Reye syndrome model in rats: protection against liver abnormalities by L-carnitine and acetyl-L-carnitine.
The effects of L-carnitine (LCn) and acetyl-L-carnitine (AcLCn) were assessed on the liver alterations observed in Kilpatrick's model of Reye syndrome in rats; fasted rats were given lipopolysaccharide (LPS), 0.2 mg/kg i.p., 12 hr before they were sacrificed, plus acetylsalicylic acid (ASA), 50 mg/kg i.p., 11 hr before sacrifice; LCn or AcLCn were given twice, 500 mg/kg orally, 12 and 2 hr before sacrifice. LPS+ASA-treated rats showed a dramatic decrease of hepatic ketone bodies and acetyl-CoA and an increase of isobutyryl-CoA, isovaleryl-CoA and succinyl-CoA. Electron microscopy of LPS+ASA-treated rat liver showed a slight but significant alteration in mitochondrial inner structure. Because impairment of mitochondrial function in RS is associated with swelling, we investigated whether the microviscosity of mitochondrial lipids and the cholesterol-phospholipid ratio (CHOL/PL), were involved in the RS model used. Mitochondria from LPS+ASA-treated rats showed a decrease in lipid microviscosity, in CHOL/PL ratio and in CHOL/PL ratio of both inner and outer membrane fractions; these alterations suggested a general increase in membrane fluidity. LCn and AcLCn reversed the morphological alterations in mitochondria after LPS+ASA, observed by electron microscopy, the decrease in KB and the toxic increase in short-chain acyl-CoAs; AcLCn only reversed the decrease in acetyl-CoA. LCn and AcLCn prevented mitochondrial lipid alterations mainly in the inner membrane fraction.(ABSTRACT TRUNCATED AT 250 WORDS)
D000108:Acetylcarnitine / Q000378:metabolism*; D000214:Acyl Coenzyme A / Q000378:metabolism; D000818:Animals; D001241:Aspirin / Q000633:toxicity; D002331:Carnitine / Q000378:metabolism*; D003065:Coenzyme A / Q000378:metabolism; D004195:Disease Models, Animal; D007657:Ketone Bodies / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D012202:Reye Syndrome / Q000378:metabolism* / Q000473:pathology
D000214:Acyl Coenzyme A; D007657:Ketone Bodies; D000108:Acetylcarnitine; D001241:Aspirin; D002331:Carnitine; D003065:Coenzyme A