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

Carageorgiou, H., Tzotzes, V., Pantos, C., Mourouzis, C., Zarros, A. and Tsakiris, S. (2004) 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. Basic and Clinical Pharmacology and Toxicology, 94(3), pp. 112-118. (doi:10.1111/j.1742-7843.2004.pto940303.x) (PMID:15049340)

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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 and Mg2+-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 vitroeffects 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 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 (5 mg/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 vivotreatment. 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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Zarros, Dr Apostolos
Authors: Carageorgiou, H., Tzotzes, V., Pantos, C., Mourouzis, C., Zarros, A., and Tsakiris, S.
Subjects:R Medicine > RB Pathology
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
R Medicine > RM Therapeutics. Pharmacology
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Basic and Clinical Pharmacology and Toxicology
Publisher:Wiley
ISSN:1742-7835
ISSN (Online):1742-7843
Published Online:12 March 2004

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