Pharmacodynamics of pentoxifylline and/or praziquantel in murine schistosomiasis mansoni

Abstract

Pentoxifylline (PTX) was proved to exert both anti-inflammatory and anti-fibrotic effects, and was used therapeutically in this experimental model to investigate its role alone or with praziquantel (PZQ) in Schistosoma mansoni-infected mice, and to explore its impact on the tissue expression of transforming growth factor-beta1 (TGF-beta1). S. mansoni-infected mice were divided into seven groups: Control untreated (I), treated with curative dose of PZQ, 500 mg/kg/day for 2 consecutive days (II), or subcurative dose, 100 mg/kg/day for 2 consecutive days (III), treated with PTX (10 mg/kg/day for 5 days/wk) alone for 4 weeks (IV) or in addition to subcurative dose of PZQ (V), and treated with PTX alone for 8 weeks (VI) or in addition to subcurative dose of PZQ (VII). All animals were killed 10 weeks post infection. Parasitological assessment of worm burden, tissue egg load and oogram pattern was carried out. The degree of granulomatous fibrosis and eosinophilic cell population was quantified in Sirius-red-stained sections and tissue transforming growth factor beta-1 expression was estimated immunohistochemically. Serum ALAT and GGT, as well as hepatic content of reduced GSH, were measured. The results revealed the highest percent of worm reduction and dead ova in groups (II) and (VII) accompanied by significant diminution in granulomatous parameters, collagen content and TGF-beta1 tissue expression. Moreover, treatments with PTX and/or PZQ ameliorated the liver functions. In conclusion, prolonged treatment with PTX has a potent anti-fibrogenic role especially when used in the early stages of infection, with limited toxic effects on schistosome worms and eggs. Thus, PTX can be used as an adjuvant therapeutic tool with anti-helminthic drugs in the treatment of human schistosomiasis.

Cytokine patterns in experimental schistosomiasis mansoni infected mice treated with silymarin

“…In this study, the histopathological examination of the livers in group treated with PZQ showed a reduction in the diameter of livers eggs granuloma at all periods of sacrification compared with infected untreated group in agreement with El-Lakkany and Nosseir (2007). PZQ exert significant regulatory effects on cell immune responses which reduces CD4…”

Telmisartan, an AT1 receptor blocker and a PPAR gamma activator, alleviates liver fibrosis induced experimentally by Schistosoma mansoni infection

“…mansoni eggs, TGF-β1 is produced and may modulate inflammation and hence regulate fibrogenesis [43,44]. In the current study, TELM caused significant reductions in serum TGF-β1 levels in both sets.…”

“…The reduction in TGF-β1 levels elicited by PZQ is consistent with the studies of Singh et al . [43]; El-Lakkany & Nosseir [44], and El-Lakkany et al . [45] that revealed a marked drop (amounting to 70% in the first study) in the TGF-β1 expression caused by PZQ in S .…”

Effects of pentoxifylline duringSchistosoma mansoniinfection in Swiss mice: an analysis of worm burden, fecundity and liver histopathology

“…However, the immunomodulatory activity of PTX has been related to inhibition of pro-inflammatory cytokines besides TNF-a, such as interleukin-1 (IL-1), IL-12 and IFN-g (Bienvenu et al, 1995;Heyderman et al, 1995;Navarro et al, 1996;Marcinkiewicz et al, 2000), as well as IL-10, the anti-inflammatory cytokine that enhances Th1-type cell proliferation and reduces that of the Th2 type (Navarro et al, 1996). Reduction in TGF-b1 and collagen in experimental schistosomiasis mansoni has been reported (El-Lakkany & Nosseir, 2007), but further investigations are necessary. Reduction in TGF-b1 and collagen in experimental schistosomiasis mansoni has been reported (El-Lakkany & Nosseir, 2007), but further investigations are necessary.…”