Efficacy of Pentoxifylline as an Antifibrotic Drug in Experimental Murine Schistosomal Hepatic Fibrosis

Document Type : Original Article

Authors

1 Department of Parasitology, Faculty of Medicine-Tanta University

2 Department of Pharmacology, Faculty of Medicine-Tanta University

3 Department of Tropical Medicine, Faculty of Medicine-Tanta University

4 Department of Medical Biochemistry, Faculty of Medicine-Tanta University

Abstract

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, non-treated 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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