medicine · doi:10.1016/j.amjmed.2004.09.015 · Cited by 309 · see citing works
Valenzuela, A. (1991) · Life Sciences · doi:10.1016/0024-3205(91)90550-u · Cited by 291 · see citing works
The Use of Antibiotics: A Clinical Review of Antibacterial, Antifungal And Antiviral Drugs
Kucers, A. (1997) · Cited by 269 · see citing works
Gilad, E., Wong, H. R., Zingarelli, B., Virág, L., O'connor, M., Salzman, A. L., & Szabó, C. (1998) · The FASEB Journal · doi:10.1096/fasebj.12.9.685 · Cited by 252 · see citing works
Nitric oxide induces apoptosis via triggering mitochondrial permeability transition
Hortelano, S., Dallaporta, B., Zamzami, N., Hirsch, T., Susín, S. A., Marzo, I., Boscá, L., & Kroemer, G. (1997) · FEBS Letters · doi:10.1016/s0014-5793(97)00623-6 · Cited by 234 · see citing works
Protective effect of lycopene on gentamicin-induced oxidative stress and nephrotoxicity in rats
Karahan, İ., Ateşşahín, A., Yılmaz, S., Çeribaşı, A. O., & Sakın, F. (2005) · Toxicology · doi:10.1016/j.tox.2005.07.007 · Cited by 214 · see citing works
Free Radicals and Other Reactive Species in Disease
Halliwell, B. B. (2005) · Encyclopedia of Life Sciences · doi:10.1038/npg.els.0003913 · Cited by 187 · see citing works
Singh, R. P., Tyagi, A. K., Dhanalakshmi, S., Agarwal, R., & Agarwal, C. (2003) · International Journal of Cancer · doi:10.1002/ijc.11620 · Cited by 185 · see citing works
Cell Signaling in Oxidative Stress-Induced Liver Injury
Czaja, M. J. (2007) · Seminars in Liver Disease · doi:10.1055/s-2007-991514 · Cited by 158 · see citing works
Toxicity of depleted uranium on isolated rat kidney mitochondria
Shaki, F., Hosseini, M., Ghazi‐Khansari, M., & Pourahmad, J. (2012) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2012.08.015 · Cited by 156 · see citing works
Self-citationReaction mechanism of melatonin oxidation by reactive oxygen species in vitro
Bonnefont‐Rousselot, D., Collin, F., Jore, D., & Gardès-Albert, M. (2011) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2010.00847.x · Cited by 148 · see citing works
Pedraza‐Chaverrí, J., Barrera, D., Maldonado, P. D., Chirino, Y. I., Macías-Ruvalcaba, N. A., Medina‐Campos, O. N., Castro, L., Salcedo, M. I., & Hernández‐Pando, R. (2004) · BMC Clinical Pharmacology · doi:10.1186/1472-6904-4-5 · Cited by 144 · see citing works
Zhang, F., Xu, Z., Gao, J., et al. (2008) · Environmental Toxicology and Pharmacology · doi:10.1016/j.etap.2008.04.003 · Cited by 138 · see citing works
Hortelano, S., Alvarez, A. M., & Boscá, L. (1999) · The FASEB Journal · doi:10.1096/fasebj.13.15.2311 · Cited by 133 · see citing works
Mechanisms of Nitric Oxide-Dependent Apoptosis: Involvement of Mitochondrial Mediators
Boscá, L. (1999) · Cellular Signalling · doi:10.1016/s0898-6568(98)00064-3 · Cited by 128 · see citing works
Hara, M., Yoshida, M., Nishijima, H., Yokosuka, M., Iigo, M., Ohtani‐Kaneko, R., Shimada, A., Hasegawa, T., Akama, Y., & Hirata, K. (2001) · Journal of Pineal Research · doi:10.1034/j.1600-079x.2001.300301.x · Cited by 113 · see citing works
Risk of acute kidney injury associated with the use of fluoroquinolones
Bird, S. T., Etminan, M., Brophy, J. M., et al. (2013) · Canadian Medical Association Journal · doi:10.1503/cmaj.121730 · Cited by 90 · see citing works
Guevara, J. R. V., Bonilla, E., Chacín‐Bonilla, L., Mora, M., Medina-Leendertz, S., & Bravo, Y. (2014) · Acta Tropica · doi:10.1016/j.actatropica.2014.04.021 · Cited by 88 · see citing works
