Abstract: This study aimed to investigate the ameliorative effects and molecular mechanisms of L-carnitine on lipid metabolism disorders and liver injury induced by ornidazole in Sprague-Dawley (SD) rats. Twenty-four 7-week-old specific-pathogen-free (SPF) male SD rats were randomly divided into a blank control group, an L-carnitine control group, an ornidazole model group, and an ornidazole combined with L-carnitine intervention group, and all rats were administered by gavage for 12 consecutive weeks. The results showed that the serum L-carnitine level was significantly reduced in the model group, which in turn triggered lipid metabolism disorders, elevated liver enzyme activities, and the activation of oxidative stress and inflammation. The relative content of saturated fatty acids (SFA) in the liver was increased, while the levels of monounsaturated fatty acids (MUFA) and n-3 polyunsaturated fatty acids (PUFA) were decreased, accompanied by an elevated n-6/n-3 PUFA ratio. Meanwhile, the activities of fatty acid β-oxidation enzymes and the expression of energy metabolism-related genes in the peroxisome proliferator-activated receptor α (PPARα)/adenosine monophosphate-activated protein kinase (AMPK)/silent information regulator 1 (Sirt1)/peroxisome proliferator-activated receptor γ coactivator 1α (Pgc-1α) pathway were down-regulated, and obvious pathological damage was observed in the liver tissue. After intervention with L-carnitine, the above abnormalities were significantly reversed: the serum L-carnitine level was restored, and blood lipids, liver enzyme activities, and indicators of inflammation and oxidative stress were improved; the hepatic SFA content was decreased, the levels of MUFA and n-3 PUFA were increased, and the n-6/n-3 PUFA ratio was normalized; the activities of β-oxidation enzymes and the expression of energy metabolism-related genes were up-regulated, liver pathological damage was alleviated, and most indicators returned to near-normal levels. These results indicated that L-carnitine could promote hepatic fatty acid β-oxidation and improve lipid metabolism disorders by regulating the expression of energy metabolism-related genes in the PPARα/AMPK/Sirt1/Pgc-1α pathway. Meanwhile, it could inhibit excessive inflammatory activation and alleviate oxidative stress-induced damage, thereby attenuating ornidazole-induced liver injury. This study confirms the hepatoprotective and metabolic regulatory effects of L-carnitine in a rat model of chronic ornidazole-induced liver injury, providing an experimental basis for nutritional adjuvant intervention against liver injury caused by nitroimidazole drugs.

Key words: L-carnitine; ornidazole; drug-induced liver injury; lipid metabolism; energy metabolism pathways