Short-term oral exposure to aluminium decreases glutathione intestinal levels and changes enzyme activities involved in its metabolism.
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.
Orihuela
Daniel
D
Cátedra de Fisiología Humana, Laboratorio de Investigaciones Fisiológicas Experimentales, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Ciudad Universitaria, Santa Fe, Argentina. orihuela@fbcb.unl.edu.ar
Meichtry
Verónica
V
Pregi
Nicolás
N
Pizarro
Manuel
M
D000284:Administration, Oral; D000535:Aluminum / Q000633:toxicity*; D000818:Animals; D005978:Glutathione / Q000378:metabolism*; D005981:Glutathione Synthase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects* / Q000201:enzymology; D015227:Lipid Peroxidation; D008297:Male; D024101:Mitochondrial Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012269:Ribosomal Proteins / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
C093947:MRP2 protein, S cerevisiae; D024101:Mitochondrial Proteins; D012269:Ribosomal Proteins; D029701:Saccharomyces cerevisiae Proteins; D017392:Thiobarbituric Acid Reactive Substances; D000535:Aluminum; D005982:Glutathione Transferase; D005981:Glutathione Synthase; D005978:Glutathione