Thymol, a monoterpene phenolic derivative of cymene, abrogates mercury-induced oxidative stress resultant cytotoxicity and genotoxicity in hepatocarcinoma cells

Environ Toxicol. 2015 Jul 8;30(8):968-80. doi: 10.1002/tox.21971. Epub 2014 Feb 27.

Abstract

Thymol (TOH) was investigated for its ability to protect against mercuric chloride (HgCl2 )-induced cytotoxicity and genotoxicity using human hepatocarcinoma (HepG2) cell line. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay confirmed the efficacy of TOH pretreatment in attenuating HgCl2 -induced cytotoxicity. Pretreatment with TOH inhibited HgCl2 -induced genotoxicity, depolarization of mitochondrial membrane, oxidative stress, and mitochondrial superoxide levels. Interestingly, TOH (100 µM) alone elevated the intracellular basal glutathione S-transferase (GST) levels and TOH pretreatment abrogated the decrease in glutathione, GST, superoxide dismutase, and catalase levels even after HgCl2 intoxication. Furthermore, TOH was also capable of inhibiting HgCl2 -induced apoptotic as well as necrotic cell death analyzed by flowcytometric analysis of cells dual stained with Annexin-FITC/propidium iodide. The present findings clearly indicate the cytoprotective potential of TOH against HgCl2 -induced toxicity, which may be attributed to its free radical scavenging ability which facilitated in reducing oxidative stress and mitochondrial damage thereby inhibiting cell death.

Keywords: apoptosis; genotoxicity; mercury; thymol.

MeSH terms

  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology*
  • Catalase / metabolism
  • Cell Line, Tumor
  • Cell Survival / drug effects*
  • Glutathione Transferase / metabolism
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology*
  • Membrane Potential, Mitochondrial / drug effects
  • Mercuric Chloride / antagonists & inhibitors*
  • Mercuric Chloride / toxicity*
  • Mitochondrial Membranes / drug effects
  • Mutagenicity Tests
  • Mutagens / toxicity*
  • Necrosis
  • Oxidative Stress / drug effects*
  • Protective Agents / pharmacology*
  • Superoxides / metabolism
  • Thymol / pharmacology*

Substances

  • Mutagens
  • Protective Agents
  • Superoxides
  • Thymol
  • Mercuric Chloride
  • Catalase
  • Glutathione Transferase