Fatemeh Shaki1, Sorour Ashari2, Nematollah Ahangar3. 1. Department of Toxicology/Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran. 2. Students Research Committee, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran. 3. Pharmaceutical Sciences Research Center and Department of Toxicology/Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran. Electronic address: n.ahangar@mazums.ac.ir.
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.
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.