Regression of fibrosis/cirrhosis by Glycine propionyl-l-carnitine treatment in d-Galactosamine induced chronic liver damage.
OBJECTIVE
Liver fibrosis and cirrhosis are leading causes of morbidity and mortality, with majority of preventable cases attributed to excessive alcohol consumption, viral hepatitis, or non-alcoholic fatty liver disease. We previously reported the hepatoprotective effect of Glycine propionyl-l-carnitine (GPLC) against the fulminant hepatic failure (FHF) induced by d-Galactosamine (D-GalN). In this study we evaluated the protective effect of GPLC against D-GalN induced chronic liver damage.


METHODS
Animals received D-GalN twice a week for 12 weeks at a dose of 250 mg/kg body weight (BW). GPLC was given daily for 12 weeks as co-treatment along with D-GalN at a dose of 35 mg/kg BW.


RESULTS
D-GalN injection resulted in a considerable decrease in body weight, hepatocellular disintegration, necrosis and lipid peroxidation as evident from altered levels of SOD, CAT and MDA while GPLC significantly restored the reduced body weight and ameliorated hepatocellular damage and lipid peroxidation. D-GalN administration resulted in DNA damage as evident from TUNEL positive cells in disease control rats while; GPLC significantly alleviated the genotoxic effects of D-GalN. Further histopathological analysis revealed significant tissue and cellular damage, and increased collagen content in D-GalN challenged rats. GPLC however ameliorated the damage as evident from normal cellular and morphological architecture in GPLC co-treated rats. Hydroxyproline and nitrotyrosine (NTY) levels marked a significant decrease in GPLC co-treated rats relative to disease control. GPLC significantly blocked D-GalN induced pro-inflammatory cytokine (TNF-α, IL-6) production and at the same time inhibited the expression of α-smooth muscle actin (α-SMA), collagen-I (COL-I) and transforming growth factor-β (TGF-β) significantly.


CONCLUSIONS
Our results demonstrate significant protective activity of GPLC in chronic liver damage and other complications related to it. This study is a novel study to demonstrate the hepatoprotective effect of GPLC in chronic liver damage.
Department of Biotechnology, Jamia Hamdard, New Delhi, 110062, India.
Ajaz Ahmad
AA
Ganai
Department of Biotechnology, Jamia Hamdard, New Delhi, 110062, India.
Ishfaq Ahmad
IA
Ganaie
Department of Biotechnology, Jamia Hamdard, New Delhi, 110062, India.
Nishika
N
Verma
Department of Biotechnology, Jamia Hamdard, New Delhi, 110062, India. Electronic address: humbiotech@gmail.com.
Humaira
H
Farooqi
D000199:Actins / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002331:Carnitine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D002908:Chronic Disease; D024042:Collagen Type I / Q000378:metabolism; D005688:Galactosamine; D005786:Gene Expression Regulation / Q000187:drug effects; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D006909:Hydroxyproline / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced* / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017208:Rats, Wistar; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D000199:Actins; D024042:Collagen Type I; D015850:Interleukin-6; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; C002744:3-nitrotyrosine; D014443:Tyrosine; D005688:Galactosamine; C000588486:glycine propionyl carnitine; D006909:Hydroxyproline; D002331:Carnitine; D005998:Glycine
Apoptosis; Chronic liver damage; Cirrhosis; Fibrosis; Hepatic stellate cells; Oxidative stress