Melatonin reduces oxidative stress and increases gene expression in the cerebral cortex and cerebellum of aluminum‐exposed rats

Abstract

The pro-oxidant activity of aluminum (Al), the protective role of exogenous melatonin, as well as the mRNA levels of some antioxidant enzymes, were determined in cortex and cerebellum of rats following exposure to Al and/or melatonin. Two groups of male rats received intraperitoneal injections of Al lactate or melatonin at doses of 7 mg Al/kg/day and 10 mg/kg/day, respectively, for 11 wk. A third group of animals received concurrently Al lactate (7 mg Al/kg/day) plus melatonin (10 mg/kg/day) during the same period. A fourth group of rats was used as control. At the end of the treatment, the cerebral cortex and cerebellum were removed and processed to examine the following oxidative stress markers: glutathione transferase (GST), reduced glutathione (GSH), oxidized glutathione (GSSG), superoxide dismutase (SOD), glutathione reductase, glutathione peroxidase (GPx), catalase (CAT), thiobarbituric acid reactive substances (TBARS), as well as protein content. Moreover, gene expression of Cu-ZnSOD, MnSOD, GPx and CAT was evaluated by real-time RT-PCR. On the other hand, Al, Fe, Mn, Cu and Zn concentrations were determined in cortex and cerebellum of rats. Oxidative stress was promoted in both neural regions following Al administration, resulting from the pro-oxidant activity related with an increase in tissue Al concentrations. In contrast, melatonin exerted an antioxidant action which was related with an increase in the mRNA levels of the antioxidant enzymes evaluated. The results of the present investigation emphasize the potential use of melatonin as a supplement in the therapy of neurological disorders in which oxidative stress is involved.

Effects of U83836E on nerve functions, hyperalgesia and oxidative stress in experimental diabetic neuropathy

“…Vitamin C and E normalize antioxidant enzyme expression in diabetic rats (Sindhu et al, 2004). Melatonin, a potent antioxidant, has shown to produce an increase in antioxidant enzyme expression (Esparza et al, 2005). There might be possibility that U83836E enhance antioxidant enzyme expression, thereby increasing antioxidant enzyme levels and decrease the formation of free radicals leading to inhibition of lipid peroxidation.…”

Prooxidant effects of melatonin: a brief review

“…Generally speaking, melatonin provides protective cellular effects, especially for mitochondria, and it prevents the damage of proteins, lipids, and DNA (Zhang and Zhang, 2014). In vivo experiments pointed out that melatonin increases gene expression of multiple antioxidative genes in neuronal tissues, including those of CuZnSOD, MnSOD, GPx, catalase, and glutathione reductase (Kotler et al, 1998;Esparza et al, 2005;Gomez et al, 2005).…”

Iron-Mediated Inhibition of Mitochondrial Manganese Uptake Mediates Mitochondrial Dysfunction in a Mouse Model of Hemochromatosis

“…To determine whether liver mitochondria from the Hfe -/-mice exhibited increased oxidative damage, we determined the levels of thiobarbituric acid reactive substances (TBARS), a marker of non-specific lipid peroxidation (18)(19)(20). Liver mitochondria from Hfe -/-mice had a 61% increase in TBARS compared with controls ( Figure 1C; 0.132 ± 0.012 vs. 0.082 ± 0.01 nM malondialdehyde (MDA)/mg protein; P < 0.05).…”

“…Equal Thiobarbituric Acid Reactive Substances (TBARS) Assessment TBARS levels were measured to assess lipid peroxidation (18)(19)(20) according to the manufacturer's protocol (OXItek TBARS Assay Kit, Zeptometrix, Buffalo, NY, USA).…”