Udeme Owunari Georgewill
Department of Pharmacology, Faculty of Basic Clinical Sciences, University of Port Harcourt, Rivers State

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Repurposing Dihydroartemisinin-Piperaquine-Doxycycline as an Antimalarial Drug: A Study in Plasmodium berghei-Infected Mice Udeme Owunari Georgewill; Elias Adikwu
Biology, Medicine, & Natural Product Chemistry Vol 10, No 2 (2021)
Publisher : Sunan Kalijaga State Islamic University & Society for Indonesian Biodiversity

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14421/biomedich.2021.102.135-140

Abstract

Artemisinin-based combination (ACT) therapy is the mainstay for malaria treatment. However, Plasmodium parasite with decreased susceptibility to ACT has emerged. Hence, it is imperative to discover new drugs or explore new drug combinations that can decrease Plasmodium parasite resistance. This study assessed the antiplasmodial activity of dihydroartemisinin-piperaquine- doxycycline (D-P-DX) on mice infected with Plasmodium berghei. Swiss albino mice (25-30g) of both sexes inoculated with 1x107 Plasmodium berghei intraperitoneally were used. The mice were randomly grouped and orally treated with DX (2.2 mg/kg), D-P (1.71/13.7 mg/kg) and D-P-DX daily in curative, suppressive and prophylactic studies. The negative and the positive controls were treated daily with normal saline (0.2mL) and chloroquine (CQ) (10mg/kg), respectively. After treatment, blood samples were assessed for percentage parasitemia, hematological and lipid parameters. Also, the mice were observed for mean survival time. D-P, DX, and D-P-DX produced significant decreases in percentage parasitemia at p<0.05, p<0.01 and p<0.001, respectively when compared to negative control. In the curative study, D-P, DX, and D-P-DX produced 64.9%, 71.1%, and 93.6% parasitemia inhibitions when compared to 70.0% inhibition produced by CQ. Plasmodium berghei -induced alterations in packed cell volume, white blood cells, red blood cells, hemoglobin, high-density lipoprotein cholesterol, total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels were significantly restored by DX (p<0.05) and D-P (p<0.01) and D-P-DX (p<0.001) when compared to the negative control. D-P-DX showed significant antiplasmodial activity against Plasmodium berghei- infected mice. It may be clinically useful for the treatment of malaria.
Potential Antimalarial Activity of Artemether/Lumefantrine/Doxycycline: A Study in Mice Infected with Plasmodium berghei Udeme Owunari Georgewill; Elias Adikwu
Biology, Medicine, & Natural Product Chemistry Vol 11, No 1 (2022)
Publisher : Sunan Kalijaga State Islamic University & Society for Indonesian Biodiversity

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14421/biomedich.2022.111.1-6

Abstract

Antimalarial drug resistance is one of the greatest challenges towards eradicating malaria. Exploring new combination therapies can overcome resistance challenges. The present study examined the antiplasmodial effect of artemether/lumefantrine/doxycycline (A/L/D) on a mouse model infected with Plasmodium berghei. Adult Swiss albino mice (22-30g) intraperitoneally infected with blood containing 1x107 Plasmodium berghei were randomly grouped and orally treated daily with D (2.2 mg/kg), A/L (1.71/13.7 mg/kg) and A/L/D. The negative control was treated daily with normal saline (0.2ml) whereas the positive control was treated daily with chloroquine (CQ) (10mg/kg). After treatment, blood samples were assessed for percentage parasitemia and biochemical parameters. Mice were observed for mean survival time (MST). D, A/L and A/L/D produced significant decreases in percentage parasitemia levels at p<0.05; p<0.01 and p<0.001, respectively when compared to negative control. In the curative test, D, A/L and A/L/D produced 60.4%, 70.3%, and 90.0% parasitemia inhibitions, respectively whereas CQ produced 76.0% parasitemia inhibition. D, A/L, A/L/D and CQ produced 63.2 %, 80.1%, 92.3% and 83.6% parasitemia inhibitions, respectively in the suppressive test. D, A/L, and A/L/D prevented Plasmodium berghei-induced alterations in biochemical parameters by increasing packed cell volume, red blood cells, hemoglobin, and high-density lipoprotein and decreasing white blood cells, total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels significantly at p<0.05 and p<0.01 and p<0.001, respectively when compared to the negative control. A/L/D produced significant antiplasmodial activity therefore, it may be used clinically for the treatment of malaria.