Hortelano, S., Castilla, M., Torres, A. M., et al. (2000) · Journal of the American Society of Nephrology · doi:10.1681/asn.v11122315 · Cited by 87 · see citing works
Melatonin attenuates gentamicin-induced nephrotoxicity and oxidative stress in rats
Lee, I.-C., Kim, S., Lee, S., et al. (2012) · Archives of Toxicology · doi:10.1007/s00204-012-0849-8 · Cited by 78 · see citing works
Fluoroquinolone-Induced Renal Failure
Lomaestro, B. M. (2000) · Drug Safety · doi:10.2165/00002018-200022060-00006 · Cited by 78 · see citing works
Inhibition of pancreatic cholesterol esterase reduces cholesterol absorption in the hamster
Heidrich, J. E., Contos, L. M., Hunsaker, L. A., et al. (2004) · BMC Pharmacology · doi:10.1186/1471-2210-4-5 · Cited by 76 · see citing works
Tumor necrosis factor-α in cisplatin nephrotoxicity: A homebred foe?
Dong, Z., & Atherton, S. S. (2007) · Kidney International · doi:10.1038/sj.ki.5002320 · Cited by 66 · see citing works
Wu, Q., Jing, Y., Yuan, X., Zhang, X., Li, B., Liu, M., Wang, B., Li, H., Liu, S., & Xiu, R. (2014) · Journal of Molecular Neuroscience · doi:10.1007/s12031-014-0430-4 · Cited by 62 · see citing works
Majsterek, I., Gloc, E., Błasiak, J., et al. (2005) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2005.00197.x · Cited by 59 · see citing works
Ciprofloxacin overdose: Acute renal failure with prominent apoptotic changes
Dharnidharka, V., Nadeau, K., Cannon, C. L., et al. (1998) · American Journal of Kidney Diseases · doi:10.1053/ajkd.1998.v31.pm9531191 · Cited by 56 · see citing works
Update on the diagnosis and management of acute kidney injury
Edelstein, C. (2010) · International Journal of Nephrology and Renovascular Disease · doi:10.2147/ijnrd.s8641 · Cited by 50 · see citing works
Ahmadiasl, N., Banaei, S., Alihemmati, A., et al. (2013) · PubMed · doi:10.5681/apb.2014.008 · Cited by 42 · see citing works
Pouzaud, F., Dutot, M., Martin, C., et al. (2006) · Comparative Biochemistry and Physiology Part C Toxicology & Pharmacology · doi:10.1016/j.cbpc.2006.02.006 · Cited by 33 · see citing works
Kumar, U., Chen, J., Sapoznikhov, V., et al. (2005) · Clinical and Experimental Hypertension · doi:10.1081/ceh-200044249 · Cited by 30 · see citing works
Mahmoud, A. M., Germoush, M. O., & Soliman, A. S. (2014) · International Journal of Pharmacology · doi:10.3923/ijp.2014.451.460 · Cited by 29 · see citing works
Olayinka, E. T., Ore, A., & Ola, O. S. (2015) · Advances in Toxicology · doi:10.1155/2015/385023 · Cited by 23 · see citing works
Raja, N., Miller, W., McMillan, R., et al. (1998) · Bone Marrow Transplantation · doi:10.1038/sj.bmt.1701256 · Cited by 20 · see citing works
Safety study of Ciprofloxacin in newborn mice
Bourgeois, T., Delezoide, A., Zhao, W., et al. (2015) · Regulatory Toxicology and Pharmacology · doi:10.1016/j.yrtph.2015.11.002 · Cited by 20 · see citing works
Effects Of Ciprofloxacin And Levofloxacin Administration On Some Oxidative Stress Markers In The Rat
Afolabi, O. K., & Oyewo, E. B. (2014) · Zenodo (CERN European Organization for Nuclear Research) · doi:10.5281/zenodo.1090855 · Cited by 20 · see citing works
Ore, A., & Olayinka, E. T. (2015) · Biochemistry Research International · doi:10.1155/2015/192724 · Cited by 19 · see citing works
Effects of some quinolone antibiotics on malondialdehyde levels and catalase activity in chicks
