Promising therapeutic effect of coenzyme Q10 in ethinyl estradiol-induced cholestasis.

MARTINEFSKI, MANUELA; SILVIA LUCANGIOLI; FABIAN BUONTEMPO; MYRIAN R. RODRIGUEZ; VALERIA TRIPODI

Mar del Plata

Congreso; LXI REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC) LXIV REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA (SAI) XLVIII REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE FARMACOLOGÍA EXPERIMENTAL (SAFE) VII REUNIÓN ANUAL DE LA SOCIEDAD; 2016

SAIC

􀀫ntrahepatic cholestasis of pregnancy 􀀊􀀫C􀀲􀀋 is a high ris􀁍 liverdisease given the eventual deleterious consequences that mayoccur in the fetous. 􀀫C􀀲 is characterized by the accumulation ofbile acids, particularly hydrophobic bile acids such as litocholic acid􀀊LCA􀀋, 􀁙hich induces oxidative stress and apoptosis. 􀀹e previouslyreported that 􀁙omen 􀁙ith 􀀫􀀲C sho􀁙 decreased coenzyme􀀳􀀓􀀒 􀀊Co􀀳􀀓􀀒􀀋 and enhanced bile acids in plasma. These findings􀁙ere also observed in ethinyl estradiol 􀀊EE􀀋􀀏induced cholestasisin rats. The aim of this 􀁙or􀁍 􀁙as to evaluate the effect of Co􀀳􀀓􀀒supplementation in EE-induced cholestasis in rats. Cholestasis􀁙as induced in Sprague􀀏􀀦a􀁙ley rats by a daily intraperitonealinjection of 􀀗 mg/􀁍g EE for 􀀗 days 􀀊EE􀀋. A group of these ratsalso received daily oral 􀀔􀀗􀀒 mg/􀁍g Co􀀳􀀓􀀒 supplementation for 􀀗days 􀀊EE􀀍Co􀀳􀀓􀀒􀀋. Another group of rats received only Co􀀳􀀓􀀒supplementation for the same period of time 􀀊Co􀀳􀀓􀀒􀀋. Serum,bile acids 􀀊total and LCA􀀋, coenzyme 􀀳􀀛 􀀊Co􀀳􀀛􀀋 and Co􀀳􀀓􀀒, aspartateaminotransferase, alanine aminotransferase, and al􀁍alinephosphatase 􀁙ere assessed. 􀀤ile flo􀁙 􀁙as also measured. 􀀰odifferences 􀁙ere observed bet􀁙een Co􀀳􀀓􀀒 and control groupsexcept for an increase in plasma Co􀀳􀀓􀀒 􀀊p􀀞􀀒.􀀒􀀒􀀓􀀋. Ho􀁙ever,Co􀀳􀀓􀀒 supplementation in cholestatic rats 􀀊EE􀀍Co􀀳􀀓􀀒􀀋 increasedboth Co􀀳􀀓􀀒 and Co􀀳􀀛 plasma levels 􀀊p􀀞􀀒.􀀒􀀗􀀋, and enhanced bileflo􀁙􀀊p􀀞􀀒.􀀒􀀗􀀋 as compared 􀁙ith EE. Furthermore, it also decreasedserum al􀁍aline phosphatase and bile acids, particularly LCA levelsas compared 􀁙ith EE 􀀊p􀀞􀀒.􀀒􀀗􀀋. 􀀲resent findings sho􀁙 that Co􀀳􀀓􀀒administration improved cholestasis and further suggest thatCo􀀳􀀓􀀒 supplementation may be a potential therapeutic strategyin estrogen-induced cholestasis in humans as ICP.