Effects of L-carnitine against oxidative stress in human hepatocytes: involvement of peroxisome proliferator-activated receptor alpha

We analyzed cytotoxicity using MTT assay and lactate dehydrogenase (LDH) release. Antioxidant activity and lipid peroxidation were estimated by reactive oxygen species (ROS) levels, activities and protein expressions of superoxide dismutase (SOD) and catalase (CAT), and malondialdehyde (MDA) formation. Expressions of peroxisome proliferator-activated receptor (PPAR)-alpha and its target genes were evaluated by RT-PCR or western blotting. The role of PPAR-alpha in L-carnitine-enhanced expression of SOD and CAT was also explored. Statistical analysis was performed by a one-way analysis of variance, and its significance was assessed by Dennett's post-hoc test.The results showed that L-carnitine protected HL7702 cells against cytotoxity induced by H2O2. This protection was related to the scavenging of ROS, the promotion of SOD and CAT activity and expression, and the prevention of lipid peroxidation in cultured HL7702 cells. The decreased expressions of PPAR-alpha, carnitine palmitoyl transferase 1 (CPT1) and acyl-CoA oxidase (ACOX) induced by H2O2 can be attenuated by L-carnitine. Besides, we also found that the promotion of SOD and CAT protein expression induced by L-carnitine was blocked by PPAR-alpha inhibitor MK886.Taken together, our findings suggest that L-carnitine could protect HL7702 cells against oxidative stress through the antioxidative effect and the regulation of PPAR-alpha also play an important part in the protective effect.L-carnitine (L-3-hydroxy-4-N-N-N-trimethylaminobutyrate) is an essential nutrient that the body uses to convert fat into energy. It acts as a carrier for fatty acids across the inner mitochondrial membrane for subsequent β-oxidation [1]. It is also an antioxidant that reduces metabolic stress in the cells. Studies have reported that L-carnitine have an effective 1,1-diphenyl-2-picryl-hydrazyl (DPPH) free radical scavenging, superoxide anion radical scavenging, hydrogen peroxide scavenging, and total reducing power [2].Recent years L-