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 a ssessed on the liver alterations observed in Kilpatrick's model of Rey e 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-t reated rats showed a dramatic decrease of hepatic ketone bodies and ac etyl-CoA and an increase of isobutyryl-CoA, isovaleryl-CoA and succiny l-CoA. Electron microscopy of LPS+ASA-treated rat liver showed a sligh t but significant alteration in mitochondrial inner structure. Because impairment of mitochondrial function in RS is associated with swellin g, 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 decrea se in lipid microviscosity, in CHOL/PL ratio and in CHOL/PL ratio of b oth inner and outer membrane fractions; these alterations suggested a general increase in membrane fluidity. LCn and AcLCn reversed the morp hological alterations in mitochondria after LPS+ASA, observed by elect ron microscopy, the decrease in KB and the toxic increase in short-cha in acyl-CoAs; AcLCn only reversed the decrease in acetyl-CoA. LCn and AcLCn prevented mitochondrial lipid alterations mainly in the inner me mbrane fraction. We conclude that supplementation with LCn and AcLCn t o animals treated with LPS+ASA is beneficial, probably because it perm its fuel production, prevents accumulation of toxic compounds and stab ilizes mitochondrial membranes. Whether carnitine has a protective rol e on human RS and Reye-like syndromes has still to be proved.