Inhibition of malate dehydrogenase enzymes by benzimidazole anthelmintics

Tejada, P.; Sánchez‐Moreno, Manuel; Monteoliva, M.; Gomez-Banqueri, H.

doi:10.1016/0304-4017(87)90048-3

Cited by 29 publications

(13 citation statements)

References 18 publications

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“…This inhibition indicates an overall inhibition of the glycolytic pathway, with a consequent decline in the energy reserves of the helminths. Drug-induced inhibition of MDH activity was observed in F. hepatica, F. gigantica, F. buski and P. explanatum [52,53] and several other helminth parasites [47,[54][55][56]. Similar inhibitory effect of aqueous extracts of A. sativum on the cMDH and mMDH activity of H. contortus was reported by Lakshmi and Veerakumari [49].…”

Section: Resultssupporting

confidence: 60%

Effect of Allium sativum on the Carbohydrate Metabolism of Haemonchus contortus

2015

IJSR

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Gastrointestinal (GI) nematode infections in small ruminants are widely prevalent in Indian sub continent and leads to heavy economic losses to meat and wool industries worldwide, among which a nematode, Haemonchus contortus account for more losses in livestock. In the present investigation, the effect of Allium sativum ethanol extract (AsEE) on the enzymes of carbohydrate metabolism viz. pyruvate kinase (PK), phosphoenolpyruvate carboxykinase (PEPCK), lactate dehydrogenase (LDH), malate dehydrogenase (MDH), fumarate reductase (FR) and succinate dehydrogenase (SDH) of Hamonchus contortus was studied in vitro. The parasites were incubated in five different sub-lethal concentrations of AsEE viz. 0.005, 0.01, 0.05, 0.1 and 0.5 mg/ml for 2, 4 and 8h. The activity of all the enzymes of carbohydrate metabolism was assayed using standard procedures. The enzyme activity was expressed in terms of protein. The data obtained were analyzed statistically. AsEE significantly inhibited the enzymes of carbohydrate metabolism and the percentage of inhibition was dose and time dependent. Impairment of carbohydrate metabolism in parasitic helminths may be disastrous since they depend almost entirely on it for their energy supply. Consequently, the energy deprived parasite unable to sustain them in situ may be expelled from the host, Hence, AsEE can be used as anthelmintic drug to control haemonchosis.

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Section: Resultssupporting

confidence: 60%

Effect of Allium sativum on the Carbohydrate Metabolism of Haemonchus contortus

2015

IJSR

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“…To determine whether MDH2 inhibition was responsible for the cardioprotective effect of VIS, structurally diverse MDH2 inhibitors were selected from the published literature and tested for their ability to protect the heart from doxorubicin (19, 20). In cultured HL1 cells, mebendazole, thyroxine (T4), and iodine all increased cardiomyocyte viability compared to doxorubicin treatment alone (Fig 4D).…”

Section: Resultsmentioning

confidence: 99%

Visnagin protects against doxorubicin-induced cardiomyopathy through modulation of mitochondrial malate dehydrogenase

et al. 2014

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Doxorubicin is a highly effective anti-cancer chemotherapy agent, but its usage is limited by its cardiotoxicity. To develop a drug that prevents the cardiac toxicity of doxorubicin while preserving its anti-tumor potency, we established a doxorubicin-induced cardiomyopathy model in zebrafish that recapitulated the cardiomyocyte apoptosis and contractility decline observed in patients. Using this model, we screened 3000 compounds and discovered that visnagin (VIS) and diphenylurea (DPU) rescue cardiac performance and circulatory defects caused by doxorubicin treatment in zebrafish. VIS and DPU reduced doxorubicin-induced apoptosis in cultured cardiomyocytes and in vivo in zebrafish and mouse hearts. Furthermore, VIS treatment improved cardiac contractility in doxorubicin-treated mice. Importantly, VIS and DPU caused no reduction in the chemotherapeutic efficacy of doxorubicin in several cultured tumor lines or in zebrafish and mouse xenograft models. Using affinity chromatography, we discovered that VIS binds to mitochondrial malate dehydrogenase (MDH2), one of the key enzymes in the tricarboxylic acid cycle. As with VIS, treatment with the MDH2 inhibitors mebendazole, thyroxine, and iodine prevented doxorubicin cardiotoxicity, as did treatment with malate itself, suggesting that modulation of MDH2 activity is responsible for VIS’s cardioprotective effects. Taken together, this study identified VIS and DPU as potent cardioprotective compounds and implicates MDH2 as a previously undescribed, druggable target for doxorubicin-induced cardiomyopathy.

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“…SaEE significantly inhibited the cytoplasmic MDH (cMDH) and mitochondrial MDH (mMDH) catalysing both the oxidation and reduction reactions in C. cotylophorum (Table 1c & 1d). Inhibition of MDH activity of Ascaris suum, F. hepatica and Moniezia expansa by mebendazole, albendazole and parbendazole was reported by Tejada et al [46]. Also, Oztop et al [47] reported the alteration of MDH and LDH activities of Trichuris saginata by albendazole and niclosamide.…”

Section: Resultsmentioning

confidence: 89%

In Vitro Studies on the Effect of Ethanol Extract of Syzygium Aromaticum on the Carbohydrate Metabolism of Cotylophoron Cotylophorum

Dhanraj¹,

Veerakumari²

2015

IJAVST

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Paramphistomosis is one of the major pathogenic diseases in domestic animals and responsible for heavy economic loss in terms of reduced milk, meat and wool production. Cotylophoron cotylophorum is more prevalent in Tamilnadu. In the present investigation, the effect of Syzygium aromaticum ethanol extract on the enzymes of carbohydrate metabolism viz. pyruvate kinase, phosphoenolpyruvate carboxykinase, lactate dehydrogenase, malate dehydrogenase, fumarate reductase and succinate dehydrogenase of Cotylophoron cotylophorum was studied in vitro. The parasites were incubated in five different sub-lethal concentrations of ethanol extract of Syzygium aromaticum viz. 0.005, 0.01, 0.05, 0.1 and 0.5mg/ml for 2, 4 and 8 h. The activity of the enzymes was assayed using standard procedures. The enzyme activity was expressed in terms of protein. The data obtained were analyzed statistically. Ethanol extract of Syzygium aromaticum significantly inhibited the enzymes of carbohydrate metabolism and the percentage of inhibition was dose and time dependent. Inhibition of these enzymes leads to decreased ATP production which may be fatal to the parasites. The present study validates the anthelmintic property of ethanol extract of Syzygium aromaticum against C. cotylophorum.

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Inhibition of malate dehydrogenase enzymes by benzimidazole anthelmintics

Cited by 29 publications

References 18 publications

Effect of Allium sativum on the Carbohydrate Metabolism of Haemonchus contortus

Effect of Allium sativum on the Carbohydrate Metabolism of Haemonchus contortus

Visnagin protects against doxorubicin-induced cardiomyopathy through modulation of mitochondrial malate dehydrogenase

In Vitro Studies on the Effect of Ethanol Extract of Syzygium Aromaticum on the Carbohydrate Metabolism of Cotylophoron Cotylophorum

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