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 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.

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 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 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 Modulatory effects of rutin on biochemical and hematological parameters in hypercholesterolemic Golden Syrian hamsters

2009 ◽  
Vol 81 (1) ◽  
pp. 67-72 ◽  
Author(s):  
Alexandre Kanashiro ◽  
Daiani C.O. Andrade ◽  
Luciana M. Kabeya ◽  
Walter M. Turato ◽  
Lucia H. Faccioli ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Inflammatory Diseases ◽  
Hematological Parameters ◽  
White Blood Cells ◽  
Density Lipoprotein ◽  
Plasma Triglyceride ◽  
New Drugs ◽  
High Fat ◽  
Syrian Hamsters ◽  
Cholesterol Levels

Flavonoids have been reported to exhibit several pharmacological properties, mainly in cardiovascular and inflammatory diseases. In the present study, we observed that rutin, a known glycosylated flavonoid isolated from Dimorphandra mollis, had a lowering effect on plasma triglyceride levels of diet-induced hypercholesterolemic Golden Syrian hamsters, but did not change total cholesterol and high-density lipoprotein cholesterol levels. Moreover, high-fat or rutin supplemented diets showed no immunotoxic effects, since no significant changes were observed on total white blood cells, granulocytes and mononuclear cells, as well as on the neutrophil apoptosis degree, when compared to untreated animals. Therefore, rutin seems to be a selective and non-toxic modulator of hypercholesterolemia, which can be promising for the development of new drugs.

scholarly journals Effect of Quercetin on Haematobiochemical and Histological Changes in the Liver of Polychlorined Biphenyls-Induced Adult Male Wistar Rats

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Kandaswamy Selvakumar ◽  
Senthamilselvan Bavithra ◽  
Sekaran Suganya ◽  
Firdous Ahmad Bhat ◽  
Gunasekaran Krishnamoorthy ◽  
...  
Keyword(s):  
Blood Cells ◽  
Hematological Parameters ◽  
White Blood Cells ◽  
Density Lipoprotein ◽  
Protective Role ◽  
Low Density Lipoproteins ◽  
Gamma Glutamyl Transferase ◽  
Low Density ◽  
Very Low Density Lipoproteins ◽  
Glutamyl Transferase

Polychlorinated biphenyls exposure damages the rat liver cells. Hematological parameters such as hemoglobin, packed cell volume, red-blood cells, white-blood cells, neutrophils, platelet counts, and RBC indices were significantly decreased. Polymorphs, eosinophil counts, and erythrocyte sedimentation rate were significantly increased. Serum liver enzymes such as aspartate transaminase, alanine transaminase, alkaline phosphatase, and gamma-glutamyl transferase were increased by PCBs treatment. Serum lipid profiles such as cholesterol, triglycerides, low-density lipoproteins and very-low-density lipoproteins were increased in PCBs-treated rats. High-density lipoprotein, total protein, albumin, globulin levels, and albumin/globulin ratio were also decreased after PCB exposure. Then levels of sodium, potassium, chloride, and bicarbonate were also altered. Serum glucose levels were increased along with total bilirubin after PCBs exposure. Simultaneous quercetin supplementation significantly protected the PCBs-induced changes of hematobiochemical parameters. Thus, quercetin shows a protective role against PCBs-induced alterations in the hematological and biochemical parameters.

scholarly journals Antimalaria assay of fruit extract of Morinda citrifolia and activity of mice (Mus musculus) macrophage after infecting it with Plasmodium berghei

2005 ◽  
Vol 3 (2) ◽  
pp. 61-69
Author(s):  
RAHADI HUTOMO ◽  
SUTARNO SUTARNO ◽  
WIEN WINARNO ◽  
KUSMARDI KUSMARDI
Keyword(s):  
Plasmodium Berghei ◽  
Blood Cells ◽  
World Wide ◽  
Positive Control ◽  
Negative Control ◽  
Morinda Citrifolia ◽  
Distilled Water ◽  
Inhibition Activity ◽  
Fruit Extract ◽  
Macrophage Activity

Malaria is a world wide disease. Death resulting from the disease was caused by the parasite’s resistance to the malaria drugs and the problem of immune system. The aims of the research were to know the effect of M. citrifolia fruit extract to Plasmodium berghei on total red blood cells of mice, and to know the effect of the extract on the number of intraperitoneal macrophage phagocytosing latex after infected by P. berghei. Three doses of fruit extract, 200, 150, 100 mg/kg BB were used in this study. Fansidar was used as positive control, while distilled water was used as negative control. The result of this research indicated that dose of 200 mg/kg BB could reduce number of parasitemia to 3.576%, dose of 150 mg/kg BB to 4.107%, and dose of 100 mg/kg BB to 13.331% on day 5, and could not reduce any number of parasitemia on the next day. Inhibition by Fansidar reached 0.201%, while distilled water did not show any inhibition activity. Different macrophage activity on phagocytosing latex was taken place. The average of macrophage activity on phagocytosing latex at dose of 200 mg/kg BB was 3.8x106 cell, at dose of 150 mg/kg BB was 2.53x106 cell/mL, while at dose 100 mg/kg BB was 1.5x106 cell/mL, and 2.43x106 cell/mL for the control. Based on the results of the study, it can be concluded that the reduction of the number of parasitemia taken place at dose 200 and 150 mg/kg BB, although its activity is much lower than malaria drug of Fansidar. Macrophage activities increased at dose of 200 mg/kg BB.

scholarly journals VAKSIN INAKTIF Klebsiella pneumoniae DENGAN PERLAKUAN SINAR GAMMA DAN PEMANASAN SUHU 65° C

2010 ◽  
Vol 15 (2) ◽  
pp. 151-157
Author(s):  
I. Djajanegara ◽  
I. Sugoro
Keyword(s):  
Klebsiella Pneumoniae ◽  
Blood Cells ◽  
Vaccine Candidate ◽  
White Blood Cells ◽  
Challenge Test ◽  
Positive Control ◽  
Negative Control ◽  
Cow Milk ◽  
Coliform Bacteria ◽  
Nuclear Technique

Klebsiella pneumoniae is one of coliform bacteria which cause human dan mammalian diseases. The bacteria dominate in dairy cow milk which has suffered from mastitis and has resistent on antibiotic. Vaccination is one of aims to prevent the diseases. Nuclear technique could be used to have a vaccine candidate. This research was conducted to get the influence of inactivated K. pneumoniae by gamma irradiated and heat inactivated as vaccine candidate on mice. The treatment were positive control (infected by K. pneumoniae), Negative control (injection by physiologies NaCl solution), 800 Gy (infected by K. pneumoniae has inactivated with 800 Gy), 1000 Gy (infected by K. pneumoniae has inactivated with 1000 Gy), 30’ (infected by K. pneumonia has inactivated with heat 65° C for 30’), and 45’ (infected by K. pneumoniae has inactivated with heat 65° C for 30’). The parameters were physical condition, weight, organ, total number of red, white blood cells, and intraperitoneal macrophage. The results showed that irradiated vaccines were better than heat. % mortality of positive control was 100% but the treatments were 0%. The physic condition of mice was normal for irradiated treatment, but not for negative control and heat treatment. The weight gain of mice after vaccination and challenge test were decreased and back normal after 2 days. The organ condition of mice was normal after vaccination and challenge test. The total number of red and white blood cells showed the same pattern for all treatment after vaccination and challenge test, but the total of intraperitoneal macrophage was increased after 4 hours vaccination. Based on the results showed that irradiated vaccine has potential to develop as vaccine candidate.

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