Amelioration of butylated hydroxytoluene against inorganic mercury induced cytotoxicity and mitochondrial apoptosis in PC12 cells via antioxidant effects

Mercury (Hg) is a toxic metal, well-known for its dangerous health effects on human. Butylated hydroxytoluene (BHT) is a phenolic component generally consumed as a food additive as an antioxidant. However, BHT induced antioxidant properties against heavy metals-influenced toxicity are little studied. We hypothesized that BHT has a regulatory effect on Hg-induced cytotoxicity. The objective of this research was to assess the protecting effects of BHT against inorganic Hg (iHg)-toxicity in PC12 cells, where cells were treated with/without HgCl2 (Hg2+) (5 μM) and BHT (100 μM) for 48 h and analyzed further. Cells treated by Hg caused a significant cell viability reduction, membrane damage, glutathione reduction, DNA fragmentation, ROS generation, with suppressed expressions of akt, mTOR, ERK1, Nrf2 and HO1; and elevated apoptotic expressions of p53, Bax, cytochrome c and active caspase 3. However, BHT and Hg2+ co-exposure showed prevention against Hg2+-toxicity by improving GSH content and inhibiting ROS generation and oxidative stress mediated damages. Additionally, BHT co-treatment inverted the pro-apoptotic proteins by augmenting pro-survival regulatory proteins akt, mTOR, ERK1, Nrf2 and HO1. These findings proved that BHT inhibits Hg2+-toxicity, hindering ROS generation and intrinsic apoptosis, via enhancing glutathione and antioxidants; and suggested BHT implications as therapeutic.