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

• Hossain, Kaniz Fatima Binte

• Hosokawa, Toshiyuki

• Saito, Takeshi

• Kurasaki, Masaaki

Abstract

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.

Journal

• Food and Chemical Toxicology

  Food and Chemical Toxicology 146 111819-, 2020-12

  Elsevier

Keywords

• Oxidative stress
• Intrinsic apoptosis
• Nrf2
• Heme oxygenege 1
• ERK1
• DNA fragmentation

Details

• CRID: 1050571782537238016
• NII Article ID: 120007173914
• NII Book ID: AA10627174
• DOI: 10.1016/j.fct.2020.111819
• HANDLE: 2115/83396
• ISSN: 02786915
• Web Site: https://api.elsevier.com/content/article/PII:S0278691520307092?httpAccept=text/xml
• Web Site: https://api.elsevier.com/content/article/PII:S0278691520307092?httpAccept=text/plain
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • Crossref
  • CiNii Articles
  • KAKEN