Diminazene Research Articles

Literature Study: Babesiosis in Dogs in The Period of 2013-2023

Background: Babesiosis is an infectious disease caused by Babesia spp. with tick vectors Rhipicephalus sanguineus and Dermacentor margniatus (a tick-borne disease). Babesiosis transmission occurs through tick bites or blood transfusions. Diagnostic techniques involve the microscopic examination of blood smears, hematology, blood chemistry, and PCR laboratory analysis. Purpose: To determine the clinical symptoms, confirmation of diagnosis, and therapy used for babesiosis conditions in dogs. Method: Analysis was conducted on 22 literature cases of babesiosis in dogs with a publication period of 2013-2023. The analysis was carried out using the descriptive analysis method, a problem-solving procedure that describes the condition of the subject or object based on facts, characteristics, and any relationships between the phenomena being investigated. Qualitative research methods were used to examine natural object conditions, as a key instrument. Data source sampling was done purposively, the data collection techniques were combined, the data analysis was either inductive or qualitative, and qualitative research results emphasize meaning. Result: Dog patients with babesiosis have the highest prevalence of clinical symptoms, namely anorexia (62.5%), vomiting (33.3%), pyrexia (54.16%) lethargy (45.83%), brownish urination (29.16%), and ectoparasite infestation (29.16%). Confirmation of the diagnosis carried out included the microscopic examination of blood smears (100%), hematology (91.66%), blood chemistry (41.66%), and Polymerase Chain Reaction (PCR) (20.83%). The therapeutic management used included 3 combinations of antibiotics in 7 cases (31.81%), combination therapy of 2 antibiotics and an antiparasitic in 3 cases (13.63%), and combination therapy of 1 antibiotic and antiparasitic in 3 cases (13.63%). Conclusion: Antiparasitic therapy that can be used is imidocarb dipropionate, which works by inhibiting inositol in the erythrocytes infected with Babesia spp. and diminazene aceturate, which works by disrupting parasite DNA synthesis.

An evaluation of African animal trypanosomiasis control strategies in remote communities of Eastern Zambia.

Communities living in African animal trypanosomiasis (AAT) endemic areas of Zambia use several control strategies to protect their livestock from the devastating effects of trypanosomiasis. Several studies have reported the effectiveness of trypanosomiasis control strategies based on retrospective data. In this study, we assessed incidence rates of AAT in cattle (n = 227) using a prospective cohort study comprising 4 treatment groups, i.e., Diminazene aceturate, Isometamidium chloride, Cyfluthrin pour-on and Cypermethrin treated targets. The study was conducted in Mambwe district in Eastern Zambia between February 2019 and March 2020. The endemic prevalence of AAT for each group was determined using ITS-PCR prior to application of treatments. High endemic trypanosome pre-treatment rates were found in all Groups (Diminazene aceturate (61%), Isometamidium chloride (48%), Cyfluthrin pour-on (87%) and Cypermethrin targets (72%)). The overall apparent prevalence for the Mambwe district was 67% (152/227) and true prevalence at 95%CI was 63–71%. Once treatments were implemented, 12 monthly follow-ups were conducted. The average monthly incidence rates without standardization recorded: Diminazene aceturate (67%) Isometamidium chloride (35%), Cyfluthrin pour-on (55%) and Cypermethrin targets (61%). Incidence rates were standardized considering the endemic level of disease for each Group and the average standardized monthly incidence rate in the Diminazene aceturate Group was 7%; the Isometamidium chloride Group −13%; the Cyfluthrin Group −26%; and the Cypermethrin target Group, −17%. All Groups showed a decrease in incidence of AAT over the period of the study with the Cyfluthrin group showing to be the most effective in reducing AAT incidence in cattle.

