Thymoquinone alleviates arsenic induced hippocampal toxicity and mitochondrial dysfunction by modulating mPTP in...

Arsenic is a pervasive environmental pollutant that is found in ground waters globally and is related to numerous morbidities in the high-risk population areas in countries including Bangladesh, India, and the USA. Arsenic exposure has been ubiquitously reported for exacerbating free radical generation, mitochondrial dysfunction, and apoptosis by interfering with the mPTP functioning. Over the past decades, nutraceuticals with antioxidant properties have shown promising efficacy in arsenic poisoning. In the present study, we have examined, the protective efficacy of thymoquinone (TQ), an active component of seed oil of Nigella sativa with antioxidant and anti-inflammatory activity on arsenic-induced toxicity in hippocampi of Wistar rats. In our results, arsenic conditioning (10 mg/kg b.wt.; p.o.) for 8 days has caused a significant increase in intracellular ROS generation, mitochondrial dysfunction and apoptotic events. On the contrary pretreatment with TQ (2.5 and 5 mg/kg b.wt.; p.o.) inhibited arsenic-induced mitochondrial dysfunction such as lowering of mitochondrial membrane potential (Δψm). Our results indicated that the neuroprotective efficacy of TQ in arsenic-induced stress is mediated through or in part by inhibition of mPTP opening. Demonstration of neuroprotective action of TQ provides insight into the pathogenesis of arsenic-related neuropathological morbidities.