Protective Effects of Zinc Against Acute Arsenic Toxicity by Regulating Antioxidant Defense System and Cumulative Metallothionein Expression

Arsenic (As), a toxic metalloid, is one of the major global concerns. The toxicity resulting from As exposure is linked to the generation of reactive oxygen intermediates during their redox cycling and metabolic activation processes that cause lipid peroxidation (LPO). Zinc (Zn), a redox-inactive metal, helps to maintain cellular functions because of its prominent role in antioxidant network through multiple mechanisms. The present study, therefore, explores the effectiveness of administered Zn to combat against acute As toxicity by analysis of antioxidant defense status, alkaline phosphatase (ALP) activity, histological profile, MT expression, and elemental status in rat liver. To achieve this goal, four experimental groups, one control and three receiving different metal supplementations, were chosen (group 1, control; group 2, Zn supplemented; group 3, As substituted; group 4, Zn + As supplemented). The levels of reduced glutathione (GSH) and activities of glutathione reductase (GR) and ALP were lowered, whereas LPO levels and activity of superoxide dismutase (SOD) were elevated with no significant change in catalase (CAT) activity. Histopathological changes were also observed in the As substituted group in comparison to the control. Particle-induced X-ray emission (PIXE) analysis showed decrease in Fe and S concentration in rat liver after As intoxication, whereas As was below detection limit, i.e., < 1 ppm. Zn administration almost restored the antioxidants, ALP activity, histopathological changes, and elemental status. A cumulative increase in MT expression was found with the combined treatment of Zn and As. Also, Zn alone caused no significant change in the antioxidant defense system. It can be concluded that restoration of antioxidant activity and increased MT expression are the two independent protective mechanisms of Zn to reduce acute As toxicity.