Effect of propentofylline on the biochemical lesion of the rat brain in aluminium-induced neurotoxicity.
Acute and chronic administration of Al-gluconate (12.7% Al) at the concentration of 1 mg/kg produces edema in the rat brain, as reflected by the increase in water and Na+ content. The permeability for Evans blue is also increased, which indicates the opening of the blood-brain barrier. Higher concentrations of the Al-gluconate (10 mg/kg) change, in acute experiments, the pattern of energy metabolites in the rat brain toward a profile observed in a deep hypoxia. Chronic administration of a low concentration of Al-gluconate (1 mg/kg) increases the local utilization of glucose in 20 of 39 rat brain structures examined. This increase was particularly evident in the structures of the limbic system. Xanthine derivative propentofylline reverses the edema formation in acute and chronic experiments. Hypoxia-like changes in energy metabolism are also reversed by propentofylline. In preliminary experiments propentofylline also suppressed the increased utilization of glucose observed after administration of Al-gluconate. These results suggest that (i) the Al-gluconate model in rats can be used to study Al-neurotoxicity at a very low level of Al, and (ii) the xanthine derivative propentofylline can eventually be used to abolish the Al-neurotoxicity.
Stefanovich
V
V
Hoechst AG, Werk Kalle-Albert, Wiesbaden, FRG.
Joó
F
F
D000255:Adenosine Triphosphate / Q000378:metabolism; D000535:Aluminum / Q000633:toxicity*; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects; D001929:Brain Edema / Q000139:chemically induced* / Q000188:drug therapy / Q000378:metabolism; D003837:Deoxy Sugars / Q000493:pharmacokinetics*; D003847:Deoxyglucose / Q000493:pharmacokinetics*; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D051381:Rats; D011919:Rats, Inbred Strains; D014970:Xanthines / Q000627:therapeutic use*
D003837:Deoxy Sugars; D014970:Xanthines; C032114:propentofylline; D000255:Adenosine Triphosphate; D003847:Deoxyglucose; D000535:Aluminum