Neuroprotective Effect of Vitamin D on Behavioral and Oxidative Parameters of Male and Female Adult Wistar Rats Exposed to Mancozeb (manganese/zinc ethylene bis-dithiocarbamate).

The constant exposure of rural workers to pesticides is a serious public health problem. Mancozeb (MZ) is a pesticide  linked to hormonal, behavioral, genetic, and neurodegenerative effects, mainly related to oxidative stress. Vitamin D is a promising molecule that acts as a protector against brain aging. This study aimed to evaluate the neuroprotective role of vitamin D in adult male and female Wistar rats exposed to MZ. Animals received 40 mg/kg of MZ i.p. and 12.5 µg/kg or 25 µg/kg vitamin D by gavage, twice a week, for 6 weeks. The concentration of manganese had a significant increase in the hippocampus of both sexes and in the striatum of females, unlike zinc, which did not show a significant increase. MZ poisoning led to mitochondrial changes in brain tissues and promoted anxiogenic effects, especially in females. Alterations in antioxidant enzymes, mainly in the catalase activity were observed in intoxicated rats. Taken together, our results showed that exposure to MZ leads to the accumulation of manganese in brain tissues, and the behavior and metabolic/oxidative impairment were different between the sexes. Furthermore, the administration of Vitamin D was effective in preventing the damage caused by the pesticide.

Sex differences in subacute manganese intoxication: Oxidative parameters and metal deposition in peripheral organs of adult Wistar rats.

INTRODUCTION: Manganese (Mn) is an essential element required for several biological systems. However, it is toxic in excessive accumulation. The toxic effects following Mn overexposure is well known in the CNS but other studies evaluating other target tissues remain scarce. OBJECTIVE: This study aimed to investigate sex-related differences in oxidative stress, metabolic parameters and Mn deposition in peripheral organs of Wistar rats exposed to subacute model of intoxication. METHODS: Male and female adult Wistar rats received 6 or 15 mg/kg of MnCl2, intraperitoneally, 5 days a week, for 4 consecutive weeks to mimic subacute intoxication. Control group received sterile saline 0,9% following the same protocol. After this period, the metal accumulation, oxidative stress, mitochondrial activity and histological parameters in cardiac muscle, kidney, lungs and liver were analysed. RESULTS: Increased Mn concentrations were found in all organs, especially kidneys. The cardiac muscle analysis revealed increased lipid peroxidation and decreasing of GSH levels in both doses of Mn in male and female rats. The increase of lipid peroxidation in liver was more evident in the male group, and there was a significant decrease of antioxidant capacity in males' kidney. Nevertheless, there was an increase of mitochondrial complex I activity in kidney of females and increase of mitochondrial complex II activity in male group. Histological analysis revealed morphological changes in hepatic and pulmonary tissue. CONCLUSION: Taken together, our results showed that subacute Mn exposure lead to significant metabolic, biochemical alterations especially in kidney and liver. Nevertheless, despite Mn deposition was virtually the same in the peripheral organs of male and female rats, it promotes different toxic effects between sexes.