Reno-protective effects of epigallocatechingallate in a small piglet model of extracorporeal circulation

Pharmacol Res. 2013 Jan;67(1):68-78. doi: 10.1016/j.phrs.2012.10.011. Epub 2012 Oct 24.

Abstract

Cardiopulmonary bypass still often is a necessary tool in cardiac surgery in particular in the correction of congenital heart defects in small infants. Nevertheless, among the complications linked to extracorporeal circulation (ECC) with cardiopulmonary bypass (CPB) in both infants and adults one of the most serious problems is renal impairment. Since this might be caused by ischemia/reperfusion injury and accumulation of free radicals, we used (-)-epigallocatechin-3-gallate (EGCG), a derivate from green tea, which is known to possess antioxidant, antiapoptotic and NO-scavenging properties in order to find out whether EGCG may protect the kidney. 23 four-week-old Angler Sattelschwein-piglets (8-15 kg) were divided into three groups: control-group (n=7), ECC-group (n=10), EGCG-group (n=6). The ECC- and EGCG-group were thoracotomized and underwent CPB for 120 min followed by a 90-min recovery-time. The EGCG-group received 10 mg/kg EGCG before and after CPB. Histology revealed that CPB led to widening of Bowman's capsule, and to vacuolization of proximal tubular cells (p<0.05) which could be prevented by EGCG (p<0.05). Using immunohistology, we found significant nuclear translocation of hypoxia-inducible-factor-1-alpha (HIF-1-alpha) and increased nitrotyrosine formation in the ECC-group. Both were significantly (p<0.05) inhibited by EGCG. ECC-induced loss of energy-rich phosphates was prevented by EGCG. In blood samples we found that CPB resulted in increases in creatinine and urea (in serum) and led to loss of total protein (p<0.05), which all was not present in EGCG-treated animals. We conclude that CPB causes damage in the kidney which can be attenuated by EGCG.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis Inducing Factor / metabolism
  • Blood Pressure
  • Cardiopulmonary Bypass*
  • Catechin / analogs & derivatives*
  • Catechin / pharmacology
  • Creatinine / blood
  • Heart Rate
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney / physiopathology
  • Poly Adenosine Diphosphate Ribose / metabolism
  • Protective Agents / pharmacology*
  • Swine
  • Tyrosine / analogs & derivatives
  • Tyrosine / metabolism
  • Urea / blood

Substances

  • Apoptosis Inducing Factor
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Protective Agents
  • Poly Adenosine Diphosphate Ribose
  • 3-nitrotyrosine
  • Tyrosine
  • Catechin
  • Urea
  • Creatinine
  • epigallocatechin gallate