Therapeutic effect of alpha lipoic acid combined with praziquantel on liver fibrosis induced by Schistosoma mansoni challenged mice (original) (raw)
Related papers
The Egyptian Journal of Hospital Medicine, 2009
Background: This study deals with the evaluation of parasitological, histopathological and biochemical effect of Praziquantel (PZQ) and Mirazid (MZ) with or without Selenium-ACE (Se-ACE) on male albino mice infected with S.mansoni and trying to evaluate the antioxidant effect of Se-ACE and its role in reducing the severity of the infection. Results: The obtained results indicated that treatment with PZQ produced more reduction in worm burden and ova count/gm liver than MZ compared to the infected control group. PZQ showed the highest reduction in liver granuloma number and diameter when compared to MZ group while both drugs showed a significant effect in restoration of the liver transaminases and protein fractions towards their normal levels indicating the safety of both drugs as anti S. mansoni chemotherapeutics, Se-ACE showed a high efficacy as a co-treatment, potentiating the effect of PZQ and MZ in reducing the worm burden, ova count/gm liver, number and diameter of liver granuloma and restoration of liver transaminases and protein fractions to their normal levels during treatment of S. mansoni infection. Conclusion: the rank order of potency in protection against liver cell damage was PZQ 500 mg/kg > MZ 600 mg/kg where Se-ACE showed a couraging criterion as a co-treatment potentiating the effect of the antischistosomal medications through its anti-oxidant activity.
This study assessed the effectiveness of an aqueous extract of Moringa Oleifera Lam. leaves (MOL) alone or in combination with praziquantel (PZQ) drug targeting-infected mice with Schistosoma mansoni-induced liver and spleen damage. Mice were divided into eight groups control mice group treated orally with saline. PZQ group: non-infected mice treated orally with 300 mg/kg bwt PZQ three consecutive days. MOL group: non-infected mice treated orally with 150 mg/kg bwt MOL extract for 15 days. PZQ/ MOL group: non-infected mice treated orally with 300 mg/kg bwt PZQ for three consecutive days and 150 mg/kg bwt MOL extract for 15 days. IF group: infected mice with 100 cercariae/ mouse of the Egyptian strain of S. mansoni. IF/PZQ group infected mice with S. mansoni cercariae and treated orally with 300 mg/kg bwt PZQ for three consecutive days. IF/MOL group: infected mice with S. mansoni cercariae treated orally with 150 mg/kg bwt MOL extract for 15 days. IF/PZQ +MOL group: infected mice with S. mansoni cercariae treated orally with 300 mg/kg bwt PZQ for three consecutive days and 150 mg/kg bwt MOL extract for 15 days. Blood, liver, spleen, worm, and eggs were collected at the end of the experimental period. Treatment of infected mice with MOL and PZQ together significantly reduced the number of ova/g tissue and eliminated the parasites. In addition, the liver and spleen of infected mice showed less histopathological alteration and immunohistochemical expression of nuclear factor kappa β (NF-Kβ). We can conclude that MOL extract combined with PZ has a curative effect on S. mansoni infection and helped to lessen its pathological effects.
Experimental Parasitology, 2008
Schistosoma mansoni (S. mansoni) eggs trapped in the host liver elicit a chain of oxidative processes that may be, at least in part, responsible for the pathology and progression of fibrosis associated with schistosomal hepatitis. This study was designed to assess the protective effect of the antioxidant coenzyme-Q10 (Co-Q10) against experimental S. mansoni-induced oxidative stress in the liver, and its potential role as an adjuvant to praziquantel (PZQ) therapy. The oxidative stress and overall liver function were improved under Co-Q10 therapy as evidenced by significant reduction in oxidative stress markers and preservation of antioxidant factors. Liver fibrosis was also reduced with a positive impact on liver function. Moreover, addition of Co-Q10 to PZQ therapy caused: significant reduction of liver egg load, significant improvement of the redox status, and lastly decreased liver fibrosis.
Journal of Applied Pharmaceutical Science
Background: Chemotherapy with praziquantel is the cornerstone of schistosomiasis control, but an oxidative/nitrative stress may occur after a short-term treatment and participate in side effects. It was recommended that the drug must be re-evaluated because of its potential carcinogenicity and genotoxicity. Therefore, the aim of this study is to evaluate the antioxidant and genotoxic effects of the novel antischistosomal enaminone derivative of 4–hydroxyquinoline, BDHQ, alone or combined with PZQ in hepatic tissues of uninfected and Schistosoma mansoni challenged mice. Methodology/Principal Findings: Eight groups of mice were used in this study. The first group represented the uninfected untreated control. The second group was infected with 50±10 S. mansoni cercariae. Groups (3-5) were also infected and treated with PZQ (500 mg/kg), BDHQ (600 mg/kg) and PZQ (250 mg/kg) combined with BDHQ (300 mg/kg) for 2 consecutive days 6 weeks post-infection (PI), respectively. Groups (6-8) inclu...
