Alpha lipoic acid prevents doxorubicin-induced nephrotoxicity by mitigation of oxidative stress, inflammation, and apoptosis in rats

J Biochem Mol Toxicol. 2017 Sep;31(9). doi: 10.1002/jbt.21940. Epub 2017 Jun 9.

Abstract

This study aimed to evaluate the protective effects of alpha lipoic acid (ALA) against doxorubicin (DOX)-induced nephrotoxicity in rats. A single dose of DOX (7.5 mg/kg i.v.) induced nephrotoxicity evidenced by significant elevations in kidney weight, kidney/body weight ratio, serum urea, creatinine, tumor necrosis factor alpha, and renal contents of malondialdehyde, nitric oxide, cyclooxygenase-2, and caspase-3. Also, it causes significant reduction in final body weight, serum albumin, renal contents of reduced glutathione and superoxide dismutase activity. Histopathological changes in the kidney tissue confirmed the nephrotoxic effect. In contrast, pretreatment with ALA (50 mg/kg, orally) for 14 days before DOX and for 7 days after DOX administration mitigated renal toxicity evidenced by greater improvement in the examined oxidative stress, inflammation, and apoptosis parameters. In conclusion, ALA had promising protective effects against DOX-induced nephrotoxicity that might be attributed to its antioxidant, anti-inflammatory, and antiapoptoic activities.

Keywords: Alpha lipoic acid; apoptosis; doxorubicin; inflammation; nephrotoxicity; oxidative stress.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Doxorubicin / adverse effects*
  • Doxorubicin / pharmacology
  • Inflammation / chemically induced
  • Inflammation / metabolism
  • Inflammation / pathology
  • Inflammation / prevention & control
  • Kidney / metabolism*
  • Kidney / pathology
  • Kidney Diseases* / chemically induced
  • Kidney Diseases* / metabolism
  • Kidney Diseases* / pathology
  • Kidney Diseases* / prevention & control
  • Male
  • Oxidative Stress / drug effects*
  • Rats
  • Thioctic Acid / pharmacology*

Substances

  • Thioctic Acid
  • Doxorubicin