Renoprotective effect of berberine via intonation on apoptosis and mitochondrial-dependent pathway in renal ischemia reperfusion-induced mutilation

Ren Fail. 2015 Apr;37(3):482-93. doi: 10.3109/0886022X.2014.996843. Epub 2015 Jan 19.

Abstract

Ischemic acute renal failure is a condition that extends subsequent to sudden and momentary fall in overall or regional blood flow to the kidney. The present investigation was deliberated to scrutinize the renoprotective potential of berberine in animal model of renal ischemia reperfusion (RIR) induced dent via assessment of various biochemical and molecular biomarkers. Male Wistar rats were anesthetized and the right kidney was removed through a small flank incision. Renal ischemia reperfusion was persuaded in uni-nephrectomized rats by occlusion of left renal artery for 45 min and reperfusion for 4 weeks. After 4 weeks of treatment of berberine (10, 20, and 40 mg/kg, p.o.), hemodynamic and left ventricular function were evaluated. Induction of ischemia reperfusion resulted callous mutilation in kidney which was confirmed by alterations in oxidative stress (SOD, GSH, and MDA), membrane bound enzymes, kidney function markers (serum creatinine and BUN), and mitochondrial dysfunction. Moreover, RIR injury exhibited incredible alterations in mRNA expression of KIM-1, NGAL, Caspase-3, Bax, Bcl-2, and TNF-α levels. Conversely treatment of berberine (20 and 40 mg/kg) significantly (p < 0.01 and p < 0.001) restored ischemia reperfusion induced marring via intonation of biochemical and molecular biomarkers. To sum up, berberine demonstrated compelling renoprotective effect in RIR injury via caspase-mitochondria-dependent pathway.

Keywords: Bax; Bcl-2; KIM-1; NGAL; TNF-α; berberine; caspase-3; cytochrome oxidase; renal ischemia reperfusion.

MeSH terms

  • Acute Kidney Injury* / complications
  • Acute Kidney Injury* / physiopathology
  • Animals
  • Apoptosis / drug effects
  • Berberine / pharmacology*
  • Biomarkers / metabolism
  • Caspase 3 / metabolism
  • Creatinine / blood
  • Disease Models, Animal
  • Ischemia / physiopathology*
  • Kidney Function Tests / methods
  • Kidney* / blood supply
  • Kidney* / physiopathology
  • Male
  • Mitochondria* / drug effects
  • Mitochondria* / metabolism
  • Oxidative Stress / drug effects
  • Protective Agents / pharmacology
  • Rats
  • Rats, Wistar
  • Reperfusion Injury* / etiology
  • Reperfusion Injury* / metabolism
  • Reperfusion Injury* / physiopathology
  • Reperfusion Injury* / prevention & control
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Biomarkers
  • Protective Agents
  • TNF protein, human
  • Tumor Necrosis Factor-alpha
  • Berberine
  • Creatinine
  • Caspase 3