A comparative study of the chemotherapeutic effects of diminazene aceturate and Ivermectin on Trypanosoma brucei brucei infected rats

Osondu, Fredrick; Ugochukwu, Chukwuebuka Iniobong Ikenna; Ugochukwu, Emmanuel Ikenna

doi:10.1016/s2222-1808(15)61043-x

Cited by 3 publications

(5 citation statements)

References 23 publications

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“…The parasites appeared in the blood stream 4 to 5 days post infection agreeing with previous work by Ihedioha et al, (2010); Adieme et al, (2014); Osondu et al, (2016). The clinical signs observed in the mice, such as: anemia, anorexia, rough hair coat, emaciation, dullness, depression, pyrexia and pale mucous membrane were similar to those reported in Trypanosoma brucei brucei infection in mice, dogs, rabbits and goats by Anene et al,(1999b); Ezeokonkwo and Agu, (2004); Amadi et al,(2015).…”

Section: Discussionsupporting

confidence: 91%

Comparative effects of graded doses of diaminanzine ace-turate and fixed doses of levamisole in the treatment of albino mice experimentally infected with Trypanosoma brucei brucei

Ijomanta

Ugochukwu

2016

J. Exper. Appl. Anim. Sci.

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Trypanosomosis is a widespread and important disease of animals and humans in tsetse-infested areas of Africa, Nigeria inclusive. To investigate the comparative effects of graded doses of Diaminazine aceturate (DA) and fixed doses of Levamisole in the treatment of albino mice experimentally infected with field isolates of Trypanosoma brucei brucei. Thirty adult mice were used and were randomly divided into 6 groups of 5 mice each. After infection has been established, 3 groups (A, B and C) were treated with graded doses of DA at 7, 14 and 21mg/kg body weight respectively and a fixed dose of Levamisole at 7.5mg/kg body weight, whereas group D was treated with Levamisole only at the same dose. Group E served as positive (infected untreated) control while group F served a negative (uninfected untreated) control. The following parameters were used to access the efficacy of the drugs: weekly rectal temperature, weight changes, packed cell volume, haemoglobin concentration, clinical signs or survivabilty and parasitaemia. The parasite cleared from groups A, B and C by the 48th hour post treatment, but remained in group D while all the mice in group E died within 65 days PI, those in group D died within 65 days PI, whereas those in Group D died within 35 days post treatment. Relapse infection was only recorded in group A at day 30 post treatment. There was no relapse in group B and C, but more deaths were recorded in group C. The significant reduction (p<0.05) in the weight, PCV and haemoglobin concentration and an increase in rectal temperature following infection was reversed by the treatments in groups A, B and C. The results obtained show that an increased dose of DA at 14mg/kg body weight and Levamisole at 7.5mg/kg body weight proved most effective in the treatment of clinical cases of infection with Trypanosoma brucei brucei.

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Section: Discussionsupporting

confidence: 91%

Comparative effects of graded doses of diaminanzine ace-turate and fixed doses of levamisole in the treatment of albino mice experimentally infected with Trypanosoma brucei brucei

Ijomanta

Ugochukwu

2016

J. Exper. Appl. Anim. Sci.

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“…Clearance time, relapse and survivability are acknowledged as principal pointers of trypanocide efficacy (Osondu et al, 2016;Aregawi et al, 2021). Thus, the shorter clearance time (4 days PT) observed in groups 3 and 4 rats against the group 6 rats (14 days PT) may be attributed to the fact that treatments were instituted at different periods and the level of parasitaemia varied in each infected group at the time of treatment, with group 6 which was treated at day 14 PI having the highest parasitaemia level.…”

Section: Discussio Discussio Discussio Discussion N N Nmentioning

confidence: 99%

Effect of time of treatment on the efficacy of trypanocides in rats experimentally infected with Trypanosoma brucei brucei

EZEH,

IHEAGWAM,

OBI

et al. 2023

Not Sci Biol

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The effect of treatment time on the efficacy of trypanocides in rats experimentally infected with Trypanosoma brucei brucei was assessed. The thirty albino rats utilized in this study were divided into six groups, each with five rats. Group 1 rats were uninfected while those in groups 2 - 6 were inoculated intraperitoneally with 106 trypanosomes. Group 2 rats were left untreated while groups 3 - 6 rats were treated respectively on days 5, 8, 11 and 14 post infection (PI) with 1.0 mg/kg Securidium® (brand of isometamidium chloride) intraperitoneally. Level of parasitaemia, rectal temperature, clinical signs, haematological indices (packed cell volume and total leucocyte count) and survivability were used to evaluate the treatment time on the efficacy of Securidium®. Pre-patent period was 4 - 5 days. On days 4, 5, and 11 following the treatments (PT), the parasites were eliminated in the treated groups 3 - 6 respectively. Also, two rats relapsed in group 3 from 37 days PT with 20% mortality, whereas groups 4 - 6 rats relapsed from days 19, 16 and 21 PT respectively. Groups 4 - 6 rats had 40%, 60% and 80% mortalities respectively. The mean PCV and TLC showed a striking drop (p<0.05) PI, however, group 3 had a better result PT compared to other infected-treated groups. In conclusion, it is safe to say that treatment time is a significant determinant of therapeutic efficacy in trypanosomosis, as early treatment group had better overall indices of therapeutic efficacy than the late treatment groups.

