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

Author(s):  
Udeme O. Georgewill ◽  
Festus Azibanigha Joseph ◽  
Elias Adikwu

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.

Author(s):  
Udeme Owunari Georgewill ◽  
Elias Adikwu

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.


2020 ◽  
Vol 2020 ◽  
Author(s):  
Udeme Georgewill

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.


2021 ◽  
Vol 8 (2) ◽  
pp. 026-033
Author(s):  
Michael Okpara Elom ◽  
Anthony Gideon Uche ◽  
Boniface Nwofoke Ukwah ◽  
Victor Udoh Usanga ◽  
Anthonia Ifeoma Okpara-Elom ◽  
...  

Antiplasmodial effect of Citrus limon and Citrus paradisi extracts on Plasmodium berghei-infected mice was studied. Twenty five albino mice were randomized into five categories of G, L, GL, ACT (positive control) and NC which stand for grape, lemon, grape and lemon combined extracts, artemisinin combined therapy and negative control respectively. The NC group did not receive any intervention. Other treatments were administered orally for 12 days whereas administration of ACT lasted for 3 days. Blood was collected from the tail vein of the mice at a three day interval through venipuncture. Thick blood films were prepared and parasite densities were estimated using standard parasitological techniques. Results were analysed with ANOVA and Duncan multiple range tests. There was no significant difference (p>0.05) between parasite densities of the treatment groups and the negative control at baseline levels. However, as the treatment progressed from day 3 through day 9, there were significant reductions (p<0.05) in parasite densities among treatment groups when compared to the negative control. In this study, extracts of C. limon and C. paradisi in both single and combined strengths have been found to have antiplasmodial properties in mice. ACT possessed the highest antiplasmodial effect while C. limon as a single treatment ranked second in possession of antiplasmodial activity but exhibited increased RBC lysis. In combination, C. limoni and C. paradise extracts showed antiplasmodial activity that is slightly less than that exhibited by the lemon extract alone, but maintained normal RBC morphology whereas C. paradisi extract alone exhibited the lowest level of parasite clearance with atrophied red blood cells. Investigation of the effects of the extracts on liver, kidney and gastrointestinal tissues of mice is recommended before they could be prescribed as antimalaria for other animals and humans.


2021 ◽  
Vol 10 (2) ◽  
pp. 135-140
Author(s):  
Udeme Owunari Georgewill ◽  
Elias Adikwu

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.


Author(s):  
Afolabi Owoloye ◽  
Olusegun Matthew Akanbi ◽  
Oluwafemi Shittu Bakare

Aim: This study aimed to investigate the antiplasmodial activity and effect of stem bark of Terminalia avicennioides made as dietary feed fed to mice infected with Plasmodium berghei, on some serum biochemistry. Methodology: Twenty (20) mice were divided into four groups. Group 1 was not infected with Plasmodium berghei (normal control), Group 2 was infected with P. berghei but not treated (negative control). Group 3 was infected and treated with 5.0 mg/kg of Arthemeter-Lumefantrine (positive control). Groups 4 was infected and fed with treated feed (T. avicennioides). Treatments were carried out for five days. Blood was taken daily from the tail of the mice before treatment for the assessment of parasitaemia. The animals were sacrificed on the fifth day and the whole blood was collected into EDTA bottle. Serum obtained was used to assay for biochemical parameters. Results: Parasitaemia count was significantly lower (p<0.05) in all the treated groups when compared with the negative control group. The high-density lipoprotein was significantly higher (P<0.05) in the normal control (123.14±3.19) when compared with the positive control (99.18±2.76), negative control (85.29±0.85) and the group treated with T avicennioides (86.14±3.21). The serum alanine aminotransferase, alkaline phosphatase and aspartate aminotransferase level in the group treated with T. avicennioides (167.90±4.13, 15.87±1.32 and 17.50±1.95) respectively were significantly reduced (p<0.05) when compared with the negative control (197.25±5.44, 20.01±1.32 and 26.71±0.45) respectively. The mean bilirubin and albumin level in the negative control showed no significant difference when compared with the group fed with T. avicennioides. Conclusion: The study concluded that T. avicennioides have antiplasmodial activity with a mild adverse effect on liver function.


2020 ◽  
Vol 8 (11) ◽  
pp. 251-258
Author(s):  
Udeme O. Georgewill ◽  
Chidi E. Ezeriohaa ◽  
Elias Adikwu

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.


