Melatonin not only restores but also prevents the inhibition of the intestinal Ca2+ absorption caused by glutathione depleting drugs

Abstract

We have previously demonstrated that melatonin (MEL) blocks the inhibition of the intestinal Ca2+ absorption caused by menadione (MEN). The purpose of this study were to determine whether MEL not only restores but also prevents the intestinal Ca2+ absorption inhibited either by MEN or BSO, two drugs that deplete glutathione (GSH) in different ways, and to analyze the mechanisms by which MEN and MEL alter the movement of Ca2+ across the duodenum. To know this, chicks were divided into four groups: 1) controls, 2) MEN treated, 3) MEL treated, and 4) treated sequentially with MEN and MEL or with MEN and MEL at the same time. In a set of experiments, chicks treated with BSO or sequentially with BSO and MEL or with BSO and MEL at the same time were used. MEL not only restored but also prevented the inhibition of the chick intestinal Ca2+ absorption produced by either MEN or BSO. MEN altered the protein expression of molecules involved in the transcellular as well as in the paracellular pathway of the intestinal Ca2+ absorption. MEL restored partially both pathways through normalization of the O2- levels. The nitrergic system was not altered by any treatment. In conclusion, MEL prevents or restores the inhibition of the intestinal Ca2+ absorption caused by different GSH depleting drugs. It might become one drug for the treatment of intestinal Ca2+ absorption under oxidant conditions having the advantage of low or null side effects.