Aluminium increases xanthine oxidase activity and disturbs antioxidant status in the rat.
The mechanisms responsible for the neurotoxic effects of Al remain poorly understood. In order to determine whether Al promotes oxidative stress in vivo, we measured the enzymatic activity of xanthine oxidase (XO), superoxide dismutase (SOD), glutathione peroxidase (GPX), glutathione-S-transferase (GST) and glutathione reductase (GR) in four groups of rats after eight days of intraperitoneal administration of variable concentrations of Al (0, 5, 10, and 15 mg/kg body weight, respectively). XO activity was measured in both plasma and liver samples, and the activities of the remaining enzymes were further determined in the brain and red blood cells (RBC). The most significant changes were observed in XO and GPX activities, that were enhanced and depressed, respectively. In both instances, the enzyme activities were correlated with Al concentrations, either positively (XO) or negatively (GPX). Enhancement of XO and inhibition of GPX activity may lead to the accumulation of intermediate toxic compounds such as hydrogen peroxide and hydroxyl radicals, since SOD activity is increased as well. The latter finding must be taken with some caution because previous studies have shown contradictory results in this field. Our data suggest that Al toxicity could be mediated by its action on both pro- and anti-oxidant enzymes. The biological significance of these findings remains to be established.
Moumen
R
R
Equipe d'Université (Hydrolases et Cytotoxicité), Centre Hospitalier Universitaire et Université, Caen, France.
Ait-Oukhatar
N
N
Bureau
F
F
Fleury
C
C
Bouglé
D
D
Arhan
P
P
Neuville
D
D
Viader
F
F
D000535:Aluminum / Q000032:analysis / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001835:Body Weight; D001921:Brain / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000378:metabolism; D005609:Free Radicals; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D014969:Xanthine Oxidase / Q000378:metabolism*
D000975:Antioxidants; D005609:Free Radicals; D000535:Aluminum; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D005980:Glutathione Reductase; D005982:Glutathione Transferase