Free radical scavengers suppress the accumulation of platinum in the cerebral cortex.
We investigated whether free radical scavengers and antioxidants inhibit the accumulation of platinum (Pt) in the cerebral cortex. Pt was detected in the cerebral cortex of mice after administration of cisplatin and exposure to short-term hypoxia. When mice were treated with either allopurinol (20 mg/kg) or catalase (100 mg/kg) before cisplatin administration and low oxygen exposure, Pt was not detected in the cerebral cortex. However, Pt was detected in the cerebral cortex of mice pretreated with either a low dosage of allopurinol or heat-denatured catalase. Furthermore, Pt was detected in the cerebral cortex of mice preadministered vitamin C, vitamin E, or deferoxamine. Lipid peroxide levels in the cerebral cortex increased 10 min after the treatment of hypoxia, and peaked 30 min after the treatment. These results suggested that short-term hypoxia produces free radicals, which allows Pt to pass through the blood-brain barrier and accumulate in the cerebral cortex, and that the production of free radicals is reduced by the administration of either allopurinol or catalase, which prevents Pt from passing through the barrier.
Minami
T
T
Department of Clinical Chemistry, Faculty of Pharmaceutical Sciences, Kinki University, Osaka, Japan.
Ichii
M
M
Okazaki
J
J
Kawaki
H
H
Okazaki
Y
Y
D000493:Allopurinol / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D002945:Cisplatin / Q000493:pharmacokinetics*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D000860:Hypoxia; D007700:Kinetics; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009525:Niacin / Q000494:pharmacology; D010984:Platinum / Q000493:pharmacokinetics*; D014810:Vitamin E / Q000494:pharmacology
D000975:Antioxidants; D016166:Free Radical Scavengers; D014810:Vitamin E; D009525:Niacin; D010984:Platinum; D000493:Allopurinol; D002374:Catalase; D001205:Ascorbic Acid; D002945:Cisplatin