Mitochondrial oxidative stress and dysfunction in arsenic neurotoxicity: A review

Abstract

Arsenic is a toxic metalloid present ubiquitously on earth. Since the last decade, it has gained considerable attention due to its severe neurotoxic effects. Arsenic can cross the blood-brain barrier and accumulate in different regions of the brain suggesting its role in neurological diseases. Arsenic exposure has been associated with reactive oxygen species generation, which is supposed to be one of the mechanisms of arsenic-induced oxidative stress. Mitochondria, being the major source of reactive oxygen species generation may present an important target of arsenic toxicity. It is speculated that the proper functioning of the brain depends largely on efficient mitochondrial functions. Multiple studies have reported evidence of brain mitochondrial impairment after arsenic exposure. In this review, we have evaluated the proposed mechanisms of arsenic-induced mitochondrial oxidative stress and dysfunction. The understanding of molecular mechanism of mitochondrial dysfunction may be helpful to develop therapeutic strategies against arsenic-induced neurotoxicity. The ameliorative measures undertaken in arsenic-induced mitochondrial dysfunction have also been highlighted.

Heavy metals (Pb, Cd, As and MeHg) as risk factors for cognitive dysfunction: A general review of metal mixture mechanism in brain

“…In As related oxidative stress, the released ROS and lipid peroxidation elements increase the activity of SOD and decrease the glutathione-related enzymes, which lead to change in the cellular redox status (Rao and Avani, 2004). Biochemically, As mediated toxicity involves the induction of apopotic factors in the cerebral neurons by activating p38 mitogen-activated protein kinase (P 38 MAPK) and c-Jun N-terminal kinase 3 (JNK3) (Namgung and Xia, 2001), which enhances DNA damage and subsequently death of the brain cell (Felix et al, 2005) and resulting in impairments of neurobehavioral function (Prakash et al, 2015).…”

Comparative In Vitro Toxicity Evaluation of Heavy Metals (Lead, Cadmium, Arsenic, and Methylmercury) on HT-22 Hippocampal Cell Line

“…The sensitivity of As in different cell lines might be due to some underlying molecular mechanism [81]. Miller et al reported that As induces apoptosis in cell lines due to the generation of ROS [82], which enhances DNA damage [83] and subsequently the brain cell death [84] . In MeHg the apoptosis pattern was started at 0.18 µM and reached as sudden inflection at 0.29 µM (p *** < 0.05), however the percent of apoptotic cells are more than expected (47.6 ± 0.1); similar response was observed in human SH-SY 5Y neuroblastoma cells [85].…”

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“…The result of the present investigation demonstrated the adverse effect of arsenic treatment on female gonadal steroidogenesis and antioxidant defense mechanism 29 . In ovarian steroidogenesis 3 and 17 -HSDs are the key regulatory enzymes, the suppressed activities of these enzymes along with elevated cholesterol levels by arsenic suggest alteration in its hormone synthesis 27,30,31 . This is in agreement with the previous findings where arsenic treatment was associated with inhibition of ovarian steroidogenesis 27,32,33 .…”