Study of mRNA expression of thirteen genes of Trypanosoma evansi in response to diminazene aceturate and isometamidium chloride

The monomorphic, non-cyclic, extracellular haemoprotozoan parasite, Trypanosoma evansi leads to Surra disease in domesticated animals. Currently, diminazene aceturate (DA) and isometamidium chloride (ISM) are the most used chemotherapeutic agents for the treatment of Surra in animals. There is still little knowledge on the anti- trypanosomal mechanism of action of DA and ISM. The work addresses a significant gap in the understanding of the anti-typanosomal mechanism of DA and ISM by investigating their effects on mRNA expression profiles of 13 genes of T. evansi. The half maximal inhibitory concentration (IC50) of DA and ISM for a pony isolate of T. evansi was estimated as 335.3 nM and 308.6 nM, respectively. Transcript analysis of DA and ISM exposed T. evansi population showed its effects on the metabolic machinery of T. evansi by down-regulating the mRNA expression of all the 13 targeted genes. However, ISM exposure did not affect mRNA expression of Expression site-associated genes 8 (ESAG8), oligopeptidase B and ornithine decarboxylase genes. The finding provides valuable insights into the molecular action of these drugs, which is crucial for developing more effective treatment of Surra disease. Further, comprehensive transcriptome and proteomic analysis could provide a deeper insight into precise molecular pathway of these medications against T. evansi.

The Effect of Oxytetracycline Administration on Tissue Disposition of Diminazene Aceturate in Apparently Healthy Sahel Goats

The Effect of Oxytetracycline Administration on Tissue Disposition of Diminazene Aceturate in Apparently Healthy Sahel Goats

Activation of ACE2/Ang-(1–7)/Mas axis improves cognitive dysfunction induced by isoflurane in mice via inhibiting oxidative stress

BackgroundLong-term inhalation anesthesia is known to be associated with postoperative cognitive dysfunction. Our previous studies have confirmed that oxidative stress damage contributes to its mechanistic connection. Angiotensin-converting enzyme 2 (ACE2)/Angiotensin-(1–7)/Mas axis plays a crucial role in balancing the classic Renin-Angiotensin System (RAS) and regulating oxidative stress. This research aims to investigate the involvement of the ACE2/Angiotensin-(1–7)/Mas axis in the development of cognitive impairment induced by long-term isoflurane anesthesia. Methods3-month-old male C57BL/6 mice were randomly assigned to four groups: Control + Vehicle (C + Veh), Anesthesia + Vehicle (A + Veh), Control + Diminazene aceturate (C + DIZE), and Anesthesia + Diminazene aceturate (A + DIZE). Long-term isoflurane exposure was utilized to induce cognitive impairment. DIZE was administered intraperitoneally to mice 10 days prior to anesthesia to intervene ACE2. Cognitive function was administered using Y-maze and fear conditioning test. Flow Cytometry was used to measure the levels of ROS. Western blot was used to determine the expression levels of ACE2 and Mas, as well as the cognitive proteins such as phosphorylated N-methyl-D-aspartate receptor subtype 2B (p-NR2B) and Brain-Derived Neurotrophic Factor (BDNF). ResultsWe successfully constructed a long-term isoflurane anesthesia-mediated cognitive dysfunction model. Following long-term isoflurane anesthesia, there was a decrease in the levels of ACE2 and Mas in the hippocampus, accompanied by increased oxidative stress and significant cognitive impairment. Treatment with the ACE2 activator DIZE effectively restored the levels of ACE2 and Mas and decreased the content of ROS. Notably, DIZE treatment ameliorated cognitive dysfunction induced by long-term isoflurane exposure. ConclusionsThe findings suggest that the activation of the ACE2/Ang-(1–7)/Mas axis could reduce oxidative stress and improve cognitive impairment. ACE2/Ang-(1–7)/Mas axis may play a prophylactic role in mitigating isoflurane-induced cognitive decline and other cognitive impairments related to oxidative stress.

Trypanocide Use and Molecular Characterization of Trypanosomes Resistant to Diminazene Aceturate in Cattle in Northern Côte D'Ivoire.

