Curcumin ameliorates mercuric chloride-induced liver injury via modulating cytochrome P450 signaling and Nrf2/HO-1 pathway

Ecotoxicol Environ Saf. 2021 Jan 15:208:111426. doi: 10.1016/j.ecoenv.2020.111426. Epub 2020 Oct 20.

Abstract

Environmental mercury is a concern for coastal ecosystem health, and exerts adverse effects on human health. Despite the growing body of evidence showing the hepatoprotective roles of curcumin on mercury, the knowledge between the macroscopic descriptions and the actual mechanism(s) underlying these processes is getting larger remains elusive. Herein, mice received single injection of mercuric chloride (HgCl2) (5 mg/kg body weight) and/or curcumin (50 mg/kg, body weight, p.o.). Firstly, the results showed curcumin could decline HgCl2-induced up-regulated the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Additionally, we also found that curcumin could suppress inflammatory damage, unbalance of trace elements (including sodium, magnesium, kalium, calcium overload), oxidative burst induced by HgCl2, which could be associated with cytochrome P450 (CYP450) signaling. Secondly, we found that curcumin could prevent HgCl2-induced cell death both in vivo and in vitro. Furthermore, curcumin significantly increased the nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) and consequently upregulated the expression of heme oxygenase 1 (HO-1) under HgCl2 treatment. Meanwhile, inhibition of HO-1 by zinc protoporphyria could abolish the cytoprotective effects of curcumin in HgCl2-treated L02 hepatocytes. In conclusion, our data identify that curcumin could enhance Nrf2-mediated HO-1 to upregulate antioxidant ability, which might be associate with CYP450 signaling to suppress liver damage induced by HgCl2. The present study further enriches and perfects the mechanism theory of HgCl2 toxicity and suggest that the CYP450 signaling and Nrf2/HO-1 pathway is important in shedding light on curcumin's hepatoprotective effects in HgCl2 toxicity.

Keywords: Curcumin; Cytochrome P450; Mercuric chloride; Nuclear factor E2-related factor 2; Trace elements.

MeSH terms

  • Alanine Transaminase / metabolism
  • Animals
  • Antioxidants / metabolism
  • Chemical and Drug Induced Liver Injury, Chronic / metabolism
  • Curcumin / pharmacology*
  • Cytochrome P-450 Enzyme System / metabolism*
  • Ecosystem
  • Hazardous Substances / toxicity*
  • Heme Oxygenase-1 / genetics
  • Hepatocytes / drug effects
  • Humans
  • Mercuric Chloride / toxicity*
  • Mice
  • NF-E2-Related Factor 2 / metabolism
  • Oxidation-Reduction
  • Oxidative Stress / drug effects
  • Protective Agents / pharmacology*
  • Signal Transduction / drug effects
  • Up-Regulation / drug effects

Substances

  • Antioxidants
  • Hazardous Substances
  • NF-E2-Related Factor 2
  • Protective Agents
  • Mercuric Chloride
  • Cytochrome P-450 Enzyme System
  • Heme Oxygenase-1
  • Alanine Transaminase
  • Curcumin