Glycine propionyl l-carnitine attenuates d-Galactosamine induced fulminant hepatic failure in wistar rats

Chem Biol Interact. 2014 May 5:214:33-40. doi: 10.1016/j.cbi.2014.02.006. Epub 2014 Feb 22.

Abstract

Glycine propionyl l-carnitine (GPLC) is a propionyl ester of carnitine that includes an additional glycine component. The present study evaluated hepatoprotective effect of GPLC in d-Galactosamine (d-GalN) induced fulminant hepatic failure. Rats were intraperitonially administered d-GalN (700mg/kgBW). GPLC was given as a pre-treatment (35mg/kgBW/day) for 1month followed by a single dose of d-GalN on the 31st day. d-GalN administration resulted in increased mortality and serum ALT and AST activities. These increases were significantly attenuated by GPLC. d-GalN treatment increased hepatic lipid peroxidation and a decrease in reduced glutathione content was observed. GPLC pre-treatment significantly decreased lipid peroxidation and augmented the level of GSH. d-GalN increased the circulating level of TNF-α and ATM-Kinase and MAP-Kinase expression. GPLC supplementation inhibited the increase in serum TNF-α and ATM-Kinase and MAP-Kinase expression. d-GalN treatment increased the level of Bax and Caspase-3 m-RNA while as a decline was observed in Bcl2 m-RNA. GPLC prevented the increase in Caspase-3 and Bax m-RNA and at the same time augmented the expression of Bcl2 m-RNA. Our findings suggest that GPLC alleviates d-GalN induced liver injury by strengthening antioxidative defense system and reducing apoptotic signalling pathways.

Keywords: Inflammation; Lipid peroxidation; Liver damage; Oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Aspartate Aminotransferases / blood
  • Ataxia Telangiectasia Mutated Proteins / metabolism
  • Base Sequence
  • Carnitine / analogs & derivatives*
  • Carnitine / pharmacology
  • Comet Assay
  • DNA Primers
  • Galactosamine / toxicity*
  • Glutathione / blood
  • Glycine / analogs & derivatives*
  • Glycine / pharmacology
  • Lipid Peroxidation
  • Liver Failure, Acute / chemically induced
  • Liver Failure, Acute / prevention & control*
  • Male
  • Mitogen-Activated Protein Kinases / metabolism
  • Rats
  • Rats, Wistar
  • Real-Time Polymerase Chain Reaction
  • Tumor Necrosis Factor-alpha / blood

Substances

  • DNA Primers
  • Tumor Necrosis Factor-alpha
  • Galactosamine
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Ataxia Telangiectasia Mutated Proteins
  • Mitogen-Activated Protein Kinases
  • Glutathione
  • glycine propionyl carnitine
  • Carnitine
  • Glycine