Hydroxycinnamic acids derivatives effect on rat kidney mitochondria after ischemia

Abstract

Ischemia/reperfusion injury is a major cause of acute kidney injury (AKI). Latest data shows, that AKI is recognized as a common complication of the coronavirus disease, and is often evident at hospital admission. Derivatives of caffeic acid, a subtype of hydroxycinnamic acid, are widely distributed in the plants, fruits and vegetables and have broad bioactivities. They typically occur not as free acids, but as esters, amides, and glycosides, or as dimers and other more complex forms. The aim of this study was to evaluate caffeic acid phenethyl ester (CAPE) and 3,5-dicaffeoylquinic acid (22 mg/kg of rat body) effect on kidney mitohondria functions after kidney ischemia/reperfusion in vivo. We injected CAPE and 3,5-dicaffeoylquinic acid into rat tail vein 90 minutes before inducing 40-minute kidney ischemia followed by 30-minute reperfusion and measured mitochondrial functions using high resolution respirometry system Oxygraph-2k. Our results showed that, ischemia/reperfusion alone caused significant injury of the mitochondrial function. Pretreatment of rats with CAPE alleviated the ischemia-induced damage of the mitochondria. Routine respiration rate after 40 min of ischemia/30 min of reperfusion after pretreatment with CAPE was practically restored to the control level. The mitochondrial state 3 respiration with glutamate/malate increased by 2.3-fold in CAPE group. Pretreatment of rats with 3,5-dicaffeoylquinic acid did not protected the ischemia-induced damage of the mitochondria. In conclusion, CAPE protects the kidney mitochondria from ischemia/reperpfusion induced damage in an in vivo model, whereas 3,5-dicaffeoylquinic acid did not show positive effect. CAPE shows potential as a therapeutic agent for the development of pharmaceutical preparations.