Protective Effect of Pentoxifylline and Ciprofloxacin on Dimethylnitrosamine-induced Hepatic Fibrosis in Rats

Korean J Hepatol > Volume 7(1); 2001 > Article

The Korean Journal of Hepatology 2001;7(1): 34-46.

원저 / Dimethylnitrosamine에 의한 백서의 간섬유화 과정에서 Pentoxifylline과 Ciprofloxacin의 영향 ( Protective Effect of Pentoxifylline and Ciprofloxacin on Dimethylnitrosamine-induced Hepatic Fibrosis in Rats )

Protective Effect of Pentoxifylline and Ciprofloxacin on Dimethylnitrosamine-induced Hepatic Fibrosis in Rats

Kang Suek Suh,Chang Hun Lee,Mee Young Sol,Sun Kyung Lee

Department of Pathology, College of Medicine, Pusan National University

ABSTRACT

Background/Aims
Hepatic fibrosis is known to be a predisposing condition of cirrhosis for which there is no proven effective therapy. The aim of this study was to investigate the effect of pentoxifylline and ciprofloxacin on biochemical and histological features of rat hepatic fibrosis induced by dimethylnitrosamine (DMN). Methods: Seventy male Sprague-Dawley rats were divided into four groups including control (n = 10), DMN (n = 20), DMN plus pentoxifylline (n = 20) and DMN plus ciprofloxacin (n = 20). The rats were injected intraperitoneally with normal saline in the control group and the aforementioned chemicals in the study groups three times a week for 3 weeks. Two rats of the control group, and fives of each study group were sacrificed weekly after the beginning of experiment. From sacrified rats the following parameters of hepatic fibrosis were determined: AST, ALT, cytokines IL-1β, TNF-α and INF-γ, and histological features of hepatic tissue. Result: Rat weight, serological and histological findings were distinctively improved in two treated groups compared with untreated DMN group(p<0.05), The antifibrogenic activity between treated groups was rather better in the group treated with pentoxifylline than in the group treated with ciprofloxacin. During the first and second weeks after experiment the distribution of hepatic stellate cells in treated groups was limited, whereas DMN group showed their diffuse distribution. At the third week DMN group displayed micronodular cirrhosis, but treated groups showed only mild centrilobular fibrotic areas without developing cirrhosis. Conclusion: Our results indicate that pentoxifylline and cirprofloxacin may be protective against DMN induced rat hepatic fibrogenesis, while accompanying the inhibition of hepatic stellate cells during the early stage of hepatic fibrogenesis.(Korean J Hepatol 2001;7:34-46)

KeyWords: Hepatic fibrosis, Dimethylnitrosamine, Pentoxifylline, Ciprofloxacin, Hepatic stellate cell