Protective effects of taurine on doxorubicin-induced acute hepatotoxicity through suppression of oxidative stress and apoptotic responses

Anticancer Drugs. 2016 Jan;27(1):17-23. doi: 10.1097/CAD.0000000000000299.

Abstract

The organ toxicity of doxorubicin (DOX), an anthracycline antineoplastic agent, narrows the therapeutic window despite its clinical usefulness. In the present study, we determined whether taurine protected against DOX-induced hepatic injury, and explored the molecular mechanisms underlying the suppressive effects of taurine in terms of alterations in oxidative stress and apoptotic responses. DOX-induced body weight loss was completely suppressed by taurine treatment. Elevations in the serum activity levels of lactate dehydrogenase, aspartate aminotransferase, and alanine aminotransferase by DOX were also dose-dependently attenuated by a concurrent treatment with taurine. Superoxide dismutase activity and reduced glutathione content in the liver were decreased following the administration of DOX, whereas these changes were suppressed when 10 mg/kg taurine was given in combination with DOX. Taurine attenuated the increased expression of mRNAs for Fas and Bax after DOX exposure. Furthermore, the formation of cleaved caspase-3 protein in the group given DOX with taurine was lower than that in the group treated with DOX alone. Our results suggest that taurine can protect against DOX-induced acute hepatic damage, the underlying mechanism of which is attributable to the suppression of oxidative stress and apoptotic responses.

MeSH terms

  • Alanine Transaminase / metabolism
  • Animals
  • Antibiotics, Antineoplastic / toxicity*
  • Apoptosis / drug effects*
  • Aspartate Aminotransferases / metabolism
  • Chemical and Drug Induced Liver Injury / metabolism
  • Chemical and Drug Induced Liver Injury / pathology
  • Chemical and Drug Induced Liver Injury / prevention & control*
  • Doxorubicin / toxicity*
  • Glutathione / metabolism
  • L-Lactate Dehydrogenase / metabolism
  • Male
  • Mice
  • Oxidative Stress / drug effects*
  • Superoxide Dismutase / metabolism
  • Taurine / therapeutic use*

Substances

  • Antibiotics, Antineoplastic
  • Taurine
  • Doxorubicin
  • L-Lactate Dehydrogenase
  • Superoxide Dismutase
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Glutathione