Antifibrotic activity of hesperidin against dimethylnitrosamine-induced liver fibrosis in rats
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- 作者：Shimaa M. Elshazly (1)
Amr A. A. Mahmoud (1) - 关键词：Dimethylnitrosamine ; Hesperidin ; Fibrosis ; Oxidative stress ; Apoptosis ; Nitric oxide
- 刊名：Naunyn-Schmiedeberg's Archives of Pharmacology
- 出版年：2014
- 出版时间：June 2014
- 年：2014
- 卷：387
- 期：6
- 页码：559-567
- 全文大小：
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Amr A. A. Mahmoud (1)
1. Department of Pharmacology, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt - ISSN：1432-1912
文摘
Hepatic fibrosis is a significant health problem that may progress to cirrhosis and cancer. It may be caused by viruses or chemicals such as dimethylnitrosamine, which is used as a preservative in processed meats and industrial products. The present study was designed to investigate the antifibrotic effect of hesperidin (100 or 200?mg/kg, a flavanone glycoside with potent anti-inflammatory and antioxidant activities) against liver fibrosis in rats compared to silymarin (100?mg/kg). Liver fibrosis was induced in rats using dimethylnitrosamine (10?mg/kg/day, i.p.) three times per week on alternating days for 4?weeks. After 28?days, tissue and blood samples were collected to assess the protective effect of hesperidin. Dimethylnitrosamine caused liver fibrosis as evidenced by the elevation in the levels of serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total and direct bilirubin, as well as hepatic malondialdehyde content, gene expression of inducible nitric oxide synthase, α-smooth muscle actin and caspase-3. In addition, dimethylnitrosamine caused a reduction in serum total protein, albumin and hepatic glutathione content. Treatment with hesperidin (100 or 200?mg/kg) successfully ameliorated the deleterious effects of dimethylnitrosamine on all tested parameters. Our study indicates a novel protective effect of hesperidin against dimethylnitrosamine-induced liver fibrosis. Interestingly, the protection evoked by hesperidin (200?mg/kg) was superior to that of the standard silymarin.