Melatonin attenuates diabetes‐induced oxidative stress in rabbits

Abstract

Oxidative stress is considered to be the main cause of diabetic complications. As the role of antioxidants in diabetes therapy is still underestimated, the aim of the present investigation was to study the antioxidative action of melatonin in comparison with N-acetylcysteine (NAC) under diabetic conditions. Alloxan-diabetic rabbits were treated daily with either melatonin (1 mg/kg, i.p.), NAC (10 mg/kg, i.p.) or saline. Blood glutathione redox state and serum hydroxyl free radicals (HFR), creatinine and urea levels were monitored. After 3 wk of treatment animals were killed and HFR content, reduced glutathione/oxidized glutathione (GSH/GSSG) ratio as well as the activities of glutathione reductase, glutathione peroxidase and gamma-glutamylcysteine synthetase were estimated in both liver and kidney cortex. Diabetes evoked a several-fold increase in HFR levels accompanied by a significant decline in GSH/GSSG ratio in serum and the examined organs. In contrast to NAC, melatonin (at 1/10 the dose of NAC) attenuated diabetes-induced alterations in glutathione redox state and HFR levels, normalized creatinine concentration and diminished urea content in serum. Moreover, the indole resulted in an increase in glutathione reductase activity in both studied organs and in a rise in glutathione peroxidase and gamma-glutamylcysteine synthetase activities in the liver. In contrast to NAC, melatonin seems to be beneficial for diabetes therapy because of its potent antioxidative and nephroprotective action. The indole-induced increase in the activities of the enzymes of glutathione metabolism might be of importance for antioxidative action of melatonin under diabetic conditions.

Melatonin prevents hyperglycemia in a model of sleep apnea

“…To the best of our knowledge, this is the first report of melatonin hav ing a role in preventing intermittent hypoxiarelated hyperglycemia. The protection conferred by melatonin against intermittenthypoxiatriggered hyperglycemia in the present study may be related either to its antioxidant role (23) or to the influence of melatonin on the con trol of carbohydrate metabolism (13,14,24). The pos sibility, however, that the antioxidant properties of melatonin are at play is overshadowed by the fact that the other antioxidant, Nacetylcysteine, had no ef fect on glucose levels or body weight.…”

“…Melatoninmediated protection against impairment or damage caused by intermittent hypoxia in diabetes may be related to the regulation of reactive oxygen species (13) and/or to influences of melatonin on insulin secretion (14). The antioxidant Nacetylcysteine, a precursor of Lcysteine, is a scavenger of reactive oxygen species (15) with a po tential to influence on certain aspects of the diabetes mechanisms (16,17).…”

Melatonin: An Established Antioxidant Worthy of Use in Clinical Trials

“…Melatonin also supports several intracellular enzymatic antioxidant enzymes, including SOD and glutathione peroxidase (GSH-Px) (63,64). Moreover, melatonin induces the activity of γ-glutamylcysteine synthetase, thereby stimulating the production of another intracellular antioxidant, glutathione (GSH) (65). A number of studies have shown that melatonin is significantly better than the classic antioxidants in resisting free-radical-based molecular destruction.…”

Comparison of the Efficacy of Melatonin and 1400W on Renal Ischemia/Reperfusion Injury: A Role for Inhibiting iNOS

“…Another possible explanation is that melatonin supports several intracellular antioxidant enzymes, including SOD and GSH-Px, [35,36] and induces the activity of glutamylcysteine ligase (GCL, formerly referred to as gamma-glutamylcysteine synthetase), thereby stimulating the production of another crucial intracellular antioxidant, glutathione. [37] In addition, melatonin has been shown to stimulate gene expression of SOD and GSH-Px. [22,33] Regarding the ameliorative effects of 1400W, there are conflicting data for both a beneficial and a harmful effect of NO on I/R injury.…”