Investigating the comparative effects of six artemisinin-based combination therapies on Plasmodium-induced hepatorenal toxicity

Edagha, Innocent A.; Ekpo, Arit; Edagha, Edelungudi I.; Bassey, Joy V; Nyong, Titus P; Akpan, Anthony S; Obeten, Rose F; Okon, Anthony S; Ating, Blessing A

doi:10.4103/nmj.nmj_152_18

Cited by 7 publications

(7 citation statements)

References 43 publications

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“…The ACTs used in the present study were more neurotoxic to the hippocampal CA 1 compared to the cerebellum, with ASP, DP APy and AL more neurotoxic than AP, AA and AM. Similar findings were reported even in the midst of Plasmodium bergheiinduced hyperparasitemia in rodentia experimental malaria study on the vital organs of first-pass demonstrating that ACTs markedly increased liver transaminases and altered hepato-renal histoarchitectures with ASP, DP and AL-administered groups with impoverished outcomes when compared to AP, AM and AA antimalarials as reported by Edagha et al, [69].…”

Section: Discussionsupporting

confidence: 86%

“…Some vital first line of defense for body include superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and peroxiredoxins which constitute the enzymatic antibodies [17]. ACTs has been reported to alter the enzymatic and nonenzymatic antioxidants concentrations [18][19][20] and exposing the cells to oxidative stress [20].…”

Section: Introductionmentioning

confidence: 99%

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Comparative Brain Microanatomical and Neurochemical Alterations Following the Administration of Seven Oral Artemisinin-Based Combination Therapies in Swiss Mice

Edagha,

Douglas,

Peter

et al. 2024

IJAR

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Over a decade after artemisinin-based combination therapy (ACT) approval as the most preferred anti-malarial drug. Seven ACTs can be sourced as over-the-counter medications in most African pharmacies without prescription. A comparative neurotoxicity of these ACTs was investigated in an in vivo experimental model. Swiss mice numbering 40, weighing 18 - 26 g were allotted to eight groups (n = 5). Group 1 (normal control [NC]), received distilled water 10 mL, while groups 2 to 8 were administered (5.71 mg artesunate+amodiaquine [AA]); (19.29 mg artesunate+mefloquine [AM]); (10.36 mg artesunate+sulfadoxine+pyrimethamine [ASP]); (19.29 mg artesunate+pyronaridine [APy]); (12.5 mg artemisinin+piperaquine [AP]); (15.42 mg dihydroartemisinin+piperaquine [DP]); and (8 mg artemether+lumefantrine [AL]) per kg body weights, respectively orally for 3 days, but for 2 days in group 6. Animals were sacrificed 24 hrs after last administration under ketamine anaesthesia (100 mg/kg, i.p), and excised brains were evaluated for neurochemical and neurohistological alterations. Oxidative stress markers: malondialdehyde and reduced glutathione significantly (p < 0.05) increased as well as antioxidant enzymes glutathione peroxidase, catalase, superoxide dismutase in ACT-administered groups compared to NC. Neurohistology of hippocampal cornu ammonis 1 (CA1) and cerebellum demonstrated vacuolations, neuronal hypertrophy and atrophy pyramidal, and Purkinje neurons. Immunohistochemistry with glial fibrillary acidic protein antibody demonstrated mild to mostly severe astrogliosis in the ACT-administered groups. In conclusion, oxidative stress markers and antioxidants were elevated in the order DP>APy>AP>ASP>AA>AL>AM. Together with the neurohistology, neurotoxicity were in the order DP>ASP>APy>AP>AL>AA>AM particularly in the hippocampus compared to the cerebellum. KEYWORDS: Artemisinin-based combination therapies, Cerebellum, CA1 region of the hippocampus, Neurodegeneration, Oxidative stress.

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Section: Discussionsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Comparative Brain Microanatomical and Neurochemical Alterations Following the Administration of Seven Oral Artemisinin-Based Combination Therapies in Swiss Mice

