The development of an efficient rat hepatic cirrhosis model

Cui, Feng Ji; Choi, Sae Bul; Cho, Jin A; Lee, Ji Youn; Kim, Kyung Sik; Cho, Chang Hwan; Kim, Byong Ro

Abstract

INTRODUCTION: Applying clinical conditions to on experimental animals forto verifverifyingy the mechanism of disease and drug effects is crucial. Cirrhotic livers induced by Hepatitis B virus are frequent, and eEspecially in Korea where a great deal of more liver-related diseases occurs, cirrhotic livers induced by Hepatitis B virus are frequent, and, such viral-induced cirrhosis, and this often impedes other medical treatments. Therefore, creating a proper elucidating properly deriveding cirrhosis method in animal model to simulate the actual pathophysiology of cirrhosis can benefit future researches. AIMS: We wanted toTe testing various hypotheticalsized methods of inducing cirrhosis in animal models, and we wanted the model to have a with higher rate of reproducibility. METHOD: To induce cirrhotic liver, thioacetamide (Sigma, St. Louis, USA) wasis given either freely via oral intaken or it wasand injected into the peritoneal space ofn Sprague-Dawley(SD) rats. The SD rats wereare divided into four groups: the oOral intake gGroup 1 ((N=10, 0.03%, 13 weeks), the oOral intake gGroup 2 (N=20, 0.04%, 30 weeks), the iIntraperitoneal Injected gGroup 1 (N=10, 300mg/kg, 12 weeks (3 times per week for first 2 weeks, 2 times per week for next 10 weeks) and the iIntraperitoneal Injected gGroup 2 (N=20, 300mg/kg, 2 times per week for 16 weeks). The mMortality rate of the tested subjects is recorded, and a visual test of the livers is performed at the end of the experiment, a visual test of the livers is performed. Also, the extracted liver cells that were dyed with Trichrome are compared to evaluate the extent of the liver cirrhosis. RESULT: For theIn oral intake group 1, no loss of occurred until wWeek 13, and 5 of the SD rats (50%) showed signs of liver cirrhosis by the Trichrome dye test. However, the extent of cirrhosis greatly differed betweenfrom each of the subjects. ForIn the oral intakae group 2, no loss occurred until wWeek 30. 20 of the SD rat (100%) in this group possessed a cirrhotic liver. However, the weight of the cirrhoscirrhotic liversis differed from a minimum of 231g to a maximum of 770g. For theIn Injected Group 1, 4 tested subjects (40%) died between wWeeks 3 and 4; however, the rest of them survived and they all revealed a signs of cirrhosis. ForIn the iInjected Group 2, only 3 tested subjects (15%) died, and after wWeek 16, 17 survivors (100%) showed a signs of cirrhosis.
CONCLUSION
The short-term oral administration of thioacetamide only induced a minimal amount of cirrhosis;, thus, a longer period of consumption is suggested. Injection of thioacetamide into the peritoneum resulted in higher death rate when thoacetamide wasis injected frequently. Therefore, selecting a proper method to create a cirrhotic liver, with considering the reproducibility, on cirrhotic liver, the survival rate of the experimental animals, and the length of the experiment, isare strongly suggested for creating an animal model of cirrhotic liverfor further experiments.