Thymoquinone improves the kidney and liver changes induced by chronic cyclosporine A treatment and acute renal ischaemia/reperfusion in rats

J Pharm Pharmacol. 2015 May;67(5):731-9. doi: 10.1111/jphp.12363. Epub 2015 Feb 3.

Abstract

Objectives: This study was designed to evaluate the effects of chronic cyclosporine A (CsA) treatment and acute renal ischaemia/reperfusion (I/R) on the kidney and liver in thymoquinone (TQ)-treated rats.

Methods: In the CsA study, adult male rats were divided into control, CsA (25 mg/kg per day), TQ (10 mg/kg per day) and CsA + TQ groups, and rat treatment was for 28 days. In the I/R study, adult male rats were divided into sham-operated, I/R (renal ischaemia for 60 min followed by 60 min reperfusion) and TQ + I/R (TQ 10 mg/kg, 24 h and 1 h before ischaemia) groups.

Key findings: CsA treatment and renal I/R caused kidney and liver dysfunction as evaluated by histopathological changes and biochemical parameters. TQ treatment reduced elevated serum indices back to control levels and ameliorated CsA-induced kidney and liver histopathological changes. In renal and hepatic tissues, CsA and renal I/R induced significant increases in malondialdehyde levels with significant decreases in reduced glutathione levels and superoxide dismutase activities. Such changes in oxidative stress markers were counteracted by TQ treatment.

Conclusions: Kidney and liver injury due to CsA or renal I/R can be significantly reduced by TQ, which resets the oxidant/antioxidant balance of the affected organs through scavenging free radicals and antilipoperoxidative effects.

Keywords: cyclosporine A; hepatotoxicity; nephrotoxicity; renal ischaemia/reperfusion; thymoquinone.

MeSH terms

  • Alanine Transaminase / blood
  • Alkaline Phosphatase / blood
  • Animals
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use
  • Benzoquinones / pharmacology*
  • Benzoquinones / therapeutic use*
  • Creatinine / blood
  • Cyclosporine / adverse effects*
  • Glutathione / metabolism
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney / pathology
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Malondialdehyde
  • Oxidative Stress / drug effects*
  • Rats
  • Reperfusion Injury / blood
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / pathology
  • Superoxide Dismutase / metabolism
  • Urea / blood

Substances

  • Antioxidants
  • Benzoquinones
  • Malondialdehyde
  • Cyclosporine
  • Urea
  • Creatinine
  • Superoxide Dismutase
  • Alanine Transaminase
  • Alkaline Phosphatase
  • Glutathione
  • thymoquinone