Cytotoxicity of paraquat in freshly isolated rat hepatocytes: effects of L-carnitine.
The effects of L-carnitine, a mitochondrial carrier of fatty acids, on paraquat (PQ) cytotoxicity in freshly isolated rat hepatocytes were studied. Addition of PQ (10 mM) to hepatocytes resulted in a time-dependent depletion of intracellular glutathione (GSH) accompanied by an increase in accumulation of malondialdehyde (MDA) in the incubation medium which proceeded to a loss of cell viability. Pretreatment of hepatocytes with L-carnitine (50-mM) alone did not affect cell viability or intracellular levels of GSH, or accumulation of MDA in the medium during the incubation period; however, pretreatment with L-carnitine 30 min prior to PQ addition did promote the depletion of intracellular GSH and MDA accumulation induced by PQ, and ultimately enhanced the cytotoxicity of PQ.
García-Rubio
L
L
Unit of Pharmacology and Toxicology, Faculty of Veterinary, University of Extremadura, Cáceres, Spain.
García-Abad
A M
AM
Soler
F
F
Míguez
M P
MP
D000818:Animals; D002331:Carnitine / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005978:Glutathione / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D010269:Paraquat / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
D008315:Malondialdehyde; D005978:Glutathione; D010269:Paraquat; D002331:Carnitine