Mohammad Aziza, Amer Ragheb Adel Azizb,* a Department of Parasitology, Medical Research Institute ,Alexandria University, Alexandria, Egypt. Safepharma Research Laboratory, Alexandria, Egypt. b Department of Parasitology, Faculty of veterinary medicine, Souhag University, Souhag; Egypt, 82524., 2017
Schistosoma mansoni worms inhabit the portal triad affecting blood elements. Therefore, the current study aimed to compare ameliorative effects of Commiphora molmol extract (Mirazid, MZD) and praziquantel (PZQ) on some biochemical parameters in S. mansoni-infected mice. Accordingly, Swiss albino mice (n=72) were used and were divided into 4 equal groups; 18 mice each. Group (1) was uninfected non-treated control. Mice in infected groups administered 100 S. mansoni cercariae/mouse. Group (2) contained infected non-treated mice. Group (3) was infected and treated with MZD at a dose of 500 mg/kg for 5 successive days. Group (4) was infected and treated with PZQ in a dose of 500 mg/kg for 2 successive days. Treatment started 7 weeks post infection (WPT) by the oral route. Blood samples were collected at the 1st, 2nd and 4th weeks post treatment for liver functions (ALT, AST and ALP), kidney functions tests (blood urea and serum creatinine) and cholinergic function (serum cholinesterase level). PZQ ameliorated activities of serum enzymes; alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase more than MZD compared to infected untreated group. PZQ significantly decreased ALT at 1, 2 and 4 WPT as well as AST and ALP activity at 2 and 4 WPT whereas, MZD resulted in significant reduction in ALT activity at the 1st, 2nd and 4th WPT. AST and ALP activities appeared at the 2nd and 4th WPT. PZQ caused progressive significant reduction in elevated levels of urea and creatinine at the 1st, 2nd and 4th WPT, respectively that produced by MZD. PZQ and MZD induced a significant elevation in the level of AChE. Such effect was early detected MZD, and it was showed at the 2nd and 4th WPT for PZQ. It was concluded that PZQ and MZD were safe drugs with no adverse biochemical effects on S. mansoni-infected treated mice with potential action done by PZQ rather than MZD.
Introduction: In this study we focused on novel antischistosomal toll-like receptor (TLR) agonists which induced immune cells to produce a plethora of inflammatory cytokines against shistosoma mansoni infection. We used in this study two importants agonists TLR3L (polyinosinicsalsidylic acid; poly I:C) andTLR2L zymosan. We divided this study into 2 experiments 1. The adjuvant effect of polyI:C orzymosan with soluble worm antigen (SWAP antigen) and we divided it into negative control group, positive control group,vaccinated group with SWAP antigen, vaccinated group with SWAP antigen plus poly I:C,vaccinated group with SWAP antigen pluszymosan 2. Antischistosomal effect of poly I:C orzymosan and we divided it intonegative control group, two positive control groups, treated groups with poly(I:C) on day 25 or day 35 after infection, treated groups with zymosan on day 25 and day 35 after infection. Antischistosomal effect of poly I:C or zymosan was evaluated by measuring serum biochemical parameters as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma glutamyl transferase, albumin and total protein. We measured also oxidative stress parameters such as glutathione S. transferase, catalase, total antioxidant capacity, total thiol and malondialdehyde in liver homogenate, in addition to the histopathological examinations of all mice liver tissue with measuring granuloma sizes of all infected and treated groups and finally we measured the parasitological parameters as worm burden, liver and intestine eggs count.
Acta Parasitologica, 2012
Schistosomiasis is caused by Schistosoma mansoni and is a public health problem in Brazil. The typical granulomatous lesion is associated with the increase in the oxidative damage by generation of free radicals. The aim of this work was to correlate some oxidative stress markers with the worm burden on carriers of schistosomiasis (n = 30) in the acute phase in comparison to healthy subjects (n = 30). The pro-oxidant parameter used was the colorimetric quantification of reactive substances to thiobarbituric acid, while the antioxidant markers used were blood content of reduced glutathione and determination of the activity of catalase. The worm burden was assessed by Kato-Katz method. The results pointed out that initially there was no difference in the catalase activity. However, there was a positive correlation between the increase in parasitic load and intensity of lipid peroxidation, and decrease in the content of reduced glutathione. Additionally, only the aspartate aminotransfer...