The resistance of trypanosomes to the doses of trypanocide administered by farmers to their animals acts as a real brake on efforts to control to combat African trypanosomiasis. Thus, in-depth knowledge of the use of these different molecules and their resistance profiles will be necessary to establish an integrated strategy to combat African trypanosomiasis. To achieve these objectives, a participatory survey among farmers and a resistance diagnosis of trypanosome strains identified in three regions of northern Côte d'Ivoire (Bagoué, Poro and Tchologo) was carried out using the PCR-RFLP technique, followed by sequencing of genes of interest. This study made it possible to identify three molecules that are commonly used by 85% (63/74) of farmers. In descending order of use, we identified Isometamidium chloride (43%), Diminazene aceturate (28%) and Homidium bromide (14%). Three species of trypanosomes, Trypanosoma congolense, Trypanosoma. theileri and Trypanosoma vivax, were identified in farms, and only one strain had the adenosine transporter gene (Trypanosoma congolense), but this strain was sensitive to the Diminazene aceturate molecule. Comparison of the sequence of this trypanosome strain showed that it is different to the Kenyan strain diagnosed as resistant to the Diminazene aceturate molecule. This study shows that a variety of trypanocides are used by farmers, and that the resistance profile of the strains to the Diminazene aceturate molecule could not be observed. However, it is important to further investigate the other molecules encountered in Côte d'Ivoire.

Quality, supply chain, and use of Trypanocidal drugs among camel keepers in north-eastern Kenya: A cross-sectional study

The non-cyclic trypanosomiasis (surra), caused by Trypanosoma evansi, and mechanically transmitted by biting flies, hinders camel productivity in Kenya. Trypanocides are the most commonly used drugs to control surra. However, emergence of drug resistance by the parasites is a major limitation to control efforts. There is limited information on the quality of trypanocides, the supply chain and drug-use practices among camel keepers potentially contributing to development of drug resistance in Kenya. We sought to fill this gap by conducting a cross-sectional study among camel keepers in Isiolo and Marsabit counties, Kenya. We mapped the trypanocide drugs supply chain through quantitative and qualitative surveys. We administered a semi-structured questionnaire to camel keepers to generate data on trypanocides-use practices, including the types, sources, person who administers treatment, reconstitution, dosage, route and frequency of administration, among others. Additionally, we tested the quality of trypanocidal drugs retailed in the region. We mapped a total of 55 and 49 agro-veterinary outlets and general (ordinary) shops retailing veterinary drugs in the two counties, respectively. These comprised of 29 and 26 agro-veterinary outlets, as well as 24 and 25 general shops in Isiolo and Marsabit counties, respectively. Overall, the respondents experienced 283 surra cases in the three-month recall period, which were treated with trypanocides. The majority of these cases were diagnosed by camel owners (71.7%) and herders (24.1%). A significant proportion of the cases were treated by camel owners (54.8%), herders (35.3%), the owner's son (3.2%) and veterinary personnel (1.1%) (χ2 = 24.99, p = 0.000). Most of the households sourced the drugs from agro-veterinary outlets (59.0%), followed by general shops (19.8%), veterinary personnel (2.1%), and open-air markets (0.4%) (χ2 = 319.24, p = 0.000). Quinapyramine was the most (56.9%) predominantly used trypanocide in treatment of surra, followed by homidium (19.8%), isometamidium (15.9%), diminazene aceturate (6.7%), and ethidium (0.7%) (χ2 = 340.75, p < 0.000). Only a meager proportion of respondents (15.2%) used the drugs correctly as instructed by the manufacturers. We recorded an association between correct drug usage, with the person who administers the treatment (χ2 = 17.7, p = 0.003), and the type of trypanocide used (χ2 = 19.4, p < 0.001). All the drug samples tested had correct concentrations of active ingredient (100.0%), and therefore of good quality. We have demonstrated that whereas the trypanocides retailed in the region by authorized vendors are of good quality, there is widespread incorrect handling and use of the drugs by unqualified individuals, which may contribute to treatment failure and emergence of trypanocide resistance.

