(‒)-Epicatechin modulates systemic and renal modifications in a rat model of endotoxemia

Abstract

Endotoxemia, characterized by systemic inflammation, is a major causeof acute kidney injury. In this work, Sprague-Dawley male rats, pretreatedfor 4 days with control diet or with diets supplemented with 20(low-level, LLE) or 80 (high-level, HLE) mg ()-epicatechin (EC)/kg ofbody weight/day, were challenged with bacterial lipopolysaccharide(LPS) (i.p. 4 mg/kg BW) and sacrificed 6 h post LPS administration. InLPS-treated endotoxemic animals, plasma GPT, GOT and LDH levels wereslightly or non-affected; nitric oxide (NO) levels in blood, measured byEPR, increased significantly, and HLE avoided 41% (p<0.05) of thatincrease. Plasma TNF-alpha levels correlated with NO changes (r¼0.52,p¼0.02). Endotoxemic animals showed increased urea levels, partiallyprevented by HLE. In kidneys, NO and TNF-alpha levels correlated withthe systemic changes. The role of autophagy in endotoxemia is suggestedas a renoprotective response. LPS treatment led to LC3II accumulation inkidney of endotoxemic animals (87% over controls, p<0.05) and HLEcompletely avoid that increase. Integration of this marker of autophagywith results on apoptosis allows underlie the relevance of programed celldeath under inflammation and the protection exerted by EC. Supportedby UBACyT 20020160100132 (CGF) and 20020170100586BA (MG) andPIP 11220170100585CO (MG).