The Effect Of Sodium Nitrite On Chronic Alcoholic Liver Fibrosis

Chronic expose to alcohol could result in the generation of a large amount of reactive oxygenspecies （ROS）, and induce per-oxidative stress, which cause liver injury and inability of liver cells to repairthe injury. In addition, Lupffer cells and astrocytes could be activated and become more proliferative. Thereare more collagen production and hepatic lobules segmentation, which could induce hepatofibrosis or evenhepatocirrhosis. Therefore, impediment of the peroxidation in liver, inhibition of peroxidative stress couldbe promising ways to defer or prevent hepatofibrosis. Recent studies have shown that sodium nitrite couldbecome nitric oxygen under acidic context, which inhibits mitochondrial function directly or indirectly, andcould reduce the production of ROS and prevent oxidative stress. Theoretically, low dose sodium nitritecould interfere alcoholic liver injury via production of NO.To study the protective function of sodium nitrite to alcoholic liver disease, and the potentialmechanism under it,40male mice were used. They were randomly divided into four groups, which werecontrol group, sodium nitrite only group, alcohol group and sodium nitrite plus alcohol group. Each grouphas10mice. For sodium nitrite plus alcohol group, the mice were treated with sodium nitrite (gavage,0.02ml.g^-1,800mg.l^-1) in the evening for20weeks. In the next morning,12hours later, they were treatedwith25%alcohol (0.02ml.g^-1). For alcohol group, the mice were treated with saline in the evening, andthen were treated with alcohol in the next morning.20weeks later, animals were sacrificed, and blood andliver tissue were collected for examination in the following steps.As a result, we found that the expression of ALT or AST in sodium nitrite plus alcohol groupwere much lower than alcohol group, but the CAT and SOD were higher than alcohol group. In control andsodium nitrite only group, the hepatic lobules are intact, and the profile of hepatic sinusoids is clear. Alsothere are less apoptotic hepatocytes in those groups. However, there is more tissue damage in sodium nitriteplus alcohol group, and there are less apoptosis cells. Moreover, the fibrous tissue in hepatic sinusoidappears in alcohol group, while the sodium nitrite plus alcohol group only shows little amount fibroustissue. The expression level of albumn or fiber special protein （FSP） is lower in alcohol group than sodiumnitrite plus alcohol group. In addition, hypoxia inducible factor （HIF1-α） was high in alcohol group and was much lower when treated with sodium nitrite in sodium nitrite plus alcohol group.Conclusion: I. Sodium nitrite holds a protective function to chronic alcoholic injury in liver. II.Sodium nitrite could inhibit the progression of hepatofirosis. III. Chronic alcohol exposure can induce ETMand hepatofibrosis. IV. Reduced production of ROS, decreased activity of anti-oxidase and HIF^-1α mightinvolve in the inhibitive effect of sodium nitrite to hepatofibrosis caused by chronic expose to alcohol.