Antagonistic effect of Vitamin E on the efficacy of artesunate against Plasmodium berghei infection in mice

Awodele, Olufunsho; Emeka, Promise Madu; Akintonwa, A; Aina, OO

doi:10.4314/ajbr.v10i1.48971

Cited by 13 publications

(14 citation statements)

References 12 publications

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“…There are however, recommendations against administration of vitamin C to patients with malaria, to avoid possible impairment of therapeutic action of antimalarial drugs 8 . This is supported by reports of the interference of antiplasmodial action of antimalarial agents in the presence of antioxidants 9 10 .…”

supporting

confidence: 59%

In vitro effects of co-incubation of blood with artemether/lumefantrine & vitamin C on the viscosity & elasticity of blood

2016

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Background & objectives:The antimalarial combination drug artemether/lumefantrine has been shown to be effective against malaria parasite through its haemolytic action. This drug is sometimes co-administered with vitamin C in patients with malaria. Vitamin C is associated with antioxidant properties which would be expected to protect against haemolytic effects of this antimalarial drug. This study was designed to investigate in vitro effects of co-incubation of artemether/lumefantrine with vitamin C on the viscosity and elasticity of blood.Methods:Blood was collected from 12 healthy female volunteers with normal haemoglobin genotype (HbAA). A Bioprofiler was used to measure the viscosity and elasticity of untreated blood samples (control) and samples exposed to artemether/lumefantrine (0.06/0.36 mg/ml) alone and with low or high dose vitamin C (equivalent to adult doses of 100 or 500 mg).Results:Artemether/lumefantrine significantly (P<0.05) reduced viscosity of blood from 4.72 ± 0.38 to 3.78 ± 0.17 mPa.s. Addition of vitamin C (500 mg) further reduced blood viscosity to 2.67 ± 0.05 mPa.s. The elasticity of blood was significantly (P<0.05) reduced from 0.33 ± 0.04 mPa.s to 0.24 ± 0.03 mPa.s by the antimalarial drug, and further reduced to 0.13 ± 0.02 mPa.s in the presence of vitamin C (500 mg).Interpretation & conclusions:Co-incubation of blood with vitamin C and antimalarial combination drug potentiates the haemolytic effects of the latter on reducing blood viscosity and elasticity in vitro. This may possibly have implications in relation to haemolysis in patients receiving vitamin C supplementation with artemether/lumefantrine during malaria therapy.

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confidence: 59%

In vitro effects of co-incubation of blood with artemether/lumefantrine & vitamin C on the viscosity & elasticity of blood

2016

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“…Therefore, one drug molecule can generate only one free radical [ 34 ]. In vitro [ 25 ] and in vivo [ 35 ] studies showed that this anti-malarial effect of artemisinin was reduced by vitamin E treatment. The additive effect of combination treatment as shown in this study might be caused by the lowering effect of probucol on host plasma vitamin E concentration, which prevented the elimination of free radicals generated by DHA.…”

