scholarly journals Repurposing Dihydroartemisinin-Piperaquine-Doxycycline as an Antimalarial Drug: A Study in Plasmodium berghei-Infected Mice

2021 ◽  
Vol 10 (2) ◽  
pp. 135-140
Author(s):  
Udeme Owunari Georgewill ◽  
Elias Adikwu
Keyword(s):  
Plasmodium Berghei ◽  
Blood Cells ◽  
Low Density Lipoprotein ◽  
White Blood Cells ◽  
Density Lipoprotein ◽  
Negative Control ◽  
New Drugs ◽  
Antiplasmodial Activity ◽  
Lipoprotein Cholesterol ◽  
Plasmodium Parasite

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.

scholarly journals In-vivo Antiplasmodial Activity of Sulfadoxine/Pyrimethamine/Doxycycline on Plasmodium berghei Infected Mice

2021 ◽  
pp. 1-8
Author(s):  
Udeme Owunari Georgewill ◽  
Elias Adikwu
Keyword(s):  
Plasmodium Berghei ◽  
Blood Cells ◽  
Antimalarial Drug ◽  
Low Density Lipoprotein ◽  
White Blood Cells ◽  
Density Lipoprotein ◽  
Negative Control ◽  
Antiplasmodial Activity ◽  
Lipoprotein Cholesterol

The search for newer antimalarial drug combinations is on the front burner due to rising Plasmodium resistance to some currently used antimalarial drugs. This study examined the antiplasmodial activity of sulfadoxine/pyrimethamine/doxycycline (S/P/D) on mice infected with Plasmodium berghei (P. berghei). Swiss albino mice (25-30 g) inoculated with P. bergei (1x107) were treated with D (2.2 mg/kg), S/P (21.4/10.7 mg/kg), and S/P/D for 4 days. The positive and negative controls were treated with normal saline (0.2 ml) and chloroquine (CQ) (10 mg/kg) for 4 days, respectively. After treatment, blood samples were collected and assessed for parasitemia levels and biochemical parameters. The mice were observed for mean survival time (MST). D, S/P, S/P/D and CQ significantly decreased parasitemia in the curative, prophylactic and suppressive tests at p<0.05; p<0.01, p<0.001 and p<0.001, respectively when compared to negative control. In the curative study, 55.9%, 65.1%, and 81.7% parasitemia inhibitions were produced by D, S/P and S/P/D, respectively whereas CQ produced 75.6 % parasitemia inhibition. D, S/P and S/P/D significantly prolonged MST at p<0.05, p<0.01 and p<0.001 respectively when compared to negative control. Altered serum biochemical markers in  P. berghei infected mice were marked by  significantly (p<0.001) decreased  packed cell volume, red blood cells, hemoglobin, high density lipoprotein cholesterol levels with  significantly (p<0.001) increased cholesterol, white blood cells, total cholesterol, low-density lipoprotein cholesterol and triglyceride levels when compared to control. However, D, S/P and S/P/D significantly restored the aforementioned markers at p<0.05, p<0.01 and p<0.001, respectively when compared to negative control. S/P/D may be used as an antimalarial drug.

scholarly journals ANTIPLASMODIAL ACTIVITY OF KETOTIFEN-ARTEMETHER-LUMEFANTRINE ON PLASMODIUM BERGHEI INFECTED MICE

2020 ◽  
Vol 8 (11) ◽  
pp. 251-258
Author(s):  
Udeme O. Georgewill ◽  
Chidi E. Ezeriohaa ◽  
Elias Adikwu
Keyword(s):  
Plasmodium Berghei ◽  
Blood Cells ◽  
Low Density Lipoprotein ◽  
White Blood Cells ◽  
Density Lipoprotein ◽  
Positive Control ◽  
Negative Control ◽  
Lipoprotein Cholesterol ◽  
Survival Times ◽  
Adult Mice

Introduction: The development of new antimalarial drugs is time-consuming and costly, thus repurposing of drugs with initial indications for possible antimalarial indication is imperative. This study assessed the antiplasmodial effect of ketotifen (KT) in combination with artemether/lumefantrine (A/L) in Plasmodium bergei infected mice. Materials and Methods: Adult mice (25-30g) were parasitized with Plasmodium berghei, grouped and treated per oral (p.o) with KT (0.1mg/kg), A/L (2.3/13.7mg/kg) and KT/A/L daily in curative, suppressive and prophylactic studies. The negative control (NC) and the positive control (PC) were treated daily p.o with normal saline (0.2mL) and chloroquine (CQ) (10mg/kg) for 4 days respectively. After treatment, blood samples were collected and assessed for percentage parasitemia level, hematological and lipid parameters. Results: The curative, suppressive and prophylactic studies showed significant decreases in percentage parasitemia levels at KT (0.1mg/kg) (p<0.01), A/L (2.3/13.7 mg/kg) (p<0.001) and KT/A/L (p<0.0001) when compared to negative control. Significant increases in mean survival times occurred at KT (0.1 mg/kg) (p<0.01), A/L (2.3/13.7mg/kg) (p<0.001) and A/L/T (p<0.0001) when compared to negative control. Significant increases in packed cell volume, red blood cells, hemoglobin, high density lipoprotein cholesterol levels with significant decreases in total cholesterol, white blood cells, low density lipoprotein cholesterol and triglyceride levels at KT (28.6 mg/kg) (p<0.05), A/L (2.3/13.7mg/kg) (p<0.01) and KT/A/L (p<0.001) when compared to negative control. Conclusion: KT may be repurposed in combination with A/L for malaria treatment.

