Glutathione depleting drugs, antioxidants and intestinal calcium absorption  

作　　者：Luciana Moine María Rivoira Gabriela Díaz de Barboza Adriana Pérez Nori Tolosa de Talamoni 

机构地区：[1]Laboratorio "Dr. Fernando Canas", Cátedra de Bioquímica y Biología Molecular, Facultad de Ciencias Médicas, INICSA (CONICET-Universidad Nacional de Córdoba), Córdoba 5000, Argentina

出　　处：《World Journal of Gastroenterology》2018年第44期4979-4988,共10页世界胃肠病学杂志（英文版）

摘　　要：Glutathione （GSH） is a tripeptide that constitutes one of the main intracellular reducing compounds. The normal content of GSH in the intestine is essential to optimize the intestinal Ca2＋ absorption. The use of GSH depleting drugs such as DL-buthionine-S,R-sulfoximine, menadione or vitamin K3, sodium deoxycholate or diets enriched in fructose, which induce several features of the metabolic syndrome, produce inhibition of the intestinal Ca2＋ ab-sorption. The GSH depleting drugs switch the redox state towards an oxidant condition provoking oxida-tive/nitrosative stress and inflammation, which lead to apoptosis and/or autophagy of the enterocytes. Either the transcellular Ca transport or the paracellular Ca route are altered by GSH depleting drugs. The gene and/or protein expression of transporters involved in the transcellular Ca2＋ pathway are decreased. The favonoids quercetin and naringin highly abrogate the inhibition of intestinal Ca2＋ absorption, not only by restoration of the GSH levels in the intestine but also by their anti-apoptotic properties. Ursodeoxycholic acid, melatonin and glutamine also block the inhibition of Ca2＋ transport caused by GSH depleting drugs. The use of any of these antioxidants to ameliorate the intestinal Ca2＋ absorption under oxidant conditions associated with different pathologies in humans requires more investigation with regards to the safety,pharmacokinetics and pharmacodynamics of them.Glutathione(GSH) is a tripeptide that constitutes one of the main intracellular reducing compounds. The normal content of GSH in the intestine is essential to optimize the intestinal Ca2+ absorption. The use of GSH depleting drugs such as DL-buthionine-S,R-sulfoximine, menadione or vitamin K3, sodium deoxycholate or diets enriched in fructose, which induce several features of the metabolic syndrome, produce inhibition of the intestinal Ca2+ absorption. The GSH depleting drugs switch the redox state towards an oxidant condition provoking oxidative/nitrosative stress and inflammation, which lead to apoptosis and/or autophagy of the enterocytes. Either the transcellular Ca2+ transport or the paracellular Ca2+ route are altered by GSH depleting drugs. The gene and/or protein expression of transporters involved in the transcellular Ca2+ pathway are decreased. The flavonoids quercetin and naringin highly abrogate the inhibition of intestinal Ca2+ absorption, not only by restoration of the GSH levels in the intestine but also by their anti-apoptotic properties. Ursodeoxycholic acid, melatonin and glutamine also block the inhibition of Ca2+ transport caused by GSH depleting drugs. The use of any of these antioxidants to ameliorate the intestinal Ca2+ absorption under oxidant conditions associated with different pathologies in humans requires more investigation with regards to the safety, pharmacokinetics and pharmacodynamics of them.

关 键 词：GLUTATHIONE Transcellular and paracellular Ca^2＋pathways DL-buthionine-S R-sulfoximine Fructose rich diet MENADIONE Sodium deoxycholate Glutamine Ursodeoxycholic acid Melatonin Quercetin NARINGIN 

分 类 号：R96[医药卫生—药理学]