Resveratrol protects against inorganic arsenic-induced oxidative damage and cytoarchitectural alterations in female mouse hippocampus

Abstract

Prolonged inorganic arsenic (iAs) exposure is widely associated with brain damage particularly in the hippocampus via oxidative and apoptotic pathways. Resveratrol (RES) has gained considerable attention because of its benefits to human health. However, its neuroprotective potential against iAs-induced toxicity in CA1 region of hippocampus remains unexplored.Therefore, we investigated the neuroprotective efficacy of RES against arsenic trioxide (As2O3)-induced adverse effects on neuronal morphology, apoptotic markers and oxidative stress parameters in mouse CA1 region (hippocampus).Adult female Swiss albino mice of reproductive maturity were orally exposed to either As2O3 (2 and 4 mg/kg bw) alone or in combination with RES (40 mg/kg bw) for a period of 45 days. After animal sacrifice on day 46, the perfusion fixed brain samples were used for the observation of neuronal morphology and studying the morphometric features. While the freshly dissected hippocampi were processed for biochemical estimation of oxidative stress markers and western blotting of apoptosis-associated proteins.Chronic iAs exposure led to significant decrease in Stratum Pyramidale layer thickness along with reduction in cell density and area of Pyramidal neurons in contrast to the controls. Biochemical analysis showed reduced hippocampal GSH content but no change in total nitrite (NO) levels following iAs exposure. Western blotting showed apparent changes in the expression levels of Bax and Bcl-2 proteins following iAs exposure, however the change was statistically insignificant. Contrastingly, iAs +RES co-treatment exhibited substantial reversal in morphological and biochemical observations.Together, these findings provide preliminary evidence of neuroprotective role of RES on structural and biochemical alterations pertaining to mouse hippocampus following chronic iAs exposure.