Antiplasmodial Activity of Ketotifen-Artemether-Lumefantrine on Plasmodium Berghei Infected Mice

2020 ◽  
Vol 2020 ◽  
Author(s):  
Udeme Georgewill ◽  
Chidi E. Ezerioha ◽  
Elias Adikwu
Keyword(s):  
Plasmodium Berghei ◽  
Blood Cells ◽  
Low Density Lipoprotein ◽  
White Blood Cells ◽  
Density Lipoprotein ◽  
Positive Control ◽  
Negative Control ◽  
Lipoprotein Cholesterol ◽  
Pack Cell Volume ◽  
Survival Times

Introduction: The development of new antimalarial drugs is time-consuming and costly, thus repurposing of drugs with initial indications for possible antimalarial indication is imperative. This study assessed the antiplasmodial effect of ketotifen (KT) in combination with artemether/lumefantrine (A/L) in Plasmodium bergei infected mice. Materials and Methods: Adult mice (25-30g) were parasitized with Plasmodium berghei, grouped and treated per oral (p.o) with KT (0.1mg/kg), A/L (2.3/13.7mg/kg) and KT/A/L daily in curative, suppressive and prophylactic studies. The negative control (NC) and the positive control (PC) were treated daily p.o with normal saline (0.2mL) and chloroquine (CQ) (10mg/kg) for 4 days respectively. After treatment, blood samples were collected and assessed for percentage parasitemia level, hematological and lipid parameters. Results: The curative, suppressive and prophylactic studies showed significant decreases in percentage parasitemia levels at KT (0.1mg/kg) (p<0.01), A/L (2.3/13.7 mg/kg) (p<0.001) and KT/A/L (p<0.0001) when compared to negative control. Significant increases in mean survival times occurred at KT (0.1 mg/kg) (p<0.01), A/L (2.3/13.7mg/kg) (p<0.001) and A/L/T (p<0.0001) when compared to negative control. Significant increases in pack cell volume, red blood cells, hemoglobin, high density lipoprotein cholesterol levels with significant decreases in total cholesterol, white blood cells, low density lipoprotein cholesterol  and triglyceride levels at KT (28.6 mg/kg) (p<0.05), A/L (2.3/13.7mg/kg) (p<0.01) and KT/A/L (p<0.001) when compared to negative control. Conclusion: KT may be repurposed in combination with A/L for malaria treatment.

Antiplasmodial activity of artemether-lumefantrine-tinidazole on Plasmodium berghei infected mice

2020 ◽  
Vol 2020 ◽  
Author(s):  
Udeme Georgewill
Keyword(s):  
Plasmodium Berghei ◽  
Blood Cells ◽  
Hematological Parameters ◽  
White Blood Cells ◽  
Density Lipoprotein ◽  
Positive Control ◽  
Negative Control ◽  
Lipoprotein Cholesterol ◽  
Cholesterol Levels ◽  
The Impact

Introducion: The impact of malaria scourge has been characterized by daunting challenges including antimalarial drug resistance. This necessitates the search for newer antimalaria drugs using approaches including drug repurposing. This study assessed whether Tinidazole (T) can be repurposed as antimalaria in combination with artemether/lumefantrine (A/L) in Plasmodium berghei infected mice. Materials and Methods: Plasmodium berghei infected mice were grouped and orally treated with A/L (2.3/13.7mg/kg), T (28.6 mg/kg), and A/L/T daily in curative, suppressive and prophylactic studies. The negative control (NC) and positive control (MC) were orally treated with 0.9% normal saline (0.2mL) and chloroquine (CQ) (10mg/kg) daily for 4 days, respectively. After drug administration, blood samples were collected and evaluated for parasitemia level, lipid and hematological parameters. Results: Significant decreases in parasitemia levels in the curative, suppressive and prophylactic groups were observed in mice treated with T (28.6 mg/kg) (p<0.05), A/L (2.3/13.7 mg/kg) (p<0.01) and A/L/T (p<0.001) when compared to negative control. Mean survival times were significantly increased at T (28.6 mg/kg) (p<0.05), A/L (2.3/13.7mg/kg) (p<0.01) and A/L/T (p<0.001) when compared to negative control. Red blood cells, hemoglobin, packed cell volume, high density lipoprotein, cholesterol levels were significantly (p<0.001) increased whereas white blood cells, total cholesterol, triglyceride and low density lipoprotein cholesterol levels  were significantly decreased at T (28.6 mg/kg) (p<0.05), A/L (2.3/13.7mg/kg) (p<0.01) and A/L/T (p<0.001) when compared to negative control. The antiplasmodial effect of A/L/T differ significantly (p<0.05) when compared to positive control. Conclusion: This study recommends the repurposing of tinidazole in combination with artemether/lumefantrine for malaria treatment and further studies in humans.

