RESEARCH ARTICLE Prevention and treatment of Schistosoma mansoni-induced liver fibrosis in mice Dina S. El-Agamy • Abdelhadi M. Shebl • Shehta A. Said Received: 22 April 2011 / Accepted: 24 August 2011 / Published online: 23 September 2011 Ó Springer Basel AG 2011 Abstract The present study was designed to examine the potential preventive and curative effects of curcumin, res- veratrol, imatinib, rosiglitazone, losartan and bosentan (BOS) on Schistosoma mansoni-induced liver fibrosis in mice. Induction of liver fibrosis was produced in male Swiss mice by subcutaneous injection of S. mansoni cercariae per mouse. Mice were left for 28 days before starting the experiment then mice were divided into two main groups. The first group was further subdivided into experimental groups and started drug treatment at day 28 after infection and continued for 2 weeks in order to evaluate the potential preventive effects of the mentioned drugs on S. mansoni- induced liver fibrosis. The second group of mice were left for 2 weeks and then treated with praziquantel for two consecutive days to eradicate the worms and so stop egg disposition and further fibrosis development. Mice were then subdivided into the experimental groups and drug treatment was started for 2 weeks to evaluate their efficacy to decrease the developed fibrosis. At the end of the experiment period, mice were killed and serum was col- lected for the estimation of alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin and albumin. Liver tissue was taken for the estimation of hepatic hydroxyproline content and histopathological examination to confirm the biochemical results. Results of the study indicate that curcumin and imatinib have potent antifibrotic activity both in suppressing and reversing S. mansoni- induced liver fibrosis, while resveratrol has beneficial effects only in suppressing the development of S. mansoni- induced liver fibrosis. Keywords Schistosoma mansoni Á Liver fibrosis Á Curcumin Á Resveratrol Á Imatinib Á Rosiglitazone Á Losartan Á Bosentan Introduction Schistosomiasis is one of the most widespread parasitic infections. Schistosoma mansoni infects tens of millions of people in many developing countries (Chitsulo et al. 2000). Hepatic fibrosis, resulting from S. mansoni infection, is of primary importance among chronic liver diseases world- wide (Mahmoud et al. 2002). The hepatosplenic schistosomiasis, the best-known form of the disease, results from chronic, heavy intestinal S. mansoni infection. The underlying cause is a periportal granulomatous inflamma- tion around parasite eggs, which are transported to the liver by portal circulation (Chang et al. 2006). The principle inflammatory response is directed against the parasite eggs, some of which enter the portal circulation and become lodged in hepatic portal venules initiating a granulomatous response. During periovular granuloma formation fibro- nectin produced by macrophages is deposited around the inflammatory cells (Andrade and Grimaud 1988) compos- ing a large part of the extracellular matrix (ECM). This is followed by the deposition of the proteoglycans dermatan sulfate, to a lesser extent heparan sulfate, and the interstitial collagen types I and III that all together form the fibrotic D. S. El-Agamy (&) Á S. A. Said Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt e-mail: dinaagamy1@yahoo.com A. M. Shebl Department of Pathology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt Inflammopharmacol (2011) 19:307–316 DOI 10.1007/s10787-011-0092-6 Inflammopharmacology 123