Histone deacetylase inhibitor, sodium butyrate, attenuates gentamicin-induced nephrotoxicity by increasing prohibitin protein expression in rats

Eur J Pharmacol. 2013 May 5;707(1-3):147-54. doi: 10.1016/j.ejphar.2013.03.018. Epub 2013 Mar 22.

Abstract

The major purpose in our study was to investigate the effects of sodium butyrate (NaBu) on nephrotoxicity induced by gentamicin in rats and determine further whether the protective effect is mediated by modulation of prohibitin protein expression. Gentamicin was injected intraperitoneally (100 mg/kg body weight) once daily for 8 days to induce nephrotoxicity. The effect of acute and chronic treatment of sodium butyrate on nephrotoxicity induced by gentamicin was assessed. Various doses of sodium butyrate (50, 100, 200 mg/kg, i.p.) was administered 30 min prior to the daily gentamicin injection. Histological analysis was used to evaluate the lesions in kidney after gentamicin administration. Expression of prohibitin was evaluated with immunohistochemical and western blot analysis. The present study demonstrated that gentamicin treatment for 8 consecutive days significantly increased in the levels of blood urea nitrogen, creatinine, kidney injury molecule (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) which indicated nephrotoxicity induced by gentamicin. In addition, chronic treatment with NaBu significantly attenuated gentamicin-induced nephrotoxicity by increasing activities of superoxide dismutase, catalase and reduced glutathione. Immunohistochemical studies in gentamicin-induced rats also demonstrated an increase in the levels of inducible prohibitin after treatment with sodium butyrate. Our results indicated that sodium butyrate, a histone deacetylase inhibitor, decreased gentamicin-induced nephrotoxicity by enhancing renal antioxidant enzymes activity and the expression of prohibitin protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / toxicity
  • Antioxidants / metabolism
  • Blotting, Western
  • Butyrates / administration & dosage
  • Butyrates / pharmacology*
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation / drug effects
  • Gentamicins / toxicity*
  • Histone Deacetylase Inhibitors / administration & dosage
  • Histone Deacetylase Inhibitors / pharmacology*
  • Injections, Intraperitoneal
  • Kidney Diseases / chemically induced
  • Kidney Diseases / physiopathology
  • Kidney Diseases / prevention & control*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Repressor Proteins / genetics

Substances

  • Anti-Bacterial Agents
  • Antioxidants
  • Butyrates
  • Gentamicins
  • Histone Deacetylase Inhibitors
  • Repressor Proteins
  • prohibitin