title: In vivo and in vitro effects of cadmium on adult rat brain total antioxidant status, acetylcholinesterase, (Na+, K+)-ATPase and Mg2+-ATPase activities: protection by L-cysteine.
abstract: This study was undertaken in order to investigate a) the short- and long-term in vivo effects of cadmium (Cd) on brain acetylcholinesterase (AChE), (Na+, K+)-ATPase activities in adult rats, b) the concentration-dependent in vitro and in vivo (acute experiment) effects of Cd on the activity of those enzymes, c) the in vivo and in vitro effects of the antioxidant L-cysteine (Cys) on the above enzyme activities, and d) the evaluation of brain total antioxidant status after in vivo Cd, L-cysteine, or L-cysteine+Cd administration in rats. In vitro, CdSO4 inhibited pure and brain AChE in concentrations higher than 0.1 mM, while it activated by approximately 70% (P<0.001) brain Na+, K+ -ATPase in concentrations up to 0.1 mM and inhibited its activity in higher concentrations. Mg2+ -ATPase was not influenced up to 0.1 mM concentration, while it was inactivated (40%, P<0.001) in higher CdSO4 concentrations. A dose-response study of brain CdSO4 (1,2 and 5 mg/kg once 8 hr before decapitation) revealed a dose-dependent decrease (-14 to -30%, P<0.001) of brain AChE activity, an increase of Na+, K+ -ATPase activity (+47 to +200%, P<0.001) and an increase of Mg2+ -ATPase only after the highest dose (5mg/kg) in the short-term treatment of rats. Long-term Cd administration (1 mg/kg rat daily for 4 months) activated brain AChE and Na+, K+ -ATPase about 50-65% (P<0.001) but not Mg2+ -ATPase. Brain total antioxidant status was decreased by Cd (30%, P<0.01), while it was increased by L-cysteine or L-cysteine+Cd (50%, P<0.001) in the short-term in vivo treatment. L-cysteine reversed the enzymatic activity changes observed with Cd alone in the high-dose short-term in vivo treatment of rats, as well as the brain AChE inhibition induced by Cd in the in vitro experiments. These results indicate that: a) Cd can influence in a different way the examined enzyme activities after short- and long-term administration, b) Cd may modulate brain cholinergic mechanism(s), neural excitability and metabolic energy production, and c) L-cysteine can have a protective antioxidant effect on the oxidative stress of the brain induced by Cd.
authors.affiliation: Department of Experimental Pharmacology, Medical School, University of Athens, Athens, Greece.
authors.forename: Haris
authors.initials: H
authors.lastname: Carageorgiou
authors.forename: Vassilios
authors.initials: V
authors.lastname: Tzotzes
authors.forename: Constantinos
authors.initials: C
authors.lastname: Pantos
authors.forename: Constantinos
authors.initials: C
authors.lastname: Mourouzis
authors.forename: Apostolos
authors.initials: A
authors.lastname: Zarros
authors.forename: Stylianos
authors.initials: S
authors.lastname: Tsakiris
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism; D002104:Cadmium / Q000633:toxicity*; D003545:Cysteine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D004785:Environmental Pollutants; D002104:Cadmium; D000110:Acetylcholinesterase; D000251:Adenosine Triphosphatases; D017301:Ca(2+) Mg(2+)-ATPase; D000254:Sodium-Potassium-Exchanging ATPase; D003545:Cysteine