Effect of Combined Chemotherapy and Anti-inflammatory Drugs on Murine Schistosomiasis

Mahmoud, Madiha R.; Zoheiry, Mona; Nosseir, M. H.

doi:10.1055/s-0031-1299893

Cited by 7 publications

(12 citation statements)

References 22 publications

(27 reference statements)

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“…This could be attributed to the absence of any toxic effect exerted by TELM on either the eggs trapped in the tissues or the intravascular worms. On the other hand, the reductions in the hepatomesenteric worm load as well as viable egg (mature and immature) percentages observed with PZQ, either alone or combined with TELM, are in agreement with previous studies in which PZQ was used, either alone [33] or in combination with a proposed enhancer such as Nigella sativa oil [34], or dietary zinc supplement [35]. …”

Section: Discussionsupporting

confidence: 91%

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

et al. 2013

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BackgroundHepatic schistosomiasis is considered to be one of the most prevalent forms of chronic liver disease in the world due to its complication of liver fibrosis. The demonstration of the pro-fibrogenic role of angiotensin (Ang) II in chronic liver disease brought up the idea that anti-Ang II agents may be effective in improving hepatic fibrosis by either blocking Ang II type 1 (AT1) receptors or inhibiting the angiotensin converting enzyme. Peroxisome proliferator-activated receptors gamma (PPARγ) activation has been also shown to inhibit hepatic stellate cell activation and progression of fibrosis. The present study has aimed at testing the anti-fibrogenic effects of telmisartan; an AT1 receptor blocker and a PPARγ partial agonist, alone or combined with praziquantel (PZQ) on Schistosoma mansoni-induced liver fibrosis in mice.MethodsTo achieve the aim of the study, two sets of experiments were performed in which telmisartan was initiated at the 5th (set 1) and the 10th (set 2) weeks post infection to assess drug efficacy in both acute and chronic stages of liver fibrosis, respectively. Schistosoma mansoni-infected mice were randomly divided into the following four groups: infected-control (I), telmisartan-treated (II), PZQ-treated (III), and telmisartan+PZQ-treated (IV). In addition, a normal non-infected group was used for comparison. Parasitological (hepatomesenteric worm load and oogram pattern), histopathological, morphometric, immunohistochemical (hepatic expressions of matrix metalloproteinase-2; MMP-2 and tissue inhibitor of metalloproteinase-2; TIMP-2), and biochemical (serum transforming growth factor beta 1; TGF-β1 and liver function tests) studies were performed.ResultsTelmisartan failed to improve the parasitological parameters, while it significantly (P<0.05) decreased the mean granuloma diameter, area of fibrosis, and serum TGF-β1. Additionally, telmisartan increased MMP-2 and decreased TIMP-2 hepatic expression. Combined treatment failed to show any additive properties, yet it did not affect the anti-schistosomal activity of PZQ.ConclusionsThese results suggest potential anti-fibrotic effects of telmisartan, an AT1 receptor blocker and a PPARγ partial agonist, in acute and chronic stages of Schistosoma mansoni–induced liver fibrosis in mice.

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Section: Discussionsupporting

confidence: 91%

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

et al. 2013

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“…Moreover, a significant reduction in granuloma diameter was observed in KTZ+QN-treated group vs QN-treated group. Such reductions in granuloma diameter may be attributed to elimination of adult worms by the treatment regimens leading to sustained diminution of egg-induced immunopathology [53] and consequent stopping of further egg deposition [24,54]. The combined treatment regimen of KTZ+QN after S. mansoni infection had an added merit of maximal amelioration of histopathological changes where the liver sections of this group showed remarkably better cellular architecture upon comparing with the S. mansoni -infected untreated and QN-treated groups.…”

