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World J Gastroenterol. Nov 28, 2018; 24(44): 4979-4988
Published online Nov 28, 2018. doi: 10.3748/wjg.v24.i44.4979
Glutathione depleting drugs, antioxidants and intestinal calcium absorption
Luciana Moine, María Rivoira, Gabriela Díaz de Barboza, Adriana Pérez, Nori Tolosa de Talamoni
Luciana Moine, María Rivoira, Gabriela Díaz de Barboza, Adriana Pérez, Nori Tolosa de Talamoni, Laboratorio “Dr. Fernando Cañas”, Cátedra de Bioquímica y Biología Molecular, Facultad de Ciencias Médicas, INICSA (CONICET-Universidad Nacional de Córdoba), Córdoba 5000, Argentina
Author contributions: Moine L, Rivoira M, Díaz de Barboza G, Pérez A and Tolosa de Talamoni NT participated in information collection, analysis, information organization, writing, figure design, and final editing.
Conflict-of-interest statement: No conflicts of interest, financial or otherwise, are declared by the authors.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author to: Nori Tolosa de Talamoni, PhD, Professor, Laboratorio “Dr. Fernando Cañas”, Cátedra de Bioquímica y Biología Molecular, Facultad de Ciencias Médicas, INICSA (CONICET-Universidad Nacional de Córdoba), Pabellón Argentina, 2do. Piso, Ciudad Universitaria, Córdoba 5000, Argentina. ntolosa@biomed.fcm.unc.edu.ar
Telephone: +54-351-4333024
Received: August 28, 2018
Peer-review started: August 28, 2018
First decision: October 9, 2018
Revised: October 24, 2018
Accepted: November 2, 2018
Article in press: November 2, 2018
Published online: November 28, 2018
Abstract

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.

Keywords: Glutathione, Transcellular and paracellular Ca2+pathways, DL-buthionine-S,R-sulfoximine, Fructose rich diet, Menadione, Sodium deoxycholate, Glutamine, Ursodeoxycholic acid, Melatonin, Quercetin, Naringin

Core tip: The normal content of glutathione (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 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.