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Melatonin protects against gentamicin-induced nephrotoxicity in rats
Göksel Sener1, A Ozer Sehirli, Hale Z Altunbas
1Department of Pharmacology, School of Pharmacy, Marmara University, Istanbul, Turkey. gokselsener@hotmail.com
Abstract:
Acute renal failure is a major complication of gentamicin (GEN), which is widely used in the treatment of gram-negative infections. A large body of in vitro and in vivo evidence indicates that reactive oxygen metabolites (or free radicals) are important mediators of gentamicin nephrotoxicity. In this study we investigated the role of free radicals in gentamicin-induced nephrotoxicity and whether melatonin, a potent antioxidant could prevent it. For this purpose female Sprague-Dawley rats were given intraperitoneally either gentamicin sulphate (40 mg/kg), melatonin (10 mg/kg), gentamicin plus melatonin or vehicle (control) twice daily for 14 days. The rats were decapitated on the 15th day and kidneys were removed. Blood urea nitrogen (BUN) and creatinine levels were measured in the blood and malondialdehyde (MDA) and glutathione (GSH) levels, protein oxidation (PO) and myeloperoxidase (MPO) activity were determined in the renal tissue. Gentamicin was observed to cause a severe nephrotoxicity which was evidenced by an elevation of BUN and creatinine levels. The significant decrease in GSH and increases in MDA levels, PO and MPO activity indicated that GEN-induced tissue injury was mediated through oxidative reactions. On the other hand simultaneous melatonin administration protected kidney tissue against the oxidative damage and the nephrotoxic effect caused by GEN treatment.
Insights
Gentamicin causes kidney damage through oxidative stress. Melatonin, a potent antioxidant, effectively protected against this gentamicin-induced nephrotoxicity in rats.
Area of Science:
- Nephrology
- Toxicology
- Biochemistry
Background:
- Gentamicin (GEN) is crucial for treating gram-negative infections but can cause acute renal failure.
- Reactive oxygen species (free radicals) are implicated as key mediators in gentamicin nephrotoxicity.
- Melatonin is recognized for its potent antioxidant properties.
Purpose of the Study:
- To investigate the role of free radicals in gentamicin-induced nephrotoxicity.
- To determine if melatonin can prevent gentamicin-induced kidney damage.
Main Methods:
- Female Sprague-Dawley rats received intraperitoneal injections of gentamicin, melatonin, or both for 14 days.
- Kidney tissues and blood were analyzed for biomarkers of renal function and oxidative stress.
- Measurements included blood urea nitrogen (BUN), creatinine, malondialdehyde (MDA), glutathione (GSH), protein oxidation (PO), and myeloperoxidase (MPO) activity.
Main Results:
- Gentamicin administration significantly elevated BUN and creatinine levels, indicating severe nephrotoxicity.
- Increased MDA, PO, and MPO activity, along with decreased GSH levels, confirmed oxidative damage in renal tissue.
- Co-administration of melatonin mitigated the oxidative damage and protected kidney tissue from gentamicin's toxic effects.
Conclusions:
- Gentamicin-induced nephrotoxicity is mediated by oxidative stress.
- Melatonin demonstrates a protective effect against gentamicin-induced kidney damage.
- Melatonin holds potential as a therapeutic agent to prevent gentamicin nephrotoxicity.