Accentuation of paraquat-induced toxicity by L-carnitine in mice.
The effects of L-carnitine on toxicity induced by paraquat (PQ) in mice were investigated. L-carnitine pretreatment surprisingly promoted the toxicity of PQ in a dose-dependent manner shortening the survival time. The maximum effect occurred when L-carnitine, at a dose of 16 mmol/kg, was intraperitoneally administered 30 min before an intraperitoneal injection of PQ (75 mg/kg). Lipid peroxidation in lung significantly increased 6 h after PQ administration. L-carnitine accelerated this effect since L-carnitine-pretreated mice already showed a significant increase of lung malondialdehyde 1 h after PQ administration. In liver, PQ administration did not produce lipid peroxidation; nevertheless L-carnitine-pretreated mice showed a significant increase of malondialdehyde 6 h after PQ administration. Lung and liver glutathione decreased in mice receiving only PQ but this effect was not significantly changed by L-carnitine pretreatment. These results indicate that L-carnitine accelerates PQ-induced mortality rate by facilitating lipid peroxidation.
Unit of Pharmacology and Toxicology, Faculty of Veterinary, University of Extremadura, Cáceres, Spain.
M P
MP
Míguez
F
F
Soler
L
L
García-Rubio
D000704:Analysis of Variance; D000818:Animals; D002331:Carnitine / Q000633:toxicity*; D004357:Drug Synergism; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D051379:Mice; D010269:Paraquat / Q000633:toxicity*
D008315:Malondialdehyde; D005978:Glutathione; D010269:Paraquat; D002331:Carnitine