Melatonin administration prevents the nephrotoxicity induced by gentamicin

Abstract

Objective To investigate the effect of melatonin on the antioxidant enzyme activity and renal tubular necrosis induced by gentamicin. Materials and methods Twenty-four adult male SpragueDawley rats were divided into three equal groups. In group 1, the rats were injected with vehicle (controls), in group 2 they were injected with gentamicin for 5 days and in group 3 injected with gentamicin plus melatonin for 5 days. At 24 h after the last injection, rats were killed and the renal cortex separated from the medulla. Most of the cortex was homogenized but a small sample was ®xed in formaldehyde solution for histological examination by light microscopy. Blood samples were also taken to assess the serum levels of urea, creatinine, Na + , K + and c-glutamyl transpeptidase (c-GT); before death, urine samples were analysed for protein content. Crude extracts of the cortex were used to determine lipoperoxides, reduced glutathione (GSH-Px), catalase and superoxide dismutase (SOD). The results were compared using the Mann±Whitney U-test.Results Compared with the controls rats, gentamicin caused hyperproteinuria, an increase in the level of c-GT in serum, a marked increase in lipoperoxides and a signi®cant decrease of GSH-Px, catalase and SOD activity in the kidney. In the rats in group 3 there was a marked restoration in lipid peroxidation, GSH-Px, catalase, SOD activity and proteinuria, and in c-GT in serum. In rats in group 2 there was widespread tubular necrosis (grade 2±4) but in rats in group 3 there was a marked reduction in the extent of tubular damage. There was no signi®cant difference in serum levels of Na + , K + , blood urea nitrogen and creatinine. Conclusion These results indicate that melatonin prevents the tubular necrosis induced by gentamicin in rats, presumably because it is a potent antioxidant and restores antioxidant enzyme activity in the rat kidney.

Melatonin Attenuates Colistin-Induced Nephrotoxicity in Rats

“…Melatonin (N-acetyl-5-methoxytryptamine) has been shown to abate the renal toxicity induced by a wide range of drugs that may cause oxidative stress in kidney cells, including gentamicin, amikacin, vancomycin, and cisplatin (5,36,38,43,44). A hormone secreted by the pineal gland, melatonin exhibits substantial antioxidant activity, especially as a scavenger of hydroxyl radicals (40,41).…”

“…Oxidative stress has been suggested to have a central role in nephrotoxicity caused by many drugs, including gentamicin; mitochondrial reactive oxygen species (ROS) are able to damage many cellular macromolecules (e.g., proteins and nucleic acids) which can lead to cell death (31). Considering the safety profile of melatonin (42,46) and its ability to reduce damage due to other nephrotoxic drugs (5,36,38,41,43,44), our study was designed to examine whether melatonin would protect against the nephrotoxicity of colistin.…”

“…Amelioration of the potential for nephrotoxicity would serve to widen the therapeutic window and allow administration of higher daily doses for increased exposure to colistin. Given that melatonin is a highly efficient free-radical scavenger that affords protection against the nephrotoxicity induced by a number of drugs (5,36,38,43,44), the present study was designed to investigate the potential protective effects of melatonin against colistin-induced renal toxicity. Colistin, rather than CMS, was used in the present study because it is the active antibacterial drug formed in the body after administration of CMS (4) and is substantially more toxic than CMS (15,17,21,35).…”

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“…An association between nephrotoxicity and oxidative stress has been confirmed in many experimental models 34,35,36 .…”

A novel approach to contrast-induced nephrotoxicity: the melatonergic agent agomelatine

“…The latest literature states that melatonin averts nephrotoxicity triggered by several drugs. [33][34][35][36][37][38] In particular, Gazi et al 39 demonstrated the defensive effect of melatonin administration in rat radiocontrast nephrotoxicity by reducing BUN and creatinine levels. 40 However, these studies have not measured oxidative and molecular parameters to indicate whether regeneration of the kidneys occurred after injury.…”