Martinefski Manuela R, Contin Mario D, Rodriguez Myrian R, Geréz Estefanía M, Galleano Mónica L, Lucangioli Silvia E, Bianciotti Liliana G, Tripodi Valeria P
Analytical Chemistry, School of Pharmacy and Biochemistry, Universidad de Buenos Aires, Buenos Aires, Argentina.
Liver Int. 2014 Aug;34(7):1040-8. doi: 10.1111/liv.12323. Epub 2013 Oct 2.
BACKGROUND & AIMS: Intrahepatic cholestasis of pregnancy is a high-risk liver disease given the eventual deleterious consequences that may occur in the foetus. It is accepted that the abnormal accumulation of hydrophobic bile acids in maternal serum are responsible for the disease development. Hydrophobic bile acids induce oxidative stress and apoptosis leading to the damage of the hepatic parenchyma and eventually extrahepatic tissues. As coenzyme Q (CoQ) is considered an early marker of oxidative stress in this study, we sought to assess CoQ levels, bile acid profile and oxidative stress status in intrahepatic cholestasis.
CoQ, vitamin E and malondialdehyde were measured in plasma and/or tissues by HPLC-UV method whereas serum bile acids by capillary electrophoresis in rats with ethinyl estradiol-induced cholestasis and women with pregnancy cholestasis.
CoQ and vitamin E plasma levels were diminished in both rats and women with intrahepatic cholestasis. Furthermore, reduced CoQ was also found in muscle and brain of cholestatic rats but no changes were observed in heart or liver. In addition, a positive correlation between CoQ and ursodeoxycholic/lithocholic acid ratio was found in intrahepatic cholestasis suggesting that increased plasma lithocholic acid may be intimately related to CoQ depletion in blood and tissues.
Significant CoQ and vitamin E depletion occur in both animals and humans with intrahepatic cholestasis likely as the result of increased hydrophobic bile acids known to produce significant oxidative stress. Present findings further suggest that antioxidant supplementation complementary to traditional treatment may improve cholestasis outcome.
鉴于妊娠肝内胆汁淤积症可能对胎儿产生最终有害后果，它是一种高危肝脏疾病。公认的是，母体血清中疏水性胆汁酸的异常蓄积是该疾病发展的原因。疏水性胆汁酸会诱导氧化应激和细胞凋亡，导致肝实质损伤，并最终累及肝外组织。由于辅酶Q（CoQ）在本研究中被视为氧化应激的早期标志物，我们试图评估妊娠肝内胆汁淤积症患者的辅酶Q水平、胆汁酸谱和氧化应激状态。
采用高效液相色谱-紫外检测法（HPLC-UV）测定大鼠和妊娠肝内胆汁淤积症患者血浆和/或组织中的辅酶Q、维生素E和丙二醛水平，而血清胆汁酸则通过毛细管电泳法测定，其中大鼠由乙炔雌二醇诱导胆汁淤积，患者为妊娠肝内胆汁淤积症。
肝内胆汁淤积症大鼠和患者的血浆辅酶Q和维生素E水平均降低。此外，胆汁淤积症大鼠的肌肉和脑中辅酶Q也减少，但心脏或肝脏未观察到变化。此外，肝内胆汁淤积症患者中辅酶Q与熊去氧胆酸/石胆酸比值呈正相关，提示血浆石胆酸升高可能与血液和组织中辅酶Q耗竭密切相关。
肝内胆汁淤积症的动物和人类均出现显著的辅酶Q和维生素E耗竭，这可能是已知会产生显著氧化应激的疏水性胆汁酸增加所致。目前的研究结果进一步表明，在传统治疗的基础上补充抗氧化剂可能会改善胆汁淤积症的预后。
