Intragastrically Applicated CCl4-Thiopental Sodium Enhanced Lipid Peroxidation and Liver Fibrosis (Cirrhosis) in Rat: Malonedialdehyde as a Parameter of Lipid Peroxidation Correlated with Hydroxyproline as a Parameter of Collagen Synthesis (Deposition).

We investigated the pathogenesis of liver tissue damage during the lipid peroxidation and fibrogenesis with the observation of correlations between the parameters of collagen synthesis (and deposition) and lipid peroxidation in liver fibrosis (cirrhosis) rats. Rats were randomly divided into two groups, normal and CCl4-thiopental sod. intoxicated group. And the one group was treated intragastrically with the mixture of CCl4-thiopental sod. 3 times per week for 3 weeks. The liver tissue and sera were used for the measurement of hydroxyproline (HYP), malonedialdehyde (MDA) and superoxide dismutase (SOD). Biochemical parameters such as aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total-bilirubin and blood urea nitrogen (BUN) were measured. Additionally, the expression of collagen α1(III) and β-actin mRNA was observed by RT-PCR. The histological change in liver tissue was also observed by Masson's trichrome and H&E staining. Correlation analysis was carried by Spearman's rho method. All biochemical parameters except total-bilirubin were significantly higher in the CCl4-thiopental sod. treated group than that of the normal group (p < 0.01). In the CCl4-thiopental sod. treated group, Hyp as a parameter of collagen synthesis (deposition) and MDA as a metabolite of lipid peroxidation, were significantly elevated by 1.98 and 2.11 times higher than that of the normal group (p> 0.001) respectively. The activity of SOD in the CCl4-thiopental sod. treated group is decreased significantly by 44.8% (p> 0.001). And collagen α1(III) mRNA was more expressed in the CCl4-thiopental sod. treated group than that of the normal group. However, the expression of β-actin mRNA is showed similar in both of groups. A good correlation was observed between the content of hyp and MDA concentration (r = 0.70, n = 40) in the two groups. And the correlation between the levels of hyp and SOD (r = -0.71, n = 25) is also reliable. However, no correlation were observed between MDA concentration and SOD (r = -0.40, n = 25) in the two groups. Elevated levels of MDA in CCl4-thiopental sod. treated rats indicated enhancement of lipid peroxidation, which is accompanied by a decrease in SOD activity. Moreover, we could confirm that the parameters of collagen synthesis (and deposition) is in good correlation with the metabolite of lipid peroxidation (MDA) and the lipid peroxidation antagonizing enzyme (SOD). Hence, we propose that ➀ lipid peroxidation and collagen synthesis (and deposition) could be enhanced by intragastrically application of CCl4-thiopental sod. during a short terms. And ➁ the intoxication of CCl4-thiopental sod. could be used for monitoring of lipid peroxidation and collagen synthesis (and depositon) for test of antioxidant and antifibrotic agent. © Korean Society of Toxicology 2008.