Activation of angiotensin converting enzyme 2 promotes hippocampal neurogenesis via activation of Wnt/β-catenin signaling in hypertension

Hypertension-induced brain renin-angiotensin system (RAS) activation and neuroinflammation are hallmark neuropathological features of neurodegenerative diseases. Previous studies from our lab have shown that inhibition of ACE/Ang II/AT1R axis (by AT1R blockers or ACE inhibitors) reduced neuroinflammation and accompanied neurodegeneration via up-regulating adult hippocampal neurogenesis. Apart from this conventional axis, another axis of RAS also exists i.e., ACE2/Ang (1–7)/MasR axis, reported as an anti-hypertensive and anti-inflammatory. However, the role of this axis has not been explored in hypertension-induced glial activation and hippocampal neurogenesis in rat models of hypertension. Hence, in the present study, we examined the effect of ACE2 activator, Diminazene aceturate (DIZE) at 2 different doses of 10 mg/kg (non-antihypertensive) and 15 mg/kg (antihypertensive dose) in renovascular hypertensive rats to explore whether their effect on glial activation, neuroinflammation, and neurogenesis is either influenced by blood-pressure. The results of our study revealed that hypertension induced significant glial activation (astrocyte and microglial), neuroinflammation, and impaired hippocampal neurogenesis. However, ACE2 activation by DIZE, even at the low dose prevented these hypertension-induced changes in the brain. Mechanistically, ACE2 activation inhibited Ang II levels, TRAF6-NFκB mediated inflammatory signaling, NOX4-mediated ROS generation, and mitochondrial dysfunction by upregulating ACE2/Ang (1–7)/MasR signaling. Moreover, DIZE-induced activation of the ACE2/Ang (1–7)/MasR axis upregulated Wnt/β-catenin signaling, promoting hippocampal neurogenesis during the hypertensive state. Therefore, our study demonstrates that ACE2 activation can effectively prevent glial activation and enhance hippocampal neurogenesis in hypertensive conditions, regardless of its blood pressure-lowering effects.

Effect of Diminazene Aceturate, an ACE2 activator, on platelet CD40L signaling induced glial activation in rat model of hypertension

Hypertension causes platelet activation and adhesion in the brain resulting in glial activation and neuroinflammation. Further, activation of Angiotensin-Converting Enzyme 2/Angiotensin (1–7)/Mas Receptor (ACE2/Ang (1–7)/MasR) axis of central Renin-Angiotensin System (RAS), is known to reduce glial activation and neuroinflammation, thereby exhibiting anti-hypertensive and anti-neuroinflammatory properties. Therefore, in the present study, the role of ACE2/Ang (1–7)/MasR axis was studied on platelet-induced glial activation and neuroinflammation using Diminazene Aceturate (DIZE), an ACE2 activator, in astrocytes and microglial cells as well as in rat model of hypertension. We found that the ACE2 activator DIZE, independently of its BP-lowering properties, efficiently prevented hypertension-induced glial activation, neuroinflammation, and platelet CD40-CD40L signaling via upregulation of ACE2/Ang (1–7)/MasR axis. Further, DIZE decreased platelet deposition in the brain by reducing the expression of adhesion molecules on the brain endothelium. Activation of ACE2 also reduced hypertension-induced endothelial dysfunction by increasing eNOS bioavailability. Interestingly, platelets isolated from hypertensive rats or activated with ADP had significantly increased sCD40L levels and induced significantly more glial activation than platelets from DIZE treated group. Therefore, injection of DIZE pre-treated ADP-activated platelets into normotensive rats strongly reduced glial activation compared to ADP-treated platelets. Moreover, CD40L-induced glial activation, CD40 expression, and NFкB-NLRP3 inflammatory signaling are reversed by DIZE. Furthermore, the beneficial effects of ACE2 activation, DIZE was found to be significantly blocked by MLN4760 (ACE2 inhibitor) as well as A779 (MasR antagonist) treatments. Hence, our study demonstrated that ACE2 activation reduced the platelet CD40-CD40L induced glial activation and neuroinflammation, hence imparted neuroprotection.

