Molecular mechanisms underlying ameliorative impact of melatonin against age-dependent chronic arsenic toxicity in rats' brains.

Accumulation of random molecular damage such as oxidative DNA damage and inflammation is extremely found to be involved in the aging process. Due to extreme energy requirements and high lipid levels, the brain is more susceptible to oxidative damage during aging especially under exposure to toxic elements such as arsenic. Therefore, this study was aimed to evaluate the ameliorative effects of melatonin, as a neurohormone, on the arsenic-induced behavioral abnormalities, and the underlying mechanisms. Forty-eight rats, as young and old aged groups were exposed to 5.55 g/kg body weight arsenic for 4 weeks and then 10 mg/kg melatonin for 2 weeks. Our results showed that arsenic led to anxiety-like behavioral abnormalities in rats. Increased oxidative stress-induced damage to DNA, lipids and proteins, decreased potential of antioxidant defense system, induced apoptosis, elevated inflammation, and alteration in the histology of cortical region of brains are observed in the rats exposed to arsenic. These effects were more prominent in aged rats in comparison to young rats. Melatonin successfully attenuates arsenic induced adverse effects on the brain in both age groups. In conclusion, our study shows that melatonin has significant ameliorative impact on age-dependent cytotoxicity of arsenic in rats' brains.

Melatonin: a pleiotropic hormone as a novel potent therapeutic candidate in arsenic toxicity.

BACKGROUND: Arsenic is a natural element which exists in the environment in inorganic and organic forms. In humans, the main reason for the toxicity of arsenic is its uptake via water sources. As polluted water and the problems associated with it can be found in many countries. Therefore, considering all these positive effects of melatonin, this review is aimed at melatonin supplementation therapy on arsenic toxicity which seems to be a suitable therapeutic agent to eliminate the adverse effects of arsenic. METHODS AND RESULTS: It is seen in previous studies that chronic exposure to arsenic could cause serious dys functions of organs and induce different degrees of toxicities that is one of the first hazardous materials in the classification of substances by the United States Environmental Protection Agency so leads to costly cleanup operations burdening the economy. Arsenic harmfulness degree depends on the bioavailability, chemical form, valence state, detoxification, and metabolism of human body. The oxidative stress has a major role in arsenic-induced toxicity; on the other hand, it was discovered that melatonin is a powerful scavenger for free radical and it's an extensive-spectrum antioxidant. CONCLUSION: Due to its highly lipophilic and small size properties, melatonin accesses all intracellular organs by easily passing via the cell membrane and prevents protein, DNA damage, and lipid peroxidation. In particular, melatonin, by protecting and reducing oxidative stress in mitochondria, can normalize homeostasis and mitochondrial function and ultimately prevent apoptosis and cell death.

Attenuation of chronic arsenic neurotoxicity via melatonin in male offspring of maternal rats exposed to arsenic during conception: Involvement of oxidative DNA damage and inflammatory signaling cascades.

Prenatal exposure to arsenic is demonstrated to elevate the risk of brain damage and neurological disorders in the fetus, mainly due to its ability for crossing through the placental barriers. Increase in oxidative stress, inflammation, and DNA damage is main mechanisms of arsenic-induced neurotoxicity. Therefore, this study aimed to evaluate the neuroprotective effects of melatonin, as a potent anti-oxidant and anti-inflammatory agent against arsenic toxicity in the brains of male offspring rats. Pregnant mother rats were randomly assigned into four groups including group I, as control, group II received 10 mg/kg melatonin, group III received arsenic at 50 mg/kg, and group IV received melatonin and arsenic. After a two-month period, oxidative stress, DNA damage, inflammation and apoptosis were assessed in the male offspring rats. Exposure to arsenic significantly increased the pro-inflammatory and oxidative factors resulting in DNA damage and apoptosis in the brain tissues of offspring rats in comparison to controls (p < 0.05). Exogenous administration of melatonin showed a significant increase in the tissue levels of acetylcholine esterase, decrease in the lactate dehydrogenase and myeloperoxidase, when compared to arsenic group (p < 0.05). Melatonin also overcame the arsenic-induced oxidative stress and suppressed inflammation, DNA damage and apoptosis. Our results suggested that melatonin may be a promising neuro-protective agent and momentous therapy for the treatment of arsenic-toxicity in clinical conditions.