title: Aqueous garlic extract alleviates liver fibrosis and renal dysfunction in bile-duct-ligated rats.
abstract: There is accumulating evidence that the renin-angiotensin system (RAS) is involved in hepatic inflammation and fibrogenesis. Garlic was found to lower the activity of the angiotensin converting enzyme (ACE) in the serum of rats in a diabetic model. We examined the effect of an aqueous garlic extract (AGE) on the ACE activity, cholestasis-induced liver fibrosis, and associated renal dysfunction in comparison with the effect of the standard drug enalapril. Both AGE and enalapril were administered orally for six weeks starting from the third day after bile duct ligation (BDL). BDL significantly increased the serum activities of liver enzymes, serum lactate dehydrogenase (LDH) activity, an indicator of liver cell death, serum total bilirubin (TB) level, liver myeloperoxidase (MPO) activity, and liver malondialdehyde (MDA) content. BDL was associated with elevation of serum urea and creatinine levels indicating renal dysfunction. BDL also caused an increase in the transcript levels of the genes coding for tumour necrosis factor alpha (TNF-alpha), transforming growth factor beta-1 (TGF-beta1), and matrix metalloproteinase-13 (MMP-13), a collagenase, in liver tissues. A significant decrease in hepatic reduced glutathione (GSH) was observed in BDL rats, while serum ACE activity was increased. Both AGE and enalapril counteracted all these deleterious changes, with the exception that only AGE reduced the MPO activity. These findings suggest that AGE possesses hepato- and renoprotective properties, similar to enalapril, probably by modulating the levels of proteins such as TNF-alpha, TGF-beta1 and MMP-13, and involving a reduction of ACE and of oxidative stress.
authors.forename: Mona F
authors.initials: MF
authors.lastname: Mahmoud
authors.forename: Sara
authors.initials: S
authors.lastname: Zakaria
authors.forename: Ahmed
authors.initials: A
authors.lastname: Fahmy
mesh_terms: D000110:Acetylcholinesterase / Q000097:blood; D000818:Animals; D001483:Base Sequence; D001652:Bile Ducts / Q000601:surgery*; D016923:Cell Death / Q000187:drug effects; D017931:DNA Primers; D005737:Garlic / Q000737:chemistry*; D005978:Glutathione / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D053509:Matrix Metalloproteinase 13 / Q000235:genetics; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053773:Transforming Growth Factor beta1 / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D014867:Water
chemical_list: D017931:DNA Primers; D010936:Plant Extracts; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D014867:Water; D008315:Malondialdehyde; D000110:Acetylcholinesterase; D053509:Matrix Metalloproteinase 13; D005978:Glutathione