Caffeic acid phenethyl ester (CAPE) protects mitochondrial complex I activity from renal ischemia induced injury

Abstract

Introduction: The duration of hypoxia induced by renal ischemia is very important factor in the development of renal failure. Our previous studies showed, that ischemia causes mitochondrial damage and diminishes the activity of mitochondrial Complex I. Therefore, the protective compounds that could improve mitochondrial function during ischemia are of great importance. Therefore, the aim of this study was to investigate the possible protective effects of caffeic acid phenethyl ester (CAPE) Methods: Animals were pre-treated with CAPE (22 mg/kg, intraperitoneally) 1.5 h prior induction of ischemia. Then rat kidneys were exposed for 20 min of total (in vitro) ischemia (at 37 ºC) and mitochondria were isolated. The mitochondrial respiration rates were measured at 37 ºC using Clark-type electrode with glutamate/malate or succinate as respiratory substrates. Complex I activity was determined spectrophotometrically by following the kinetics of NADH oxidation at 340 nm Results: We revealed, that ischemia caused the inhibition of suppression of the ADPstimulated renal mitochondrial respiration rate and the respiratory control index (RCI) as compared to control with both, complex I dependent substrate glutamate/malate (52 % and 58%, p<0.05) and Complex II dependent substrate succinate (44 % and 41%, p<0.05). In accordance with this, Complex I activity decreased by 23 %, p<0.05 after ischemia. Pretreatment of rats with CAPE improved by 20% and 33% the ischemia -induced decrease in ADP-dependent respiration rate with glutamate/malate and RCI. The activity of Complex I was recovered almost by 33% (p<0.05) as compared to untreated group. However, there was no protective effect of CAPE on succinate (Complex II) oxidation. Conclusion: 20 min of warm ischemia in vitro leads to decrease in mitochondrial oxidative phosphorylation and Complex I activity in rat kidney. Caffeic acid phenethyl ester (CAPE) protects mitochondrial complex I activity from renal ischemia induced inj