scholarly journals In-vivo Antiplasmodial Effect of Dihydroartemisinin-Piperaquine-Nitrofurantoin on Plasmodium berghei- Infected Mice

2021 ◽  
pp. 12-20
Author(s):  
Udeme O. Georgewill ◽  
Festus Azibanigha Joseph ◽  
Elias Adikwu
Keyword(s):  
Plasmodium Berghei ◽  
Blood Cells ◽  
Hematological Parameters ◽  
White Blood Cells ◽  
Positive Control ◽  
Negative Control ◽  
Antiplasmodial Activity ◽  
Significant Difference ◽  
Tract Infections

Nitrofurantoin (NT) used for the treatment of urinary tract infections may have antiplasmodial activity. Dihydroartemisinin-piperaquine (DP) is an artemisinin based combination therapy used for the treatment of malaria. This study evaluated the antiplasmodial effect of dihydroartemisinin-piperaquine-nitrofurantoin (DP-NT) on mice infected with Plasmodium berghei. Adult Swiss albino mice (30-35 g) of both sexes were used. The mice were randomly grouped, inoculated with Plasmodium berghei, and treated orally with DP (1.7/13.7 mg/kg), NT (57.1 mg/kg) and DP-NT (1.71/13.7/ 57.1 mg/kg), respectively using curative, prophylactic and suppressive tests. The negative control was orally treated with normal saline (0.3 mL), while the positive control was orally treated with chloroquine CQ (10mg/kg). After treatment, blood samples were collected and evaluated for percentage parasitemia, inhibitions and hematological parameters. Liver samples were evaluated for histological changes. The mice were observed for mean survival time (MST). Treatment with DP-NT decreased parasitemia levels when compared to individual doses of DP and NT with significant difference observed at p<0.05. DP-NT prolonged MST when compared to individual doses of DP and NT with significant difference observed at p<0.05. The decrease in packed cell volume, red blood cells, hemoglobin and increase in white blood cells in parasitized mice were significantly restored by DP-NT  when compared to individual doses of DP and NT with difference observed at p<0.05. DP-NT eradicated liver Plasmodium parasite.  NT remarkably increased the antiplasmodial activity of DP. DP-NT may be used for the treatment of malaria.

scholarly journals Triglyceride/High-Density Lipoprotein Cholesterol Ratio is associated with the mortality of COVID-19: An Observational Study

2021 ◽  
Author(s):  
Fei Peng ◽  
Shangjie Wu ◽  
Si Lei ◽  
Quan Zhang ◽  
Yanjun Zhong
Keyword(s):  
High Density Lipoprotein ◽  
High Density Lipoprotein Cholesterol ◽  
Blood Cells ◽  
Hematological Parameters ◽  
White Blood Cells ◽  
Density Lipoprotein ◽  
High Density ◽  
Lipoprotein Cholesterol ◽  
Operating Characteristics ◽  
Cholesterol Ratio

Abstract (1) Background: Triglyceride to high density lipoprotein cholesterol (TG/HDL-c) ratio is crucial when researching metabolic and vascular diseases, and its involvement in COVID-19 was sparsely elaborated on. The purpose of the study was to explore if there were any associations between the TG/HDL-c ratio and COVID-19 prognosis; (2) Methods: A total of 262 COVID-19 patients were retrospectively investigated. The clinical features and baseline hematological parameters were recorded and analyzed; (3) Results: Compared with the survivors, the non-survivors of COVID-19 had significantly higher levels of white blood cells (4.7 vs. 13.0 ×109/L; P < 0.001), neutrophils (3.0 vs. 11.6×109/L; P < 0.001), C-reactive proteins (15.7 vs. 76.7 mg/L; P < 0.001) and TG/HDL-c ratio (1.4 vs. 2.5; P = 0.001). The receiver operating characteristics curve [area under the curve, 0.731; 95% confidence interval, 0.609–0.853; P = 0.001] suggested that the TG/HDL-c ratio could predict the mortality of COVID-19. Moreover, the TG/HDL-c ratio was positively correlated with white blood cells (r = 0.255, P < 0.001), neutrophils (r = 0.243, P < 0.001) and C-reactive proteins (r = 0.170, P < 0.006); (4) Conclusions: Our study demonstrated that TG/HDL-c ratio may potentially be a predictive marker for mortality in COVID-19 patients.

