Selenium modulates inorganic mercury induced cytotoxicity and intrinsic apoptosis in PC12 cells.

Mercury (Hg) in its all forms, including inorganic Hg (iHg) is an environmental contaminant due to toxicity and diseases in human. However, a little is known about the underlying mechanisms responsible for iHg toxicity. Selenium (Se) is an essential trace element, recognized as an antioxidant and protective agent against metal toxicities. The purpose of this research was to investigate ameliorations of Se counter to iHg-mediated toxicity in PC12 cells. Cytotoxic assays have been shown that iHg (5 µM) caused oxidative stress and intrinsic apoptosis via ROS generation, oxidizing glutathione, damaging DNA, degrading cell membrane integrity, down-regulating mTOR, p-mTOR, akt and ERK1, and up-regulating cleaved caspase 3 and cytochrome c release in PC12 cells 48 h after incubation. Co-treatment of Se (5 µM) inhibited intrinsic apoptosis and oxidative stress induced by iHg (5 µM) via inhibiting ROS formation, boosting GPx contents, increasing reduced glutathione, limiting DNA degradation, improving cell membrane integrity, up-regulating mTOR, p-mTOR, akt, ERK1 and caspase 3, and down-regulating cleaved caspase 3 and cytochrome c leakage in PC12 cells. In conclusion, these results recommended that excessive ROS generation acts a critical role in iHg-influenced oxidative stress and co-treatment of Se attenuates iHg-cytotoxicity through its antioxidant properties.

Selenium and zinc protections against metal-(loids)-induced toxicity and disease manifestations: A review.

Metals are ubiquitous in the environment due to huge industrial applications in the form of different chemicals and from extensive mining activities. The frequent exposures to metals and metalloids are crucial for the human health. Trace metals are beneficial for health whereas non-essential metals are dangerous for the health and some are proven etiological factors for diseases including cancers and neurological disorders. The interactions of essential trace metals such as selenium (Se) and zinc (Zn) with non-essential metals viz. lead (Pb), cadmium (Cd), arsenic (As), and mercury (Hg) in biological system are very critical and complex. A huge number of studies report the protective role of Se and Zn against metal toxicity, both in animal and cellular levels, and also explain the numerous mechanisms involved. However, it has been considered that a tiny dyshomeostasis in the metals/trace metals status in biological system could induce severe deleterious effects that can manifest to numerous diseases. Thus, in this particular review, we have demonstrated the critical protection mechanism/s of Se and Zn against Cd, Pb, As and Hg toxicity in a one by one manner to clarify the up-to-date findings and perspectives. Furthermore, biomolecular consequences are comprehensively presented in light of particular cellular/biomolecular events which are somehow linked to a subsequent disease. The analyzed reports support significant protection potential of Se and Zn, either alone or in combination with other agents, against each of the abovementioned non-essential metals. However, Se and Zn are still not being used as detoxifying agents due to some unexplained reasons. We hypothesized that Se could be a potential candidate for detoxifying As and Hg regardless of their chemical speciations, but requires intensive clinical trials. However, particularly Zn-Hg interaction warrants more investigations both in animal and cellular level.