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 |
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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 > School 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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