Aim: The present study was a preliminary trial evaluating the possible antifibrotic effect of pentoxifylline on experimentally induced schistosomal hepatic fibrosis and, also, to investigate its effect on serum leptin and transforming growth factor-β1 levels as possible antifibrotic mechanisms in correlation with the hepatic fibrosis indices. Methods: In the study, ninety Swiss, laboratory bred parasite free, albino mice of both sexes were included. Ten mice served as a control non-infected, nontreated group and sacrificed at one time. The remaining 80 mice were infected subcutaneously with 50 Schistosoma mansoni cercariae/mouse and classified into the following groups: Group I (infected & non-treated), group II (infected & treated with praziquantel), group III (infected & treated with pentoxifylline) and group IV (infected & treated with a combination of praziquantel and pentoxifylline). Each group was further subdivided into 2 subgroups; subgroup 'a' which started treatment at 6 th week post-infection (P.I.) and sacrificed at the end of 9 th week P.I and subgroup 'b' which started treatment at 14 th week P.I and sacrificed at the end of 17 th week P.I. The efficacy of the treatment was assessed by histopathological examination of the liver with measurement of granuloma size, estimation of hydroxyproline content in the liver, and assessment of serum levels of leptin and transforming growth factor-ß1 (TGF-ß1). Results: Praziquantel (PZQ) caused significant reductions in granuloma sizes and hepatic hydroxyproline content and caused non-significant reductions in serum levels of leptin and transforming growth factor-ß1 at the 9 th & 17 th weeks P.I (group II). Pentoxifylline (PTX) caused significant reductions in granuloma size, hepatic hydroxyproline, and serum levels of leptin and transforming growth factor-ß1 at the 9 th & 17 th weeks P.I (group III). Combined therapy of both PZQ & PTX in group IV caused more reductions in granuloma size, hepatic hydroxyproline, and serum levels of leptin and TGF-ß1 at the 9th & 17th weeks P.I when compared to the other groups. Conclusion: Pentoxifylline (PTX) is a promising antifibrotic drug, acting by reducing serum TGF-ß1 and leptin levels in the experimental schistosomal hepatic fibrosis. Also, the use of that antifibrotic drug in combination with antischistosomal drug, praziquantel (PZQ) was more effective in the control of fibrotic processes in schistosomal hepatic fibrosis.
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