Lack of inducible nitric oxide synthase leads to increased hepatic apoptosis and decreased fibrosis in mice after chronic carbon tetrachloride administration
✍ Scribed by Ghazaleh Aram; James J. Potter; Xiaopu Liu; Michael S. Torbenson; Esteban Mezey
- Publisher
- John Wiley and Sons
- Year
- 2008
- Tongue
- English
- Weight
- 696 KB
- Volume
- 47
- Category
- Article
- ISSN
- 0270-9139
No coin nor oath required. For personal study only.
✦ Synopsis
The role of nitric oxide (NO) in liver injury and fibrosis is unclear. The purpose of this study was to determine whether inducible NO synthase deficiency (iNOS(-/-)) affects liver injury and fibrosis produced in mice by chronic carbon tetrachloride (CCl(4)) administration. Wild-type (WT) or iNOS(-/-) mice were subjected to biweekly CCl(4) injections over 8 weeks, whereas controls were given isovolumetric injections of olive oil. Serum aminotransferases were lower after CCl(4) in the iNOS(-/-) than in the WT mice, which correlated with decreased necrosis on liver histology. There was increased apoptosis, a lower number of stellate cells, and a lesser degree of fibrosis after CCl(4) in the iNOS(-/-) as compared with the WT mice. alpha(1)(I) collagen messenger RNA (mRNA) was markedly increased after CCl(4) in the WT and to a significantly lesser extent in the iNOS(-/-) mice. Liver matrix metalloproteinase-9 (MMP-9) mRNA and MMP-2 mRNA were increased more in the WT than in the iNOS(-/-) mice after CCl(4). Also tissue inhibitor metalloproteinase 1 (TIMP-1) mRNA was increased to a much greater extent in the WT than in the iNOS(-/-) mice after CCl(4) (P < 0.05). However, MMP-9 and TIMP-1 protein, determined by western blot, were similarly increased after CCl(4) in both groups of mice.
Conclusion:
No protects against ccl(4)-induced apoptosis. in the absence of inos, there is decreased necrosis, increased apoptosis, and reduced liver fibrosis.