Lycopene prevents mitochondrial dysfunction during D-galactosamine/lipopolysaccharide induced fulminant hepatic failure in albino rats.
J Proteome Res. 2017 Jul 31. Epub 2017 Jul 31. PMID: 28758404
Sheik Abdulazeez Sheriff
Fulminant hepatic failure (FHF) is a serious health issue, with a high mortality rate and characterized by severe perturbation in mitochondrial function. D-Galactosamine/lipopolysaccharide (D-GalN/LPS) induced FHF is a renowned model to evaluate the efficacy of hepatoprotective agents. Lycopene is an antioxidant and phytonutrient from carotenoid family. The health benefits of lycopene are prominent against cancer, cardiovascular, lung, liver, and skin problems. Recent studies have demonstrated the hepatoprotective, antidyslipidemic, and antioxidant roles of lycopene. In this context, the present study was designed to evaluate the ability of lycopene to prevent the mitochondrial dysfunction during the D-GalN/LPS induced FHF. The administration of D-GalN/LPS (300 mg and 30µg /kg body weight respectively) to the experimental rats induced several disturbances in mitochondrial function. The lipid and hydrogen peroxide levels were increased (p<0.05) with concomitant decrease in the activities of mitochondrial antioxidants, citric acid or tricarboxylic acid (TCA) cycle and electron transport chain enzymes. The cellular Adenosine triphosphate (ATP) content was also found to be decreased (p<0.05). lycopene (10 mg/kg body weight for 6 days) pretreatment attenuated lipid peroxidation and prohibited the excessive production of hydrogen peroxide. The D-GalN/LPS induced impairment in ATP production and increased enzyme activities were effectively prevented by the lycopene administration. The lycopene mediated mitochondrial protection was mainly ascribed to the strong antioxidant potential of this phytonutrient. Molecular modeling results obtained show evidence that lycopene inhibits several lipoxygenases provides rationale to the observed prevention of lipid peroxidation in the mitochondrial membrane. The carotenoid lycopene, combated oxidative stress, scavenged free radicals, prevented ROS generation, and inhibited the toxic effects of D-GalN/LPS during FHF.