Diminazene aceturate inhibits the SARS-CoV-2 spike protein-induced inflammation involving leukocyte migration and DNA extracellular traps formation

AimsTo investigate the SARS-CoV-2 Spike protein (Spk)-induced inflammatory response and its downmodulation by diminazene aceturate (DIZE). Materials and methodsThrough inducing Spk inflammation in murine models, leukocyte migration to the peritoneum, levels of myeloperoxidase (MPO), malondialdehyde (MDA), rolling and adhesion of mesenteric leukocytes, and vascular permeability were investigated. Extracellular DNA traps (DETs) induced by Spk and the production of IL-6 and TNF-α were analyzed using human neutrophils, monocytes, and macrophages. In silico assays assessed the molecular interaction between DIZE and molecules related to leukocyte migration and DETs induction. Key findingsSpk triggered acute inflammation, demonstrated by increasing leukocyte migration. Oxidative stress was evidenced by elevated levels of MPO and MDA in the peritoneal liquid. DIZE attenuated cell migration, rolling, and leukocyte adhesion, improved vascular barrier function, mitigated DETs, and reduced the production of Spk-induced pro-inflammatory cytokines. Computational studies supported our findings, showing the molecular interaction of DIZE with targets such as β2 integrin, PI3K, and PAD2 due to its intermolecular coupling. SignificanceOur results outline a novel role of DIZE as a potential therapeutic agent for mitigating Spk-induced inflammation.

Diminazene aceturate attenuates systemic inflammation via microbiota gut-5-HT brain-spleen sympathetic axis in male mice

The sympathetic arm of the inflammatory reflex is the efferent pathway through which the central nervous system (CNS) can control peripheral immune responses. Diminazene aceturate (DIZE) is an antiparasitic drug that has been reported to exert protective effects on various experimental models of inflammation. However, the pathways by which DIZE promotes a protective immunomodulatory effects still need to be well established, and no studies demonstrate the capacity of DIZE to modulate a neural reflex to control inflammation. C57BL/6 male mice received intraperitoneal administration of DIZE (2 mg/Kg) followed by lipopolysaccharide (LPS, 5 mg/Kg, i.p.). Endotoxemic animals showed hyperresponsiveness to inflammatory signals, while those treated with DIZE promoted the activation of the inflammatory reflex to attenuate the inflammatory response during endotoxemia. The unilateral cervical vagotomy did not affect the anti-inflammatory effect of DIZE in the spleen and serum. At the same time, splenic denervation attenuated tumor necrosis factor (TNF) synthesis in the spleen and serum. Using broad-spectrum antibiotics for two weeks showed that LPS modulated the microbiota to induce a pro-inflammatory profile in the intestine and reduced the serum concentration of tryptophan and serotonin (5-HT), while DIZE restored serum tryptophan and increased the hypothalamic 5-HT levels. Furthermore, the treatment with 4-Chloro-DL-phenylalanine (pcpa, an inhibitor of 5-HT synthesis) abolished the anti-inflammatory effects of the DIZE in the spleen. Our results indicate that DIZE promotes microbiota modulation to increase central 5-HT levels and activates the efferent sympathetic arm of the inflammatory reflex to control splenic TNF production in endotoxemic mice.

Immunomodulatory potential of Sarcophaga argyostoma larval hemolymph as a natural alternative to berenil in treating Trypanosoma evansi in vivo

This study compared effects of diminazene aceturate (berenil), commonly used to treat domestic animals infected with Trypanosoma evansi, with the hemolymph of Sarcophaga argyostoma larva. The hemolymph may be acting as a possible natural alternative to berenil, based on immunomodulation mediated inflammatory response. Inflammatory mediators and histopathological changes in liver, kidney, and spleen of albino mice experimentally infected with T. evansi were studied. Mice were divided into five groups: G1, uninfected, untreated (negative control); G2, T. evansi infected (positive control); G3, infected and treated with berenil; G4, infected and treated with hemolymph; G5, infected and treated with hemolymph 3 days before infection (prophylactic group). Animals in (G4) and (G5) exhibited a significant overall reduction in serum levels of IFN-γ. However, the reduction in TNF-α and IL-6 levels was more limited compared to (G2) and (G3). Notably, an elevation in IL-10 levels was observed compared to animals in other groups. Furthermore, the groups treated with hemolymph demonstrated an alleviation of T. evansi infection in contrast to the other groups. This study highlights that the administration of Sarcophaga argyostoma larval hemolymph at a dosage of 0.5 ml/kg significantly inhibited T. evansi organisms in vivo, showcasing a pronounced trypanocidal effect.

