title: Carnitine deficiency: a possible risk factor in paracetamol hepatotoxicity.
abstract: We have addressed in the current study the postulate whether or not carnitine deficiency would represent a risk factor in hepatotoxicity. Carnitine-deficient male Swiss albino rats were obtained following administration of D-carnitine (500 mg/kg, IP) for 10 consecutive days. Serum and liver carnitine levels, both total and free, were assessed to confirm carnitine depletion. Hepatotoxicity was induced by challenging animals with a single dose of paracetamol (1 g/kg, IP). Serum tumor necrosis factor (TNF-alpha) concentration, and serum activities of aspartate amino transferase (AST), alanine amino transferase (ALT) and alkaline phosphatase (ALP) were undertaken as biomarkers for toxicity. Liver contents of reduced glutathione (GSH), malondialdehyde (MDA), total nitric oxide (NO) and myeloperoxidase (MPO) activities were also investigated. Histopathological examination of liver sections was achieved to confirm the biochemical alterations. D-carnitine altered all biochemical markers and also induced mild tissue inflammation with dilatation and congestion of central and portal veins. Paracetamol produced an obvious hepatotoxicity model that was well characterized biochemically and morphologically. Combined administration of D-carnitine and paracetamol synergistically provoked marked toxicity that was more profound than either agent given alone. The present work was further extended to elucidate any hepatoprotective effect of carnitine supplementation in such toxicity paradigm. It was apparent that L-carnitine notably ameliorated all biochemical markers and also mitigated the gross histologic alterations induced by paracetamol. Data obtained so far would suggest that carnitine deficiency could possibly be a sequela as well as a causative clue for paracetamol hepatotoxicity.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Nasr City, Cairo, Egypt. hmmarafa@yahoo.com
authors.forename: Hossam M M
authors.initials: HM
authors.lastname: Arafa
mesh_terms: D000082:Acetaminophen / Q000378:metabolism / Q000633:toxicity*; D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D018712:Analgesics, Non-Narcotic / Q000633:toxicity*; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002331:Carnitine / Q000172:deficiency*; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism* / Q000473:pathology*; D004357:Drug Synergism; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D018712:Analgesics, Non-Narcotic; D015415:Biomarkers; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D000082:Acetaminophen; D008315:Malondialdehyde; D009195:Peroxidase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D005978:Glutathione; D002331:Carnitine