Amelioration of butylated hydroxytoluene against inorganic mercury induced cytotoxicity and mitochondrial apoptosis in PC12 cells via antioxidant effects
Amelioration of butylated hydroxytoluene against inorganic mercury induced cytotoxicity and mitochondrial apoptosis in PC12 cells via antioxidant effects
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DOI：
10.1016/j.fct.2020.111819
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发表时间：
2020-12-01
影响因子：
4.3
通讯作者：
Kurasaki, Masaaki
中科院分区：
文献类型：
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作者：
Hossain, Kaniz Fatima Binte;Hosokawa, Toshiyuki;Kurasaki, Masaaki
汞是一种有毒金属，因其对人类健康的危害而广为人知。丁基羟基甲苯(BHT)是一种酚类成分，通常用作食品添加剂和抗氧化剂。然而，BHT诱导的抗氧化性对重金属毒性的研究很少。我们假设BHT对汞诱导的细胞毒性有调节作用。本研究的目的是评价BHT对PC12细胞无机汞(IHG)毒性的保护作用。在PC12细胞中加入或不加入HgCl2(Hg2+)(5mU)和BHT(100mM)处理48h，并进一步分析。汞处理细胞后，细胞存活率下降、膜损伤、谷胱甘肽减少、DNA断裂、ROS生成，AKT、mTOR、ERK1、Nrf2和HO1的表达受到抑制，P53、Bax、细胞色素c和活性caspase3的表达增加。但BHT和Hg2+联合暴露可通过提高GSH含量、抑制ROS生成和氧化应激介导的损伤来保护Hg2+毒性。此外，BHT联合治疗通过增强促生存调节蛋白AKT、mTOR、ERK1、Nrf2和HO1来逆转促凋亡蛋白。这些发现证明，BHT通过增强谷胱甘肽和抗氧化剂，抑制Hg2+毒性，阻碍ROS的产生和内源性细胞凋亡；并提示BHT具有治疗作用。
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 mu M) and BHT (100 mu M) 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.