chiniofon and Ataxia

The changes in lipid peroxide concentrations in plasma and tissues after subcutaneous administration of clioquinol to clioquinol-sensitive (S-rats) and -resistant neonatal rats (R-rats) were investigated. When a fixed dose of 150 mg/kg/d of clioquinol was given to R-rats for 14 d after birth, no significant difference in lipid peroxide concentrations in plasma, liver, kidney, brain and spinal cord at 5, 10 and 15 d was observed between clioquinol-treated and untreated rats. However, with increasing doses of clioquinol to R-rats every 5 d (150----300----600 mg/kg/d), the lipid peroxide concentrations at 15 d were higher in plasma, brain and spinal cord of clioquinol-treated rats than in those of untreated rats. These results suggested that repeated administrations of large doses of clioquinol to rats increased the lipid peroxides in nerve tissues. With S-rats at 5 d after birth, the lipid peroxide concentrations in liver were approximately twice those in R-rats regardless of the clioquinol administration.

Topics: Animals; Animals, Newborn; Ataxia; Body Weight; Central Nervous System; Clioquinol; Drug Resistance; Female; Hydroxyquinolines; Kidney; Lipid Peroxides; Liver; Male; Rats; Rats, Inbred Strains

The investigation was undertaken to study the neurological symptoms in rats caused by maintaining high plasma concentration of about 30 nmol/ml or more, of clioquinol. Clioquinol suspension which was prepared using polysorbate 80 was administered intraperitoneally to rats and plasma and tissue concentrations were determined. On administration of clioquinol of 100 and 200 mg/kg, the mean plasma concentrations of clioquinol reached maximum values of 30 and 58 nmol/ml, respectively, after 0.5-1 h and thereafter decreased rapidly. With 400 mg/kg, however, plasma concentration reached maximum value of about 75 nmol/ml and fell slowly. By single and repeated administration of the suspension, clioquinol was distributed in the liver and kidney at a high concentration, and also in the nervous system. In experiments on appearance of neurotoxicity in rats by repeated administration of the suspension, all of 10 rats administered intraperitoneally with 100 mg/kg/d did not develop any neurological symptoms for about 30 d. On the other hand, one of 10 and 7 of 13 rats administered with 200 and 400 mg/kg/d, respectively, developed ataxia in the hind legs or all legs on the 3rd to the 12th day after starting administration. Pathologically, a slight change of the peripheral nerve, central chromatolysis of the anterior horn neuron and severe neuronal degeneration of the Ammon's horn were observed in the rats with ataxia.

Topics: Animals; Ataxia; Clioquinol; Hydroxyquinolines; Injections, Intraperitoneal; Male; Nervous System Diseases; Rats; Rats, Inbred Strains; Time Factors