Thymoquinone and curcumin prevent gentamicin-induced liver injury by attenuating oxidative stress, inflammation and apoptosis

J Physiol Pharmacol. 2014 Dec;65(6):823-32.


This study was conducted to assess the preventive effect of two plant constituents, thymoquinone and curcumin, on gentamicin-induced deleterious effect on liver function, integrity and histological architecture. The gentamicin was intraperitoneally injected to rats at dose level of 100 mg/kg b.w. (every other day) for 21 days. The thymoquinone and curcumin were concurrently and orally administered at dose level of 20 mg/kg b.w. (every other day) to gentamicin-injected rats. The present data indicated that thymoquinone and curcumin significantly prevented the gentamicin-induced elevations of serum AST, ALT and LDH activities as well as tumor necrosis factor alpha (TNF-α) and total bilirubin levels. On the other hand, both agents markedly ameliorated the gentamicin-induced decrease in serum total protein, albumin and albumin/globulin ratio. In addition, the gentamicin-induced liver histological alterations including hydropic degeneration of hepatocytes, fatty changes, inflammatory cell infiltration and congestion of portal vein were successfully amended by thymoquinone and curcumin. The elevated proapoptotic proteins caspase 3 and Bax expression in cytoplasm and nucleus of hepatocytes of gentamicin-injected rats were reduced to normal value as a result of thymoquinone and curcumin administration while the lowered expression of antiapoptotic protein Bcl-2 was increased. Based on the previous findings, it can be concluded that thymoquinone and curcumin successfully prevents the deleterious effects on liver function and histological integrity to more or less the same degree by enhancing anti-oxidant defense system, suppression of oxidative stress and attenuation of inflammation and apoptosis.

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use*
  • Apoptosis / drug effects
  • Aspartate Aminotransferases / blood
  • Benzoquinones / pharmacology
  • Benzoquinones / therapeutic use*
  • Caspase 3 / metabolism
  • Chemical and Drug Induced Liver Injury / blood
  • Chemical and Drug Induced Liver Injury / drug therapy*
  • Chemical and Drug Induced Liver Injury / metabolism
  • Chemical and Drug Induced Liver Injury / pathology
  • Curcumin / pharmacology
  • Curcumin / therapeutic use*
  • Gentamicins
  • Glutathione / metabolism
  • Glutathione Peroxidase / metabolism
  • L-Lactate Dehydrogenase / blood
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Oxidative Stress / drug effects
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Rats
  • Superoxide Dismutase / metabolism
  • Tumor Necrosis Factor-alpha / blood
  • bcl-2-Associated X Protein / metabolism


  • Anti-Inflammatory Agents
  • Antioxidants
  • Bax protein, rat
  • Benzoquinones
  • Gentamicins
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Necrosis Factor-alpha
  • bcl-2-Associated X Protein
  • L-Lactate Dehydrogenase
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Caspase 3
  • Glutathione
  • Curcumin
  • thymoquinone