RESUMO
To study the effects of aluminium (Al) on glutathione (GSH) metabolism in the small intestine, adult male Wistar rats were orally treated with AlCl3.6H2O at doses of 30, 60, 120 and 200 mg/kg body weight (b.w.) per day, during seven days. Controls received deionized water. At doses above 120 mg/kg b.w., Al produced both a significant reduction of GSH content and an increase of oxidized/reduced glutathione ratio (P < 0.05). The index of oxidative stress of the intestine mucosa in terms of lipid peroxidation evaluated by thiobarbituric acid reactive substances was significantly increased (52%) at higher Al dose used. The duodenal expression of the multidrug resistance-associated protein 2 in brush border membranes, determined by Western blot technique, was increased 2.7-fold in rats treated with 200mg AlCl3/kg b.w (P < 0.01). Intestine activities of both GSH-synthase (from 60 mg/kg b.w.) and GSSG-reductase (from 120 mg/kg b.w.) were significantly reduced (26% and 31%, respectively) while glutathione-S-transferase showed to be slightly modified in the Al-treated groups. Conversely, gamma-glutamyltranspeptidase activity was significantly increased (P < 0.05) due to the Al treatment. Al reduced in vitro mucosa-to-lumen GSH efflux (P < 0.05). A positive linear correlation between the intestine GSH depletion and reduction of in situ 45Ca intestinal absorption, both produced by Al, was found (r = 0.923, P = 0.038). Taking as a whole, these results show that Al would alter GSH metabolism in small intestine by decreasing its turnover, leading to an unbalance of redox state in the epithelial cells, thus contributing to deteriorate GSH-dependent absorptive functions.
Assuntos
Alumínio/toxicidade , Glutationa/metabolismo , Intestinos/efeitos dos fármacos , Administração Oral , Animais , Glutationa Sintase/metabolismo , Glutationa Transferase/metabolismo , Mucosa Intestinal/metabolismo , Intestinos/enzimologia , Peroxidação de Lipídeos , Masculino , Proteínas Mitocondriais/metabolismo , Ratos , Ratos Wistar , Proteínas Ribossômicas/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
Aluminium (Al) has been recognised as a cause of bone tissue disorders. The aims of this work were to investigate: (i) whether Al affects calcium (Ca) entry into enterocyte, and (ii) the possibility that the Al effect upon calbindin-D-related Ca transport would be influenced by intestinal glutathione (GSH) levels. In isolated chicken duodenal enterocytes, 100 microM Al lactate produced a decrease in both, the maximum uptake rate and the affinity constant of 45Ca uptake (CaUPT). This effect of Al on CaUPT was concentration-dependent in the micromolar range, showing an inhibitory saturation type phenomenon which appeared to be higher at pH 6.5 than at pH 7.4, and was not modified by the Ca channel activators A23187 and capsaicin. The simultaneous administration of Al (50 mg elemental Al/kg body weight, as AlCl3) and GSH (10 mmol/kg body weight) to rats during 7 days, prevented the inhibitory effects of Al on Ca transport. The protective effect of GSH was accompanied by an increased duodenal calbindin-D9k expression. Experimental depletion of intestinal GSH by means of D,L-buthionin-[S,R] sulfoximine, a gamma-glutamylcystein-synthase inhibitor, given as a single i.p. dose of 2 mmol/kg body weight, enhanced the degree of reduction of Ca absorption ascribed to Al. Our results suggest that Al might interfere Ca uptake by enterocytes through a general effect on cell membrane, and that an oxidative stress state induced by Al would reduce intestine GSH level affecting calbindin-D function and/or synthesis, thus leading to a reduced transcellular Ca absorption in the small intestine.