Author(s):  
Asakizi Augustine Nji ◽  
Nchang Chrysanthus ◽  
Ngombe David Monyongo

This study is design to ascertain the hematological status in albino mice treated with Justicia carnea leave, which could aid in the treatment of anemia. The hematological parameters investigated include Mean Cell Volume (MCV), Mean Cell Hemoglobin (MCH), Mean Cell Hemoglobin Concentration (MCHC), Platelets (PLTS), Hemoglobin (Hb), Red Blood Cells (RBCs), Pack Cell Volume (PCV) and White Blood Cells (WBCs). Nine (9) male albino mice of approximately the same weight 300 g were grouped into 3 groups that’s Negative Control (NC) Positive Control (PC) and Test Control (TC), each made up of 3 mice. Negative control mice were given normal feed moisten with water,  Positive control received diluted iron folate with normal feed, finally Test control mice were  administered powdered leaves of Justicia carnea with normal feed for 7 days, after which blood samples were collected using EDTA tubes by exsanguination and run for hematological parameters using auto-hematological analyzer. The results of various groups were found to be; as there was a significant increase in RBCs, Hb, & PCV (P=0.05), between the groups. No significant change was observed on the MCV, MCH, and MCHC. Lymphocytosis was observed in all groups with mark difference in granulocytosis. TC had granulocytosis, NC showed normal granulocyte scores and the PC show granulocytopenia with a statistical difference of P=0.0017. A significant difference was seen in platelets between the groups P=0.02. This study shows that J. carnea leaves possess anti-anemic potential, lending credence to the use of these plant leaves in folk medicine for the management of hemolytic anemia would be helpful. Further research on the various phytochemicals of the plant should be done and also its toxicological aspects.


2020 ◽  
Vol 2020 ◽  
Author(s):  
Udeme Georgewill ◽  
Chidi E. Ezerioha ◽  
Elias Adikwu

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.


Author(s):  
A. Abilov ◽  
A. Azhmyakov ◽  
I. Novgorodova ◽  
N. Bogolyubova

Purpose: to study hematological parameters of blood in bulls-producers of dairy breeds on the day of semen collection in the Udmurt Republic after a long winter period of operation, depending on the breeds, age and place of selection.Materials and methods. The work was performed at the Federal Research Center for Animal Husbandry named after Academy Member L. K. Ernst on the basis of AO "Udmurtplem" of the Udmurt Republic in the period from 2020 to 2021 on dairy bulls (n=20) aged 15-69 months, including a purebred Holstein breed of domestic selection (n=6), a Holstein black-and-white breed of European selection (the Netherlands, n=6), a black-and-white breed with blood transfusion on Holsteins on at the level of 94-98% (n=8). The content of white blood cells, red blood cells, hemoglobin and hematocrit, depending on age and breed, was studied on the ABC VET hematological analyzer on the day of taking the seed.Results. It was found that on average, in 20 bulls aged 15-69 months, the level of white blood cells was at the level of reference values of 8.8±0.25 x 109/l, red blood cells 10.3 x 1012/l, which is 50% more than the reference values. The concentration of hemoglobin is 128.0±2.92 g/l, hematocrit is on average 54.3%, with a norm of 24-46%. Breeding bulls at a reliable level, differing in age, showed that some animals had high indicators for red blood cells of 10.3±0.26 x 102, for hematocrit of 54.3% against 24-46% of reference values. Also, according to hematological indicators, there was a tendency to increase the concentration of hemoglobin and hematocrit in European-bred bulls.Conclusion. The study of the variability in hematological parameters depending on the selection showed that there is no significant difference in leukocytes and all indicators are at the level of reference values, and in erythrocytes more than 50% than the highest indicators. The highest hemoglobin values were at the level of 141-156 g/l instead of 128 g/l according to the highest reference values. Hematocrit also showed high max values in all groups in comparison with the reference values of 59-66% versus 46% in the norm. It is necessary when analyzing hematological blood parameters in addition to the average statistical indicators (M+m) also, monitor the variability (min-max) in order to obtain more objective information.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jonathan Vigne ◽  
Sylvie Bay ◽  
Rachida Aid-Launais ◽  
Guillaume Pariscoat ◽  
Guillaume Rucher ◽  
...  

AbstractThere is a need for new targets to specifically localize inflammatory foci, usable in a wide range of organs. Here, we hypothesized that the cleaved molecular form of CD31 is a suitable target for molecular imaging of inflammation. We evaluated a bioconjugate of D-P8RI, a synthetic peptide that binds all cells with cleaved CD31, in an experimental rat model of sterile acute inflammation. Male Wistar rats were injected with turpentine oil into the gastrocnemius muscle two days before 99mTc-HYNIC-D-P8RI (or its analogue with L-Proline) SPECT/CT or [18F]FDG PET/MRI. Biodistribution, stability study, histology, imaging and autoradiography of 99mTc-HYNIC-D-P8RI were further performed. Biodistribution studies revealed rapid elimination of 99mTc-HYNIC-D-P8RI through renal excretion with almost no uptake from most organs and excellent in vitro and in vivo stability were observed. SPECT/CT imaging showed a significant higher 99mTc-HYNIC-D-P8RI uptake compared with its analogue with L-Proline (negative control) and no significant difference compared with [18F]FDG (positive control). Moreover, autoradiography and histology revealed a co-localization between 99mTc-HYNIC-D-P8RI uptake and inflammatory cell infiltration. 99mTc-HYNIC-D-P8RI constitutes a new tool for the detection and localization of inflammatory sites. Our work suggests that targeting cleaved CD31 is an attractive strategy for the specific in vivo imaging of inflammatory processes.


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