Antioxidant, antiapoptotic, antigenotoxic, and hepatic ameliorative effects of L-carnitine and selenium on cadmium-induced hepatotoxicity and alterations in liver cell structure in male mice

Ecotoxicol Environ Saf. 2019 May 30:173:419-428. doi: 10.1016/j.ecoenv.2019.02.041. Epub 2019 Feb 21.

Abstract

L-carnitine (LC) and selenium (Se) have significant protective and antioxidant effects on several tissues. Cadmium (Cd), widely used in some industries and emitted from fossil fuels, is a heavy metal having a number of side effects, including hepatotoxicity. This study aims to assess the ameliorative function of both LC and SeCl4 on cadmium chloride (CdCl2)-induced liver toxicity. In total, 70 male mice included in this study were allocated to seven groups: control, CdCl2, LC, SeCl4, CdCl2 plus SeCl4, CdCl2 plus LC, CdCl2 plus SeCl4 and LC groups. Hepatic aminotransferase (aspartate aminotransferase [AST] and alanine transaminase [ALT]) activity and tumor necrosis factor-alpha [TNF-α] levels, as well as the antioxidant biomarkers (superoxide dismutase [SOD], glutathione reductase [GRx], glutathione-S-transferase [GST] and catalase [CAT], were examined. Histological and transmission electron microscopic [TEM] variations in the liver were used as indicators of liver damage after the administration of CdCl2-alone or CdCl2 with LC, SeCl4, or both. Genotoxic effects of CdCl2 were also evaluated and the possible roles of SeCl4 and/or LC on the expression of the antioxidant enzymes were studied. Results showed that administration of LC and SeCl4 decreased CdCl2-induced increase in ALT and AST levels and reduced oxidative stress to normal levels. In addition, LC combined with SeCl4 had a highly synergistic effect and elevated significantly the enzymatic antioxidants and decreased lipid peroxidation levels compared with those in the CdCl2-treated group. It is clear from the data that both LC and SeCl4 inhibit liver injury and improve the redox state in mice.

Keywords: Cadmium; Hepatotoxicity; Histopathology; L-Carnitine; Redox status; Selenium; Transmission electron microscope.

MeSH terms

  • Alanine Transaminase / metabolism
  • Animals
  • Anticarcinogenic Agents / pharmacology
  • Anticarcinogenic Agents / therapeutic use*
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use*
  • Apoptosis / drug effects
  • Aspartate Aminotransferases / metabolism
  • Cadmium Chloride / toxicity*
  • Carnitine / pharmacology
  • Carnitine / therapeutic use*
  • Catalase / metabolism
  • Chemical and Drug Induced Liver Injury / drug therapy*
  • Chemical and Drug Induced Liver Injury / metabolism
  • Glutathione Reductase / metabolism
  • Glutathione Transferase / metabolism
  • Lipid Peroxidation / drug effects
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Mice
  • Oxidative Stress / drug effects
  • Selenium / pharmacology
  • Selenium / therapeutic use*
  • Superoxide Dismutase / metabolism

Substances

  • Anticarcinogenic Agents
  • Antioxidants
  • Catalase
  • Superoxide Dismutase
  • Glutathione Reductase
  • Glutathione Transferase
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Selenium
  • Cadmium Chloride
  • Carnitine