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Biochemistry & Pharmacology: Open Access

Biochemistry & Pharmacology: Open Access
Open Access

ISSN: 2167-0501

+44-20-4587-4809

Abstract

Can Pharmacological Targeting of Advanced Glycation End Products Provide Protection Against Experimentally Induced Liver Fibrosis?

Baraka AM and Guemei A

Aim: The aim of the current study was to assess the possible protective effects of advanced glycation end product (AGE) inhibitors against liver fibrosis and the possible underlying mechanisms.
Material and Methods: The present study was conducted on 48 male Wistar albino rats that were grouped into six groups of 8 rats each. Groups I-III; normal groups that were injected intraperitoneally (I.P.) with normal physiological saline, and either received no treatment (Group I), or received aminoguanidine (group II) or lisinopril (group III) daily for 4 weeks by I.P. injection. Group IV included untreated liver fibrosis group in which liver fibrosis was induced by thioacetamide. Groups V and VI included treated liver fibrosis group in which aminoguandine and lisinopril were injected I.P., daily for 4 weeks, concomitantly with thioacetamide. At the end of the treatment period (4 weeks), serum was collected to measure aminotransferases (AST and ALT) activities. Hepatic levels of AGEs, transforming growth factor-B1 (TGF-β1), tissue inhibitor of matrix metalloproteinase (TIMP), malondialdehyde (MDA), reduced glutathione (GSH) and hydroxyproline levels were assessed. Histopathological examination of liver was also carried out.
Results: TAA administration resulted in hepatic fibrosis evidenced histologically and by a significant increase in hepatic hydroxyproline level. TAA also resulted in a significant increase in serum AST, ALT activities as well as hepatic AGEs, TGF-β1, MDA and TIMP concentrations, together with a significant decrease in hepatic GSH. Administration of either aminoguanidine or lisinopril resulted in significant amelioration of above mentioned parameters. Conclusion: Targeting AGEs could represent a therapeutic option for patients at risk for developing liver fibrosis.

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