title: Aluminium-induced impairment of transcellular calcium absorption in the small intestine: calcium uptake and glutathione influence.
abstract: 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.
authors.affiliation: Laboratorio de Investigaciones Fisiológicas Experimentales, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Piso 4, Ciudad Universitaria, Paraje El Pozo (3000) Santa Fe, Argentina. orihuela@fbcb.unl.edu.ar
authors.forename: Daniel
authors.initials: D
authors.lastname: Orihuela
authors.forename: Verónica
authors.initials: V
authors.lastname: Meichtry
authors.forename: Manuel
authors.initials: M
authors.lastname: Pizarro
mesh_terms: D000535:Aluminum / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002645:Chickens; D005978:Glutathione / Q000378:metabolism*; D007408:Intestinal Absorption / Q000187:drug effects*; D007421:Intestine, Small / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002120:Calcium Channel Agonists; D000535:Aluminum; D005978:Glutathione; D002118:Calcium