Journal of Traditional and Complementary Medicine, 2018
The roots of Ozoroa pulcherrima Schweinf are used in traditional medicine to treat intestinal helminthiasis. The aim of this study was to assess the effect of Ozoroa pulcherrima roots methanolic extract (OPME) on liver injury induced by Schistosoma mansoni in mice. A preliminary phytochemical study of OPME was conducted. OPME was given daily and orally to S. mansoni-infected mice at 100, 200 or 400 mg/kg for 28 days, starting from the 36th day post-infection. Praziquantel was used as reference drug. Non-infected and infected-untreated mice served as controls. Worm burden and egg output, transaminases, total bilirubin, alkaline phosphatase and total protein; as well as malondialdehyde, catalase and reduced glutathione were evaluated. In OPME, total phenolic was 79.61 ± 0.25 mg gallic acid equivalent/g, while total flavonoid was 7.98 ± 0.04 mg rutin equivalent/g. Treatment of S. mansoniinfected mice with OPME produced significant reduction of worm burden and ova count in the faeces, liver and intestine. Significant reduction of alanine aminotransferase activity (p < 0.001) as well as significant increase of total protein content (p < 0.001) was recorded after OPME treatment at all doses. Total bilirubin level was also reduced (p < 0.01). Administration of OPME at all doses corrected the high malondialdehyde level (p < 0.001) induced by the infection. At 200 mg/kg, catalase activity and reduced glutathione concentration were significantly increased (p < 0.001). OPME at 200 mg/kg showed moderate schistosomicidal effect, but was effective as the standard drug praziquantel in restoring the liver function after S. mansoni infection.
Parasites & Vectors, 2019
Background: Treatment of schistosomiasis has relied on the anthelmintic drug praziquantel (PZQ) for more than a generation. Despite its celebrated performance for treatment and control of schistosomiasis and other platyhelminth infections, praziquantel has some shortcomings and the inability of this drug to counteract disease sequelae prompts the need for novel therapeutic strategies. Methods: Using a host-parasite model involving Biomphalaria glabrata and Schistosoma mansoni we established mechanical transformation of S. mansoni cercariae into newly transformed schistosomula (NTS) and characterized optimal culture conditions. Thereafter, we investigated the antischistosomal activity and ability of the antioxidants N-acetylcysteine (NAC) and resveratrol (RESV) to augment the performance of praziquantel and/or artesunate (AS) against larval stages of the parasite. Drug effects were evaluated by using an automated microscopical system to study live and fixed parasites and by transmission electron microscopy (TEM). Results: Transformation rates of cercariae to schistosomula reached ~ 70% when the manipulation process was optimized. Several culture media were tested, with M199 supplemented with HEPES found to be suitable for S. mansoni NTS. Among the antioxidants studied, RESV alone or combined with anthelminthic drugs achieved better results rather N-acetylcysteine (NAC). TEM observations demonstrated that the combination of AS + RESV induced severe, extensive alterations to the tegument and subtegument of NTS when compared to the constituent compounds alone. Two anthelmintic-antioxidant combinations, praziquantel-resveratrol [combination index (CI) = 0.74] and artesunate-resveratrol (CI = 0.34) displayed moderate and strong synergy, respectively. Conclusions: The use of viability markers including staining with propidium iodide increased the accuracy of drug screening assays against S. mansoni NTS. The synergies observed might be the consequence of increased action by RESV on targets of AS and PZQ and/or they may act through concomitantly on discrete targets to enhance overall antischistosomal action. Combinations of active agents, preferably with discrete modes of action including activity against developmental stages and/or the potential to ameliorate infection-associated pathology, might be pursued in order to identify novel therapeutic interventions.
International Journal of Infectious Diseases, 2010
The main problem in schistosomal hepatic morbidity is fibrosis and extensive scarring induced by living eggs. In this study, we tried to study the effect of treatment using antihelminthic drug (PZQ) and/or antifibrotic drugs (PTX and silymarin) in combination with immunization. The parasitological parameters, the dynamics of serum-specific immunoglobulins and splenic cytokines associated with changes in granuloma diameter were assessed. Naïve mice were immunized intravenously with 10 ug of SEA in three doses at 2 days intervals 6 weeks before infection. Animals were infected by tail immersion with 100 cercariae and divided into several groups. Three groups were treated with PZQ, PTX or silymarin administered alone. Another two groups were treated with PZQ combined with PTX or silymarin. All treated animals and respective controls were sacrificed 12 weeks post infection. Immunization did not affect worm reduction , but slight decrease in granuloma diameter, increase in immunoglobulins and cytokines was observed. Reduction in worm burden was associated with reduction in ova count and changes in oogram pattern which were mainly due to PZQ treatment. Increasing reduction in granuloma diameter, elevation of immunogloulins and cytokines levels were observed in the groups treated with PZQ alone or cmbined with PTX or silymarin. In conclusion, in this study, treatment with PZQ complemented with immunization resulted in significant reduction of parasitological parameters and rise of specific Igs. Addition of antifibrotic drugs PTX or silymarin to PZQ, potentiated an antipathology effect which minimized and ameliorated liver fibrosis by inhibition of HSC activation and accentuation of the effect of suppressor Treg cells.