Altınordulu, Ş., & Eraslan, G. (2009) · Food and Chemical Toxicology · doi:10.1016/j.fct.2009.08.018 · Cited by 18 · see citing works
Ciprofloxacin-induced renal insufficiency in cystic fibrosis
Moffett, B. S., Rosenstein, B. J., & Mogayzel, P. J. (2003) · Journal of Cystic Fibrosis · doi:10.1016/s1569-1993(03)00059-6 · Cited by 16 · see citing works
André, M., Latado, H., & Felley‐Bosco, E. (2004) · Biochemical Pharmacology · doi:10.1016/j.bcp.2004.11.007 · Cited by 15 · see citing works
Waddington, S. N., Mosley, K., & Cattell, V. (1999) · Clinical & Experimental Immunology · doi:10.1046/j.1365-2249.1999.01049.x · Cited by 12 · see citing works
Sureshkumar, V., Sarathchandra, G., & Ramesh, J. (2013) · Veterinary World · doi:10.14202/vetworld.2013.668-673 · Cited by 11 · see citing works
Olayinka, E. T. (2014) · Journal of Pharmaceutical Research International · doi:10.9734/bjpr/2014/3853 · Cited by 11 · see citing works
Effects of Ciprofloxacin and Levofloxacin Administration on some oxidative stress markers in the rat
Afolabi, O. K., & Oyewo, E. B. (2013) · Zenodo (CERN European Organization for Nuclear Research) · doi:10.5281/zenodo.2659270 · Cited by 11 · see citing works
(2020) · Journal of Nephropathology · doi:10.5812/jnp · Cited by 7 · see citing works
Olayinka, E. T., Ore, A., & Adeyemo, O. A. (2015) · Journal of Pharmaceutical Research International · doi:10.9734/bjpr/2015/16210 · Cited by 4 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Minich, D. M., Henning, M., Darley, C., Fahoum, M., Schuler, C. B., & Frame, J. (2022) · Nutrients · doi:10.3390/nu14193934 · Cited by 176 · see citing works
Pleiotropic Effects of Melatonin
Mahmood, D. (2019) · Drug Research · doi:10.1055/a-0656-6643 · Cited by 52 · see citing works
Melatonin ameliorates the drug induced nephrotoxicity: Molecular insights
Raza, Z., & Naureen, Z. (2020) · Nefrología · doi:10.1016/j.nefro.2019.06.009 · Cited by 43 · see citing works
- Authors
- Shaki, F., Ashari, S., & Ahangar, N.
- Affiliations
- Mazandaran University of Medical Sciences (IR)
- Corresponding author
- Ahangar, Nematollah
- Venue
- Biomedicine & Pharmacotherapy
- Publisher
- Elsevier BV
- Published
- 2016-12
- Volume
- 84
- Pages
- 1172-1178
- ISSN
- 0753-3322 (ISSN-L)
- OpenAlex
- W2542816832
- Cited by
- 30
- References
- 59
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 1 · 2023: 3 · 2022: 4 · 2021: 3 · 2020: 3 · 2019: 4 · 2018: 3 · 2017: 3
- FWCI
- 3.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Biomedicine & Pharmacotherapy (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Mazandaran University of Medical Sciences (1727.2015)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Chemotherapy-induced organ toxicity mitigation
- Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Keywords
- melatonin, ciprofloxacin, nephrotoxicity, fluoroquinolones, oxidative stress, nitric oxide, TNF-α, inflammation, lipid peroxidation, protein carbonyls, glutathione, vitamin E, kidney injury, renal biomarkers
- MeSH terms
- Animals, Ciprofloxacin, Creatinine, Glutathione, Kidney, Kidney Diseases, Kidney Function Tests, Male, Melatonin, Nitric Oxide, Tumor Necrosis Factor-alpha, Lipid Peroxidation, Rats, Wistar, Reactive Oxygen Species, Protein Carbonylation
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.
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