Glutathione depleting drugs, antioxidants and intestinal calcium absorption

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 Ca(2+) absorption. The use of GSH depleting drugs such as DL-buthionine-S,R-sulfoximine, menadione or vitamin K(3), sodium deoxycholate or diets enriched in fructose, which induce several features of the metabolic syndrome, produce inhibition of the intestinal Ca(2+) 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 Ca(2+) transport or the paracellular Ca(2+) route are altered by GSH depleting drugs. The gene and/or protein expression of transporters involved in the transcellular Ca(2+) pathway are decreased. The flavonoids quercetin and naringin highly abrogate the inhibition of intestinal Ca(2+) 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 Ca(2+) transport caused by GSH depleting drugs. The use of any of these antioxidants to ameliorate the intestinal Ca(2+) absorption under oxidant conditions associated with different pathologies in humans requires more investigation with regards to the safety, pharmacokinetics and pharmacodynamics of them.