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“…Similarly, in this study, trypanocidal activity of ivermectin against T. evansi has been demonstrated IC 50 at 13.82 µM under in vitro conditions; however, the results under clinical condition still need to be investigated. So far, there are few preliminary random in vivo trials (at the dose rate of 200–400 µg/kg, intraperitoneally), without determining the in vitro efficacy, of ivermectin against kinetoplastid protozoan parasites (Dias et al 2005 ; Udensi and Fagbenro-Beyioku 2012 ; Osondu et al 2016 ). Additionally, the T. evansi is responsible for nervous sign in several animal host due to its capability to invade central nervous system of host; however, ivermectin is unable to invade the blood–brain barrier (Edwards 2003 ) and will certainly remain ineffective in cases showing the nervous sign due to trypanosomosis.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, the T. evansi is responsible for nervous sign in several animal host due to its capability to invade central nervous system of host; however, ivermectin is unable to invade the blood–brain barrier (Edwards 2003 ) and will certainly remain ineffective in cases showing the nervous sign due to trypanosomosis. Further, the T. evansi is nowadays considered as subspecies of T. brucei (Cuypers et al 2017 ; Oldrieve et al 2021 ) and the ivermectin was found ineffective to treat T. brucei infection in rats (Osondu et al 2016 ). Majority of these studies remain inconclusive in dearth of information regarding the effective dose required for trypanocidal activity of ivermectin.…”

Section: Discussionmentioning

confidence: 99%

“…In 2012, 300 μg/mL/kg dose of ivermectin was reported to increase the mean survival period of T. brucei brucei -infected mice from 5 to 12 days (Udensi and Fagbenro-Beyioku 2012 ). Later, it was reported that ivermectin has no chemotherapeutic effect against T. b. brucei infection in rats (Osondu et al 2016 ). Nowadays, several researchers classify T. evansi and T. equiperdum as the subspecies of T. brucei (Cuypers et al 2017 ; Oldrieve et al 2021 ).…”

Section: Introductionmentioning

confidence: 99%

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In vitro anti-trypanosomal effect of ivermectin on Trypanosoma evansi by targeting multiple metabolic pathways

Gupta

Vohra

Sethi

et al. 2022

Trop Anim Health Prod

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High cytotoxicity and increasing resistance reports of existing chemotherapeutic agents against T. evansi have raised the demand for novel, potent, and high therapeutic index molecules for the treatment of surra in animals. In this regard, repurposing approach of drug discovery has provided an opportunity to explore the therapeutic potential of existing drugs against new organism. With this objective, the macrocyclic lactone representative, ivermectin, has been investigated for the efficacy against T. evansi in the axenic culture medium. To elucidate the potential target of ivermectin in T. evansi , mRNA expression profile of 13 important drug target genes has been studied at 12, 24, and 48 h interval. In the in vitro growth inhibition assay, ivermectin inhibited T. evansi growth and multiplication significantly ( p < 0.001) with IC 50 values of 13.82 μM, indicating potent trypanocidal activity. Cytotoxicity assays on equine peripheral blood mononuclear cells (PBMCs) and Vero cell line showed that ivermectin affected the viability of cells with a half-maximal cytotoxic concentration (CC 50 ) at 17.48 and 22.05 μM, respectively. Data generated showed there was significant down-regulation of hexokinase ( p < 0.001), ESAG8 ( p < 0.001), aurora kinase ( p < 0.001), casein kinase 1 ( p < 0.001), topoisomerase II ( p < 0.001), calcium ATPase 1 ( p < 0.001), ribonucleotide reductase I ( p < 0.05), and ornithine decarboxylase ( p < 0.01). The mRNA expression of oligopeptidase B remains refractory to the exposure of the ivermectin. The arginine kinase 1 and ribonucleotide reductase II showed up-regulation on treatment with ivermectin. The ivermectin was found to affect glycolytic pathways, ATP-dependent calcium ATPase, cellular kinases, and other pathway involved in proliferation and maintenance of internal homeostasis of T. evansi. These data imply that intervention with alternate strategies like nano-formulation, nano-carriers, and nano-delivery or identification of ivermectin homologs with low cytotoxicity and high bioavailability can be explored in the future as an alternate treatment for surra in animals. Graphical abstract

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A comparative study of the chemotherapeutic effects of diminazene aceturate and Ivermectin on Trypanosoma brucei brucei infected rats

Cited by 3 publications

References 23 publications

Comparative effects of graded doses of diaminanzine ace-turate and fixed doses of levamisole in the treatment of albino mice experimentally infected with Trypanosoma brucei brucei

Comparative effects of graded doses of diaminanzine ace-turate and fixed doses of levamisole in the treatment of albino mice experimentally infected with Trypanosoma brucei brucei

Effect of time of treatment on the efficacy of trypanocides in rats experimentally infected with Trypanosoma brucei brucei

In vitro anti-trypanosomal effect of ivermectin on Trypanosoma evansi by targeting multiple metabolic pathways

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