Rutin ameliorates mercuric chloride-induced hepatotoxicity in rats via interfering with oxidative stress, inflammation and apoptosis

J Trace Elem Med Biol. 2019 Dec:56:60-68. doi: 10.1016/j.jtemb.2019.07.011. Epub 2019 Aug 1.

Abstract

Objective: Mercury is a global environmental pollutant and is responsible for several organ pathophysiology including oxidative stress-induced liver disorders. Therefore, the present study was conducted to evaluate the potential ameliorative effects of rutin on mercury chloride (HgCl2)-induced hepatotoxicity in adult male rats.

Methods: HgCl2 was intraperitoneally injected at a dose of 1.23 mg/kg body weight for 7 days alone or in combination with the orally rutin (50 and 100 mg/kg body weight).

Results: Rutin treatment significantly improved liver function tests [alkaline phosphatase (ALP), aspartate aminotransferase (AST) and alanine aminotransferase (ALT)], and increased activities of antioxidant defense system [catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx)] and glutathione (GSH) content. The histological alterations and epidermal growth factor receptor (EGFR) expression in the HgCl2-induced liver tissues were decreased by administration of rutin. Furthermore, rutin reversed the changes in levels of apoptosis and inflammation related proteins involving p53, Bcl-2 associated X protein (Bax), B-cell lymphoma-2 (Bcl-2), cytochrome c, nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNF-α), B-cell lymphoma-3(Bcl-3) and interleukin-1β (IL-1β), and inhibited p38α mitogen-activated protein kinase (MAPK) and cysteine aspartate specific protease-3 (caspase-3) activations.

Conclusion: The data of the present study suggest that rutin effectively suppress HgCl2-induced hepatotoxicity by ameliorating oxidative stress, inflammation and apoptosis.

Keywords: Apoptosis; Epidermal growth factor receptor; Hepatotoxicity; Inflammation; Mercuric chloride; Rutin.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Antioxidants / metabolism
  • Apoptosis / drug effects*
  • Biomarkers / blood
  • ErbB Receptors / metabolism
  • Glutathione / metabolism
  • Inflammation / pathology*
  • Lipid Peroxidation / drug effects
  • Liver / drug effects
  • Liver / enzymology
  • Liver / injuries
  • Liver / pathology*
  • Male
  • Mercuric Chloride / toxicity*
  • Oxidative Stress / drug effects*
  • Rats, Sprague-Dawley
  • Rutin / chemistry
  • Rutin / pharmacology
  • Rutin / therapeutic use*
  • Tumor Suppressor Protein p53 / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Biomarkers
  • Tumor Suppressor Protein p53
  • Mercuric Chloride
  • Rutin
  • ErbB Receptors
  • p38 Mitogen-Activated Protein Kinases
  • Glutathione