Homocysteine induces oxidative stress,inflammatory infiltration,fibrosis and reduces glycogen/glycoprotein content in liver of rats |
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| Authors: | Cristiane Matté Francieli M Stefanello Vanize Mackedanz Carolina D Pederzolli Marcelo L Lamers Carlos S Dutra-Filho Marinilce F dos Santos Angela TS Wyse |
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| Institution: | 1. Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003, Porto Alegre, RS, Brazil;2. Departamento de Biologia Celular e do Desenvolvimento, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brazil |
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| Abstract: | Hyperhomocysteinemia has been related to various diseases, including homocystinuria, neurodegenerative and hepatic diseases. In the present study we initially investigated the effect of chronic homocysteine administration on some parameters of oxidative stress, named total radical-trapping antioxidant potential, total antioxidant reactivity, catalase activity, chemiluminescence, thiobarbituric acid-reactive substances, and total thiol content in liver of rats. We also performed histological analysis, evaluating steatosis, inflammatory infiltration, fibrosis, and glycogen/glycoprotein content in liver tissue sections from hyperhomocysteinemic rats. Finally, we evaluated the activities of aminotransferases in liver and plasma of hyperhomocysteinemic rats. Wistar rats received daily subcutaneous injection of Hcy from their 6th to their 28th day of life. Twelve hours after the last injection the rats were sacrificed, liver and plasma were collected. Hyperhomocysteinemia decreased antioxidant defenses and total thiol content, and increased lipid peroxidation in liver of rats, characterizing a reliable oxidative stress. Histological analysis indicated the presence of inflammatory infiltrate, fibrosis and reduced content of glycogen/glycoprotein in liver tissue sections from hyperhomocysteinemic rats. Aminotransferases activities were not altered by homocysteine. Our data showed a consistent profile of liver injury elicited by homocysteine, which could contribute to explain, at least in part, the mechanisms involved in human liver diseases associated to hyperhomocysteinemia. |
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| Keywords: | ABAP 2 2&prime -azo-bis-(2-amidinopropane) ALT alanine aminotransferase AST aspartate aminotransferase CAT catalase CBS cystathionine β-synthase CPS counts per second DTNB 5&prime -dithiobis-(2-nitrobenzoic acid) Hcy homocysteine HSC hepatic stellate cells IL interleukin MCP-1 monocyte chemoattractant protein-1 MMP matrix metalloproteinases NFκB nuclear factor kappa B PAS periodic acid-Schiff ROS reactive oxygen species SPSS statistical package for the social sciences TAR total antioxidant reactivity TBARS thiobarbituric acid-reactive substances TIMPs inhibitors of MMPs TRAP total radical-trapping antioxidant potential |
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