Long-term Alcohol Consumption Increases Pro-Matrix Metalloproteinase-9 Levels via Oxidative Stress

Abstract

Matrix metalloproteinases (MMPs) play an important role in alcoholic liver disease. In this study, we evaluated the relationship between pro MMP-9 (pMMP-9) and oxidative stress in plasma of rat exposed to chronic alcohol consumption. Twenty four rats were divided into four groups. Rats in the control group (n=6) were subjected to physiologic saline by intragastric (i.g.) route. Group Ethanol (n=6) was given 1 ml of 80% ethanol (v/v) in distilled water through i.g. route. Group Vitamin E (Vit E), (n=6) was given vitamin E (100 mg kg-1 day-1) by intra peritonealy. Group Vitamin E+Ethanol (n=6) was given vitamin E 2 h before the administration of ethanol. At the end of 4 weeks, blood samples were taken and plasma malondialdehyde (MDA), protein carbonyls (PCs), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α) and pMMP-9 levels were measured. Chronic ethanol administration increased the AST, MDA, PCs, TNF-α and pMMP-9 levels when compared to those in control group (p<0.05, p<0.01, p<0.01, p<0.05, p<0.05, respectively). Vitamin E treatment was found to decrease lipid peroxidation and protein oxidation (p<0.01, p<0.01, respectively). Also TNF-α and pMMP-9 levels returned to normal by vitamin E treatment. Within all subjects, there was positive correlation between pMMP-9 levels and MDA, PCs levels (p=0.045, r=0.454; p=0.004, r=0.574, respectively). We conclude that since antioxidant supplementation decreases the alcohol-induced pMMP-9 levels, oxidative stress could be one of the mediators of the generation of MMP-9. © 2010 American College of Medical Toxicology.