Edagha,

Douglas,

Peter

et al. 2024

IJAR

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“…In severe infections of malaria caused by P. falciparum among humans, involvement of the liver is common and significant cause of morbidity and mortality (Viriyavejakul et al, 2014). Likewise, in malaria research, rodent models have been pivotal for studying liver syndromes that follow malaria infection (De Niz and Heussler, 2018;Edagha et al, 2019). Notably is the notion that the liver stage of plasmodium is a critical checkpoint for development of CM (Sato et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Treatment of Experimental Cerebral Malaria by Slow Release of Artemisone From Injectable Pasty Formulation

et al. 2020

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Malaria caused by Plasmodium falciparum causes numerous cases of morbidity with about 400,000 deaths yearly owing, mainly, to inflammation leading to cerebral malaria (CM). CM conventionally is treated by repetitive administration of anti-plasmodial drugs and supportive non-specific drugs, for about a week. A mouse model of CM caused by Plasmodium berghei ANKA, in which brain and systemic clinical pathologies occur followed by sudden death within about a week, was used to study the effect of artemisone, a relatively new artemisinin, within an injectable pasty polymer formulated for its controlled release. The parasites were exposed to the drug over several days at a non-toxic concentrations for the mice but high enough to affect the parasites. Artemisone was also tested in cultures of bacteria, cancer cells and P. falciparum to evaluate the specificity and suitability of these cells for examining the release of artemisone from its carrier. Cultures of P. falciparum were the most suitable. Artemisone released from subcutaneous injected poly(sebacic acid-ricinoleic acid) (PSARA) pasty polymer, reduced parasitemias in infected mice, prolonged survival and prevented death in most of the infected mice. Successful prophylactic treatment before infection proved that there was a slow release of the drug for about a week, which contrasts with the three hour half-life that occurs after injection of just the drug. Treatment with artemisone within the polymer, even at a late stage of the disease, helped to prevent or, at least, delay accompanying severe symptoms. In some cases, treatment prevented death of CM and the mice died later of anemia. Postponing the severe clinical symptoms is also beneficial in cases of human malaria, giving more time for an appropriate diagnosis and treatment before severe symptoms appear. The method presented here may also be useful for combination therapy of anti-plasmodial and immunomodulatory drugs.

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“…Jayakumal et al [40] and Ekong et al [41] reported significant weight reduction in relation to use of G. latifolium. The extract at the dose of administration may have interfered with factors that affect availability, intake of food and growth rate [42,43].…”

Section: Median Lethal Dose Of Azadirachta Indica and Gongronema Lati...mentioning

confidence: 99%

Ameliorative Potential of Azadirachta indica and Gongronema latifolium on Plasmodium-induced Gonadotoxicity in Swiss Mice

Peter,

Edagha,

Peter

et al. 2023

IJAR

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Background: Polyherbal decoctions are frequently utilized by some Africans for anti-malaria treatment because they are readily accessible, and assumed low toxicity despite possible gonadotoxicities. We investigated ameliorative potential of anti-plasmodial plants Azadirachta indica (AI) and Gongronema latifolium (GL) on Plasmodium-induced gonadotoxities. Materials and methods: Adult male Swiss mice (n = 50) were allotted into 10 groups of (n = 5) animals. All groups were parasitized with 1 × 106P. berghei inoculum for three days except for groups 1 and 10; (normal control [NC]) and (non-parasitized mice administered Arthemeter-Lumefantrine [AL]). Group 2 was parasitized non-treated (PNT), groups 3 and 4 received low and high doses AI (86.60 and 259.81 mg), groups 5 and 6 received low and high doses GL (337.27 and 1011.80 mg), Groups 7, and 8 received low doses AI + GL (86.60 + 337.27 mg), and high doses AI + GL (259.81 + 1011.80 mg), while Group 9 received AL (8 mg), all odes via oral gavage per kg body weights, respectively. Rectal temperature, seminal/hormonal, testicular morphometry and histology assessments were evaluated using standard protocols. Results: Concurrent administration of AI and GL alleviated pyrexia and parasitemia in test groups, compared to NC and PNT groups. Testosterone concentrations were reduced in parasitized groups compared to NC, while sperm parameters significantly decreased (p < 0.05) in PNT and high AI + GL extract groups, but improved in combined low dose with testicular histoarchitecture. Conclusions: AI and GL concurrently administered at low doses mitigate P. berghei-induced gonadotoxicity better than as singly. KEYWORDS: Anti-Malaria, Azadirachta Indica, Gongronema Latifolium, Gonadotoxicity, Histology.

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Investigating the comparative effects of six artemisinin-based combination therapies on Plasmodium-induced hepatorenal toxicity

Cited by 7 publications

References 43 publications

Comparative Brain Microanatomical and Neurochemical Alterations Following the Administration of Seven Oral Artemisinin-Based Combination Therapies in Swiss Mice

Comparative Brain Microanatomical and Neurochemical Alterations Following the Administration of Seven Oral Artemisinin-Based Combination Therapies in Swiss Mice

Treatment of Experimental Cerebral Malaria by Slow Release of Artemisone From Injectable Pasty Formulation

Ameliorative Potential of Azadirachta indica and Gongronema latifolium on Plasmodium-induced Gonadotoxicity in Swiss Mice

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