Section: Discussionmentioning

confidence: 99%

Probucol dramatically enhances dihydroartemisinin effect in murine malaria

Kume

Dang-Trinh

Shichiri

et al. 2016

Malar J

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BackgroundArtemisinin-based combination therapy (ACT) has been adopted as national policy for the first-line treatment in large number of malaria-endemic regions. However, artemisinin-resistant parasites have emerged and are spreading, with slow-cleaning parasites being reported in patients treated with ACT. It means that more parasites are exposed to the partner drug alone and the risk of developing resistant parasites against the partner drug is increasing. Therefore, the development of a new method to enhance the effect of artemisinin is required. In this study, the potential effect of probucol as a combination drug of dihydroartemisinin (DHA), an artemisinin derivative, was examined.MethodsC57BL/6 J mice infected with Plasmodium yoelii XL-17 were treated with probucol and/or DHA. The mice were fed with a probucol mixed diet from 2 weeks before infection and through infection period. DHA was injected to mice three to 5 days post infection once a day. In addition, 0.5 % (w/w) probucol was mixed with vitamin E supplemented diet (800 mg/kg) and fed to mice infected with P. yoelii XL-17 to examine the mechanisms of probucol on murine malaria. Furthermore, 8-OHdG, a biomarker of oxidized DNA, was detected in infected red blood cells (iRBC) taken from infected mice by immunofluorescent staining.ResultsWith dose-dependent manner, both probucol and DHA decreased parasitaemia and increased survival rate of mice infected with P. yoelii XL-17. A significantly larger amount of 8-OHdG was detected in iRBC taking from probucol-treated mice than control mice. In addition, a large amount of vitamin E supplementation eliminated the effect of probucol against P. yoelii XL-17 infection and lowered the effect of probucol on host plasma vitamin E concentration. The effective doses for probucol and DHA were 0.5 % and 30 mg/kg, respectively, in each single treatment. While the combination treatment of 0.25 % probucol and 7.5 mg/kg DHA was effective in all mice from P. yoelii XL-17 infection.ConclusionThis study demonstrated that probucol has some impact on malaria by oxidative stress through the induction of host plasma vitamin E deficiency. Moreover, the effective dose of DHA on malaria was decreased by prophylactic treatment of probucol. This finding indicates that probucol might be a candidate for a prophylactic treatment drug to enhance the effect of DHA.

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“…Therefore, one drug molecule can generate only one free radical [77]. Since anti-malarial effect of artemisinin was seen to be reduced by vitamin E treatment both in vitro [73] and in vivo [78], the beneficial effect of the combination treatment of DHA with probucol [61] might be attributed to the lowering of host plasma concentration of vitamin E by probucol, which prevented the elimination of free radicals generated by DHA. Such a strategy might be applicable to other parasites as well in future, such as trypanosoma [20].…”

Section: A Combination Therapy With Dihydroartemisinin and Probucolmentioning

confidence: 99%

Potential of Vitamin E Deficiency, Induced by Inhibition of α-Tocopherol Efflux, in Murine Malaria Infection

Suzuki

Kume

Herbas

2018

IJMS

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Although epidemiological and experimental studies have suggested beneficial effects of vitamin E deficiency on malaria infection, it has not been clinically applicable for the treatment of malaria owing to the significant content of vitamin E in our daily food. However, since α-tocopherol transfer protein (α-TTP) has been shown to be a determinant of vitamin E level in circulation, manipulation of α-tocopherol levels by α-TTP inhibition was considered as a potential therapeutic strategy for malaria. Knockout studies in mice indicated that inhibition of α-TTP confers resistance against malaria infections in murines, accompanied by oxidative stress-induced DNA damage in the parasite, arising from vitamin E deficiency. Combination therapy with chloroquine and α-TTP inhibition significantly improved the survival rates in murines with malaria. Thus, clinical application of α-tocopherol deficiency could be possible, provided that α-tocopherol concentration in circulation is reduced. Probucol, a recently found drug, induced α-tocopherol deficiency in circulation and was effective against murine malaria. Currently, treatment of malaria relies on the artemisinin-based combination therapy (ACT); however, when mice infected with malarial parasites were treated with probucol and dihydroartemisinin, the beneficial effect of ACT was pronounced. Protective effects of vitamin E deficiency might be extended to manage other parasites in future.

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Antagonistic effect of Vitamin E on the efficacy of artesunate against Plasmodium berghei infection in mice

Cited by 13 publications

References 12 publications

In vitro effects of co-incubation of blood with artemether/lumefantrine & vitamin C on the viscosity & elasticity of blood

In vitro effects of co-incubation of blood with artemether/lumefantrine & vitamin C on the viscosity & elasticity of blood

Probucol dramatically enhances dihydroartemisinin effect in murine malaria

Potential of Vitamin E Deficiency, Induced by Inhibition of α-Tocopherol Efflux, in Murine Malaria Infection

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