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.
Unit of Pharmacology and Toxicology, Faculty of Veterinary, University of Extremadura, Cáceres, Spain.
L
L
García-Rubio
A M
AM
García-Abad
F
F
Soler
M P
MP
Míguez
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