Melatonin treatment against remote organ injury induced by renal ischemia reperfusion injury in diabetes mellitus

Abstract

Oxidative stress may have a role in liver damage after acute renal injury due to various reasons such as ischemia reperfusion (IR). Diabetes mellitus (DM) is an important disease for kidneys and may cause nephropathy as a long term complication. The aim of this study was to investigate protective effect of melatonin, a potent antioxidant, against distant organ injury on liver induced by renal IR in rats with or without DM. The rats were divided into six groups: control (n=7), DM (n=5), IR (n=7), DM+IR (n=7), melatonin+IR (Mel+IR) (melatonin, 4 mg/ kg during 15 days) (n=7), and Mel+DM+IR groups (n=7). Diabetes developed 3 days after single i.p. dose of 45 mg/kg streptozotocin. After 15 day, the left renal artery was occluded for 30 min followed 24 h of reperfusion in IR performed groups. DM did not alter oxidative parameters alone in liver tissue. The levels of malondialdehyde, protein carbonyl and nitric oxide with activities of xanthine oxidase and myeloperoxidase were increased in liver tissues of diabetic and non-diabetic IR groups. Nitric oxide level in DM was higher than control. The activities of catalase and superoxide dismutase were increased in IR groups in comparison with control and DM. ALT and AST levels were higher in IR and DM+IR groups than control and DM. Melatonin treatment reversed all these oxidant and antioxidant parameters to control values as well as serum liver enzymes. We concluded that renal IR may affect distant organs such as liver and oxidative stress may play role on this injury, but DM has not an effect on kidney induced distant organ injury via oxidant stress. Also, it was concluded that melatonin treatment may prevent liver oxidant stress induced by distant injury of kidney IR.

Melatonin ameliorates oxidative damage in hyperglycemia-induced liver injury

“…Superoxide (O2), hydroxyl anion (OH), hydrogen peroxides (H 2 O 2 ) or singlet oxygen (O 2 ) could initiate the cascade, resulting in the production of MDA. e increase in TBARS associated with diabetes is prevented by treatment with melatonin [5][6][7][8], if this treatment is given before or immediately a er the diabetogen. In the present study, the hypothesis that melatonin ameliorates oxidative damage in STZ-induced liver injury was tested.…”

“…In the current study, a blood glucose level over 200 mg/dl was considered indicative of diabetes. Although lipid peroxidation markers have been well studied in diabetes [5][6][7][8]14,15], there have been only a few studies of hyperglycemia-induced plasma protein, thiol and 8-OHdG levels.…”

“…In addition, melatonin also indirectly enhances the levels of potential antioxidants such as glutathione peroxidase, superoxide dismutase (SOD) and glutathione (GSH) [3,4]. Numerous experimental and clinical studies suggest that daily melatonin supplementation may be bene cial for the treatment of diabetes [5][6][7][8]. Since there is insu cient knowledge on the bene cial role of melatonin in the reversal/prevention of oxidative DNA damage in diabetes, the present study has been undertaken.…”

Hypoglycaemic and Hypolipidemic Effects of Polyherbal Formulation in Streptozotocin-Induced Diabetic Rats.

“…The most commonly used drug for this induction is Streptozotocin (STZ) because of its toxic effects on islet beta cells (Fadillioglu et al, 2008). (Rakieten et al, 1963; Ar'Rajab and Ahrén 1993; Gu et al, 1997).…”

Beneficial effects of melatonin on acetylsalicylic acid induced liver damage in rats

“…Melatonin also indirectly activates antioxidative enzyme productions, reduces lipid oxidation and regulates gene expression of several protective enzymes such as Cu/Zn superoxide dismutase (CuZn SOD) and Mn superoxide dismutase [16][17][18]. In addition, the metabolites of melatonin are even more effective antioxidants than melatonin during oxidative stress and inflammatory pathways [19,20].…”