In adults,the hepatobiliary system,together with the kidney,constitute the main routes for the elimination of several endogenous and xenobiotic compounds into bile and urine,respectively.However,during intrauterine li...In adults,the hepatobiliary system,together with the kidney,constitute the main routes for the elimination of several endogenous and xenobiotic compounds into bile and urine,respectively.However,during intrauterine life the biliary route of excretion for cholephilic compounds,such as bile acids and biliary pigments,is very poor.Although very early in pregnancy the fetal liver produces bile acids,bilirubin and biliverdin,these compounds cannot be efficiently eliminated by the fetal hepatobiliary system,owing to the immaturity of the excretory machinery in the fetal liver.Therefore,the potentially harmful accumulation of cholephilic compounds in the fetus is prevented by their elimination across the placenta.Owing to the presence of detoxifying enzymes and specifi c transport systems at different locations of the placental barrier,such as the endothe-lial cells of chorionic vessels and trophoblast cells,this organ plays an important role in the hepatobiliary-like function during intrauterine life.The relevance of this excretory function in normal fetal physiology is evident in situations where high concentrations of biliary compounds are accumulated in the mother.This may result in oxidative stress and apoptosis,mainly in the placenta and fetal liver,which might affect normal fetal development and challenge the fate of the pregnancy.The present article reviews current knowledge of the mechanisms underlying the hepatobiliary function of the fetal-placental unit and the repercussions of several pathological conditions on this tandem.展开更多
Chronic renal failure(CRF)is a type of progressive chronic kidney disease with the alteration of substrates excretion.However,changes in renal excretion pathways remain unclear in CRF.This study aimed to evaluate the ...Chronic renal failure(CRF)is a type of progressive chronic kidney disease with the alteration of substrates excretion.However,changes in renal excretion pathways remain unclear in CRF.This study aimed to evaluate the changes in renal excretion pathways of exogenous and endogenous substrates in CRF rats.Results showed that the levels of cystatin C,creatinine,and urea nitrogen were dramatically increased in the adenine(50 or 100 mg/kg)-induced CRF rats.The levels of rOCT2 were dose-dependently up-regulated by adenine,and rMRP2 and rMATE1 levels were dose-dependently down-regulated,while rMRP4 was induced by adenine(50).Plasma concentrations of metformin,p-aminohippurate,and furosemide in the adenine(100)group were significantly increased compared with the control group.However,plasma concentrations of metformin and p-aminohippurate were slightly changed in the adenine(50)group.Consistently,urinary excretions of metformin and p-aminohippurate were unaffected.In addition,renal N1-methylnicotinamide uptakes were increased in rats treated with adenine,and renal phenyl-β-D-glucuronide and hippuric acid uptakes were induced by adenine(50).These results showed that adenine(100)-induced CRF caused the reduced function of GFR-r OCTs-r MATE1 and GFR-r OAT1/r OAT3-r MRP pathway,and oppositely the renal tubular transport pathways of rOCTs-r MATE1 and rOAT1-MRPs were induced in rats with the treatment of adenine(50).展开更多
基金Supported in part by The Instituto de Salud Carlos Ⅲ,FIS (GrantPI051547)the Junta de Castilla y Leon (Grants SA021B06,SA033A08,SA03508 and SA03608)+1 种基金SpainMinisterio de Ciencia y Tecnologia,Plan Nacional de Investigacion Cientifica,Desarrollo e Innovacion Tecnologica (Grant BFU2006-12577),Spain
文摘In adults,the hepatobiliary system,together with the kidney,constitute the main routes for the elimination of several endogenous and xenobiotic compounds into bile and urine,respectively.However,during intrauterine life the biliary route of excretion for cholephilic compounds,such as bile acids and biliary pigments,is very poor.Although very early in pregnancy the fetal liver produces bile acids,bilirubin and biliverdin,these compounds cannot be efficiently eliminated by the fetal hepatobiliary system,owing to the immaturity of the excretory machinery in the fetal liver.Therefore,the potentially harmful accumulation of cholephilic compounds in the fetus is prevented by their elimination across the placenta.Owing to the presence of detoxifying enzymes and specifi c transport systems at different locations of the placental barrier,such as the endothe-lial cells of chorionic vessels and trophoblast cells,this organ plays an important role in the hepatobiliary-like function during intrauterine life.The relevance of this excretory function in normal fetal physiology is evident in situations where high concentrations of biliary compounds are accumulated in the mother.This may result in oxidative stress and apoptosis,mainly in the placenta and fetal liver,which might affect normal fetal development and challenge the fate of the pregnancy.The present article reviews current knowledge of the mechanisms underlying the hepatobiliary function of the fetal-placental unit and the repercussions of several pathological conditions on this tandem.
基金The National Natural Science Foundation of China(Grant No.81803611)Innovation and Entrepreneurship Project of the First Clinical Medical College of Lanzhou University(Grant No.20190060133)。
文摘Chronic renal failure(CRF)is a type of progressive chronic kidney disease with the alteration of substrates excretion.However,changes in renal excretion pathways remain unclear in CRF.This study aimed to evaluate the changes in renal excretion pathways of exogenous and endogenous substrates in CRF rats.Results showed that the levels of cystatin C,creatinine,and urea nitrogen were dramatically increased in the adenine(50 or 100 mg/kg)-induced CRF rats.The levels of rOCT2 were dose-dependently up-regulated by adenine,and rMRP2 and rMATE1 levels were dose-dependently down-regulated,while rMRP4 was induced by adenine(50).Plasma concentrations of metformin,p-aminohippurate,and furosemide in the adenine(100)group were significantly increased compared with the control group.However,plasma concentrations of metformin and p-aminohippurate were slightly changed in the adenine(50)group.Consistently,urinary excretions of metformin and p-aminohippurate were unaffected.In addition,renal N1-methylnicotinamide uptakes were increased in rats treated with adenine,and renal phenyl-β-D-glucuronide and hippuric acid uptakes were induced by adenine(50).These results showed that adenine(100)-induced CRF caused the reduced function of GFR-r OCTs-r MATE1 and GFR-r OAT1/r OAT3-r MRP pathway,and oppositely the renal tubular transport pathways of rOCTs-r MATE1 and rOAT1-MRPs were induced in rats with the treatment of adenine(50).