scholarly journals Modulation of Lipoprotein Cholesterol Levels in Plasmodium berghei Malarial Infection by Crude Aqueous Extract of Ganoderma lucidum

Cholesterol ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Olarewaju M. Oluba ◽  
Augustine O. Olusola ◽  
George O. Eidangbe ◽  
Leye J. Babatola ◽  
E. Chukwu Onyeneke
Keyword(s):  
Normal Control ◽  
Aqueous Extract ◽  
Plasmodium Berghei ◽  
Ganoderma Lucidum ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Low Density ◽  
Malarial Infection ◽  
Dose Dependent

In this study, attempt is made to establish changes in serum and liver lipoprotein cholesterols accompanying Plasmodium berghei malarial infection in mice treated with aqueous extract of Ganoderma lucidum at 100, 250, and 500 mg/kg body weight in comparison with 15 mg/kg chloroquine (CQ). Significant increases in all the lipoprotein fractions were observed in infected untreated mice compared with normal control mice. Treatment with 100 and 250 mg/kg G. lucidum extract produced significant reduction in serum total cholesterol (TC) and low-density cholesterol (LDL-C) contents compared with 500 mg/kg G. lucidum and CQ. Treatment with CQ, however, produced significant reduction in hepatic TC and LDL-C compared with the extract. A dose-dependent significant increase in serum high-density lipoprotein cholesterol (HDL-C) was observed in the G. lucidum treated mice compared with normal control but significantly lower compared with CQ-treated mice. Liver HDL-C level was significantly higher in CQ-treated mice compared with normal control and significantly lower compared with G. lucidum-treated and infected untreated mice. A dose-dependent effect of the extract was observed in both serum and liver very-low density lipoprotein cholesterol (VLDL-C). The implication of these results is discussed with respect to the parasite survival and proliferation in the serum and liver.

A comparative study between olive oil and Nigella Sativa oil in treatment of hyperlipidemia induced in male albino mice

2014 ◽  
Vol 38 (2) ◽  
pp. 123-127
Author(s):  
Lubna Ahmed Kafi
Keyword(s):  
Olive Oil ◽  
Nigella Sativa ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Positive Control ◽  
Negative Control ◽  
Lipoprotein Cholesterol ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Nigella Sativa Oil

     This study was conducted on 20 adult mice which were divided randomly in to 4 equal groups. The first group served as negative control (NC) that received the diluent (sun flower oil), while hyperlipidemia was induced in the other three groups, the second group received the diluent and considered as positive control (PC), while group three and four were treated with olive oil (OO) or Nigella sativa oil (NSO) at a dose of 0.4ml/kg BW orally, respectively for two months. At the end of experiment and fasting overnight, lipid profile which included (total cholesterol TC, triglyceride TG, high density lipoprotein cholesterol HDL-C, low density lipoprotein cholesterol LDL-C and very low density lipoprotein cholesterol VLDL-C) were measured. The results indicated significant (P<0.05) improvement in all these parameters as compare to the positive control, while the value of HDL-C was significantly higher in the olive oil treated group as compared with all groups including negative control group.

scholarly journals Emerging Non-statin Treatment Options for Lowering Low-Density Lipoprotein Cholesterol

2021 ◽  
Vol 8 ◽  
Author(s):  
Chandni Bardolia ◽  
Nishita Shah Amin ◽  
Jacques Turgeon
Keyword(s):  
Cardiovascular Disease ◽  
Adverse Drug Events ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
New Drugs ◽  
Lipoprotein Cholesterol ◽  
Atherosclerotic Cardiovascular Disease ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Pcsk9 Inhibitors

Low-density lipoprotein cholesterol (LDL-C) is a modifiable risk factor for the development of atherosclerotic cardiovascular disease. Statins have been the gold standard for managing cholesterol levels and reducing the risks associated with atherosclerotic cardiovascular disease; however, many patients do not achieve their cholesterol goals or are unable to tolerate this drug class due to adverse drug events. Recent studies of non-statin cholesterol lowering drugs (i.e., ezetimibe, PCSK9 inhibitors) have demonstrated cardiovascular benefits; and new drugs [i.e., bempedoic acid (BDA), inclisiran] have produced promising results in pre-clinical and clinical outcome trials. This narrative review aims to discuss the place in therapy of ezetimibe, PCSK9 inhibitors, BDA, and inclisiran and describe their relative pharmacokinetic (PK) profiles, efficacy and safety as monotherapy and combination therapy, and cardiovascular benefit(s) when used for hypercholesterolemia.

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