Section: Discussionmentioning

confidence: 99%

Effect of Ketoconazole, a Cytochrome P450 Inhibitor, on the Efficacy of Quinine and Halofantrine against Schistosoma mansoni in Mice

et al. 2013

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The fear that schistosomes will become resistant to praziquantel (PZQ) motivates the search for alternatives to treat schistosomiasis. The antimalarials quinine (QN) and halofantrine (HF) possess moderate antischistosomal properties. The major metabolic pathway of QN and HF is through cytochrome P450 (CYP) 3A4. Accordingly, this study investigates the effects of CYP3A4 inhibitor, ketoconazole (KTZ), on the antischistosomal potential of these quinolines against Schistosoma mansoni infection by evaluating parasitological, histopathological, and biochemical parameters. Mice were classified into 7 groups: uninfected untreated (I), infected untreated (II), infected treated orally with PZQ (1,000 mg/kg) (III), QN (400 mg/kg) (IV), KTZ (10 mg/kg)+QN as group IV (V), HF (400 mg/kg) (VI), and KTZ (as group V)+HF (as group VI) (VII). KTZ plus QN or HF produced more inhibition (P<0.05) in hepatic CYP450 (85.7% and 83.8%) and CYT b5 (75.5% and 73.5%) activities, respectively, than in groups treated with QN or HF alone. This was accompanied with more reduction in female (89.0% and 79.3%), total worms (81.4% and 70.3%), and eggs burden (hepatic; 83.8%, 66.0% and intestinal; 68%, 64.5%), respectively, and encountering the granulomatous reaction to parasite eggs trapped in the liver. QN and HF significantly (P<0.05) elevated malondialdehyde levels when used alone or with KTZ. Meanwhile, KTZ plus QN or HF restored serum levels of ALT, albumin, and reduced hepatic glutathione (KTZ+HF) to their control values. KTZ enhanced the therapeutic antischistosomal potential of QN and HF over each drug alone. Moreover, the effect of KTZ+QN was more evident than KTZ+HF.

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“…Drug testing to treat schistosome infection has very largely involved the use of rodents as host animals (43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55). Other approaches include testing novel drugs for their ability to inhibit the function of recombinant schistosome proteins or testing drug treatments on schistosomula or adult parasites ex vivo.…”

Section: Using In Vivo Imaging To Assess Antischistosome Interventionsmentioning

confidence: 99%

“…Once infection is established, a test drug is then administered in several formulations, doses, and/or routes. To determine the effectiveness of each treatment, the animals are then killed at specified time points posttreatment and their worm burdens are assessed by perfusion (43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55).…”

Section: Using In Vivo Imaging To Assess Antischistosome Interventionsmentioning

confidence: 99%

Imaging schistosomes in vivo

Krautz‐Peterson

Ndegwa

Vasquez³

et al. 2009

FASEB j.

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Schistosomes are intravascular, parasitic helminths that cause a chronic, often debilitating disease afflicting over 200 million people in over 70 countries. Here we describe novel imaging methods that, for the first time, permit visualization of live schistosomes within their living hosts. The technology centers on fluorescent agent uptake and activation in the parasite's gut, and subsequent detection and signal quantitation using fluorescence molecular tomography (FMT). There is a strong positive correlation between the signal detected and parasite number. Schistosoma mansoni parasites of both sexes recovered from infected experimental animals exhibit vivid fluorescence throughout their intestines. Likewise, the remaining important human schistosome parasites, S. japonicum and S. hematobium, also exhibit gut fluorescence when recovered from infected animals. Imaging has been used to efficiently document the decline in parasite numbers in infected mice treated with the antischistosome drug praziquantel. This technology will provide a unique opportunity both to help rapidly identify much-needed, novel antischistosome therapies and to gain direct visual insight into the intravascular lives of the major schistosome parasites of humans.

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Effect of Combined Chemotherapy and Anti-inflammatory Drugs on Murine Schistosomiasis

Cited by 7 publications

References 22 publications

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

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

Effect of Ketoconazole, a Cytochrome P450 Inhibitor, on the Efficacy of Quinine and Halofantrine against Schistosoma mansoni in Mice

Imaging schistosomes in vivo

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