The potential role of mefloquine against Schistosoma mansoni infection by prohibition of hepatic oxidative stress in mice

Fahmy, Sohair R.; Rabia, Ibrahim; Mansour, E.M.

doi:10.1016/j.jobaz.2014.09.002

Cited by 17 publications

(12 citation statements)

References 38 publications

(43 reference statements)

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“…Determination of liver enzyme function, reflected by serum AST and ALT levels, is commonly used to assess the liver damage caused by schistosomal infection [39]. These enzymes are important markers of hepatocellular damage as affirmed by Al-Olayan et al [32].…”

Section: Discussionmentioning

confidence: 99%

Ceratonia siliqua pod extract ameliorates Schistosoma mansoni-induced liver fibrosis and oxidative stress

Al-Olayan

El‐Khadragy

Alajmi

et al. 2016

BMC Complement Altern Med

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BackgroundSchistosomiasis is a prevalent parasitic disease found predominantly in tropical and sub-tropical areas of the developing world, with the second highest socioeconomic and public health burden despite strenuous control efforts. In the present study, we aimed to investigate the ameliorative effects of Ceratonia siliqua pod extract (CPE) on liver fibrosis and oxidative stress in mice infected with Schistosoma mansoni.MethodsThe schistosomal hepatopathologic mouse model was established by tail immersion with schistosomal cercaria. The extract was given daily for 10 days beginning 42 days post-infection. Liver samples were obtained from mice sacrificed 9 weeks after infection. Liver histopathological changes were observed with hematoxylin-eosin and Masson trichrome staining.ResultsTypical schistosomal hepatopathologic changes were induced in the untreated mice. However, the oral administration of CPE was effective in reducing worm number and the egg load in the liver. This treatment also decreased granuloma size and collagen deposition by inhibiting tissue inhibitor of metalloproteinases-2 (TIMP-2) expression. Schistosomal infection induced oxidative stress by increasing lipid peroxidation (LPO) and nitrite/nitrate (nitric oxide; NO) production along with concomitant decreases in glutathione (GSH) and various antioxidant enzymes, including superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. However, treatment of mice with CPE at 300 or 600 mg/kg inhibited LPO and NO production, increased GSH content, and restored the activities of the antioxidant enzymes compared with untreated infected mice. Furthermore, treatment with CPE inhibited apoptosis, as indicated by the reduced Bax expression in hepatic tissue.ConclusionThese data indicated that extracts from Ceratonia siliqua pods may play an important role in combating schistosomal hepatopathology and may inhibit granuloma formation and liver fibrosis through down-regulation of TIMP-2 expression.Electronic supplementary materialThe online version of this article (doi:10.1186/s12906-016-1389-1) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Ceratonia siliqua pod extract ameliorates Schistosoma mansoni-induced liver fibrosis and oxidative stress

Al-Olayan

El‐Khadragy

Alajmi

et al. 2016

BMC Complement Altern Med

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“…Mahmoud and Elbessoumy (2013) concluded that schistosomiasis induced a significant decrease in GSH level in mice liver, thus serving to decrease the hepatic antioxidant capacity and generating lipid peroxides that may in turn play a central role in the pathology associated with schistosomiasis (Fahmy et al, 2014). Moreover, Gharib et al (1999) attributed the decreased GSH level to the increased cytotoxicity with H 2 O 2 which is produced as a result of inhibition of glutathione reductase that keeps GSH in its reduced form.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of nanoselenium and nanogold activities against murine intestinal schistosomiasis

Dkhil

Khalil

Diab

et al. 2019

Saudi Journal of Biological Sciences

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Nanomedicine is one of the most important methods used to treat human diseases including parasitic diseases. Schistosomiasis is a major parasitic disease that affects human health in tropical regions. Whilst Praziquantel is the main classic antischistosomal drug, new drugs are required due to the poor effect of the drug on the parasite juveniles and immature worms, and the emergence of drug resistant strains of Schistosoma. The present study aimed to examine the curative roles of both gold and selenium nanoparticles on jejunal tissues of mice infected with Schistosoma mansoni. Transmission electron microscopy was used for characterization of nanoparticles. Gold nanoparticles of 1 mg/kg mice body weight and selenium nanoparticles 0.5 mg/kg body weight were inoculated separately into mice infected with S. mansoni. The parasite induced a significant decrease in glutathione levels; however, the levels of nitric oxide and malondialdehyde were significantly increased. Additionally, the parasite introduced deteriorations in histological architecture of the jejunal tissue. Treatment of mice with metal nanoparticles reduced the levels of body weight changes, oxidative stress and histological impairment in the jejunal tissue significantly. Therefore, our results revealed the protective role of both selenium and gold nanoparticles against jejunal injury in mice infected with S. mansoni.

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“…Chemical burn causes the formation of free radicals, which in turn provokes angiogenesis. Mefloquine, which is an antioxidant and free radical scavenger, protects the endothelium from oxidative stress independent of anti-angiogenic activity [22]. So, these could be the apparent mechanisms of mefloquine in the prevention of proliferation and thus the associated angiogenesis.…”

Section: Discussionmentioning

confidence: 99%

Anti-angiogenic activity of chloride and potassium channel modulators: repurposing ion channel modulators

et al. 2020

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Background: Excessive angiogenesis can be the root cause of many pathological conditions. Various types of ion channels are found on the endothelial cells. These ion channels play a vital role in the multi-stepped process of angiogenesis. The study aims to investigate the anti-angiogenic effects of specific ion channel modulators mefloquine (volume-regulated chloride channel blocker), lubiprostone (ClC-2 channel agonist), and 4-aminopyridine (voltage-gated potassium channel blocker). Results: The anti-angiogenic activity of ion channel modulators was screened by measuring its effects on the area of neovascularization and histopathological studies by in vivo (corneal neovascularization) method and by in vitro assays, endothelial cell proliferation assay, cell migration assay, and matrigel cord-like morphogenesis assay. The test and standard drug (bevacizumab) groups were compared with the control group using one-way ANOVA, followed by post hoc test, and Dunnett's test to compare the mean of all the groups with the control mean. The results revealed that mefloquine at the dose of 0.6% w/v and 1.0% w/v, lubiprostone at the dose of 0.5% w/v and 1.0% w/ v, and 4-aminopyridine at the dose of 2% w/v and 4% w/v showed significant anti-angiogenic property. In the studies on human umbilical vein endothelial cells, the test drugs (100 nM) showed significant inhibition of proliferation, migration, and decrease in network length of cord-like tubes. Conclusion: The scientific findings indicate that the test drugs have potent anti-angiogenic activity by inhibiting the cell proliferation, inhibiting the cell volume increase, arresting the cell cycle progression and by causing membrane hyperpolarization. The potent anti-angiogenic drugs obtained by repurposing these ion channel modulators, in the further studies, will be able to treat the diseases due to excess angiogenesis from the root cause.

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The potential role of mefloquine against Schistosoma mansoni infection by prohibition of hepatic oxidative stress in mice

Cited by 17 publications

References 38 publications

Ceratonia siliqua pod extract ameliorates Schistosoma mansoni-induced liver fibrosis and oxidative stress

Ceratonia siliqua pod extract ameliorates Schistosoma mansoni-induced liver fibrosis and oxidative stress

Evaluation of nanoselenium and nanogold activities against murine intestinal schistosomiasis

Anti-angiogenic activity of chloride and potassium channel modulators: repurposing ion channel modulators

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