Telfairia occidentalis (Cucurbitaceae) pulp extract mitigates rifampicin-isoniazid-induced hepatotoxicity in an in vivo rat model of oxidative stress

J Integr Med. 2019 Jan;17(1):46-56. doi: 10.1016/j.joim.2018.11.008. Epub 2018 Dec 1.

Abstract

Objective: Drug-induced liver injury complicates antituberculosis drug treatment and is a leading cause of death worldwide. The aim of this study is to establish the ethnomedicinal claim of hepatoprotective effects of fruit pulp extract of Telfairia occidentalis against rifampicin (RIF) and isoniazid (INH)-induced oxidative stress in rats.

Methods: T. occidentalis pulp extract (TOPE) (125-500 mg/kg) and silymarin (50 mg/kg) were evaluated in an induced hepatotoxicity model of oxidative stress in Wistar rats by intoxication with RIF and INH (100 mg/kg each) orally for 60 d. Markers indicating oxidative stress and hepatic damage such as alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were assessed. Biomarkers of antioxidant status, including catalase, glutathione reductase, glutathione peroxidase and superoxide dismutase, and marker of lipid peroxidation, malondialdehyde (MDA), were assayed using standard procedures. The hematological profile, lipid profile, serum markers for kidney function and histopathological examination were also assessed.

Results: Intoxication with RIF and INH markedly reduced the hematological indices and elevated the biochemical enzyme markers (AST, ALT and ALP, P < 0.001) and lipid profile (P < 0.001), while antioxidant biomarkers were significantly (P < 0.01) depressed and MDA was elevated. However, pretreatment with TOPE significantly (P < 0.001) alleviated this alteration and sustained the antioxidant potentials. The histopathological morphology supports the biochemical evidence of hepatoprotection.

Conclusion: Current study is indicative of potential antioxidant activity, hepatoprotective effects and plausible therapeutic alleviation of RIF-INH-induced hepatotoxicity of TOPE in laboratory animals.

Keywords: Antioxidant; Hepatoprotective; Lipid peroxidation; Oxidative stress; Pulp extract; Telfairia occidentalis.

MeSH terms

  • Alanine Transaminase / genetics
  • Alanine Transaminase / metabolism
  • Animals
  • Aspartate Aminotransferases / genetics
  • Aspartate Aminotransferases / metabolism
  • Catalase / genetics
  • Catalase / metabolism
  • Chemical and Drug Induced Liver Injury / drug therapy*
  • Chemical and Drug Induced Liver Injury / genetics
  • Chemical and Drug Induced Liver Injury / metabolism
  • Cucurbitaceae / chemistry*
  • Humans
  • Isoniazid / adverse effects*
  • Male
  • Malondialdehyde / metabolism
  • Oxidative Stress / drug effects
  • Plant Extracts / administration & dosage*
  • Rats
  • Rats, Wistar
  • Rifampin / adverse effects*
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism

Substances

  • Plant Extracts
  • Malondialdehyde
  • Catalase
  • Superoxide Dismutase
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Isoniazid
  • Rifampin