N-acetylcysteine elevates Nrf-2/ARE-regulated antioxidant response and mitochondrial biogenesis in different brain regions of monocrotophos exposed rats

Monocrotophos (MCP) is reported to induce the reactive oxygen species-mediated oxidative stress, which is supposed to be one of main mechanisms of MCP-induced neurotoxicity. The present study depicts the positive role of N-acetylcysteine (NAC) against oxidative damage via nuclear factor-erythroid factor 2-related factor 2 (Nrf-2) pathway and mitochondrial biogenesis in different brain regions of rat. Male Albino Wistar rats were divided into control, NAC-treated, MCP and NAC+MCP-treated groups. An intragastric dose of MCP (0.9 mg/kg b.wt) and NAC (200 mg/kg b.wt) was administered for 28 days. Results showed that MCP significantly decreased the activities of mitochondrial complexes, altered the gene expression of Nrf-2/ARE-mediated phase-II detoxifying enzymes and mitochondrial biogenesis factors (peroxiredoxin 1, glutamate-cysteine ligase catalytic subunit, heme oxygenase, NAD(P)H: quinine oxidoreductase 1, peroxisome proliferator-activated receptor gamma coactivator 1-alpha, mitochondrial transcription factor A, nuclear respiratory factors-1 and -2 and manganese superoxide dismutase). The co-administration of NAC modulated these altered mitochondrial biochemicals, restored the gene expressions of phase-II enzymes and mitochondrial biogenesis factors in different regions of rats' brain. The finding of the present study suggest that NAC administration might protect against the MCP-induced neurotoxicity in rodents.