Inhibition of SAT1 alleviates chondrocyte inflammation and ferroptosis by repressing ALOX15 expression and activating the Nrf2 pathway.

Osteoarthritis (OA) is the most common chronic pathema of human joints. The pathogenesis is complex, involving physiological and mechanical factors. In previous studies, we found that ferroptosis is intimately related to OA, while the role of Sat1 in chondrocyte ferroptosis and OA, as well as the underlying mechanism, remains unclear. In this study, interleukin-1β (IL-1β) was used to simulate inflammation and Erastin was used to simulate ferroptosis in vitro. We used small interfering RNA (siRNA) to knock down the spermidine/spermine N1-acetyltransferase 1 (Sat1) and arachidonate 15-lipoxygenase (Alox15), and examined damage-associated events including inflammation, ferroptosis, and oxidative stress of chondrocytes. In addition, a destabilization of the medial meniscus (DMM) mouse model of OA induced by surgery was established to investigate the role of Sat1 inhibition in OA progression. The results showed that inhibition of Sat1 expression can reduce inflammation, ferroptosis changes, reactive oxygen species (ROS) level, and lipid-ROS accumulation induced by IL-1β and Erastin. Knockdown of Sat1 promotes nuclear factor-E2-related factor 2 (Nrf2) signalling. Additionally, knockdown Alox15 can alleviate the inflammation-related protein expression induced by IL-1β and ferroptosis-related protein expression induced by Erastin. Furthermore, knockdown Nrf2 can reverse these protein expression alterations. Finally, intra-articular injection of diminazene aceturate (DA), an inhibitor of Sat1, enhanced type II collagen (collagen II) and increased Sat1 and Alox15 expression. Our results demonstrate that inhibition of Sat1 could alleviate chondrocyte ferroptosis and inflammation by downregulating Alox15 activating the Nrf2 system, and delaying the progression of OA. These findings suggest that Sat1 provides a new approach for studying and treating OA.

Pyronaridine combined with diminazene aceturate inhibits Babesia in vitro and in vivo

Objective: To evaluate the combination therapy of pyronaridine tetraphosphate and diminazene aceturate against Babesia in vitro and in vivo. Methods: Bioinformatic analysis was performed using atom pair fingerprints. An in vitro combination test was performed against Babesia bovis and Theileria equi. Moreover, the in vivo chemotherapeutic efficacy of pyronaridine tetraphosphate in combination with diminazene aceturate was investigated against the growth of Babesia microti in mice using a fluorescence inhibitory assay. Results: Pyronaridine tetraphosphate and diminazene aceturate exhibited nearly similar molecular weights. The in vitro combination of pyronaridine tetraphosphate and diminazene aceturate was synergistic on Babesia bovis and additive on Theileria equi. In addition, 5 mg/kg pyronaridine tetraphosphate combined with 10 mg/kg diminazene aceturate inhibited Babesia microti growth significantly compared with those observed after treatment with 25 mg/kg diminazene aceturate alone from day 6 post treatment to day 12 post treatment. The combination therapy also normalized the hematological parameters of infected mice. Conclusions: An oral dose of pyronaridine tetraphosphate combined with a subcutaneous dose of diminazene aceturate inhibits Babesia in vitro and in mice, suggesting it might be a new paradigm for the treatment of babesiosis.

Daflon 500 mg alone and its combination with diminazene aceturate inhibits alterations in lipid profile induced by Trypanosoma brucei brucei infection in Wistar rats

The effect of Daflon® 500 mg (DF) and Diminazene aceturate (DZ) on the lipid profile of adult male Wistar rats infected with T. brucei brucei were investigated for their use in trypanosomosis. Fifty adult male Wistar rats were randomly divided into 5 groups of 10 rats each. Group I rats were treated with distilled water (1 mL/kg) per os, while group II rats were 6 intraperitoneally infected with T. brucei brucei (10 trypanosomes/mL of blood). Group III 6 rats were infected with T. brucei brucei (10 trypanosomes/mL of blood) and intraperitoneally administered with DZ at 3.5 mg/kg once, when infection was established. Groups IV and Vwere first pretreated with DF at 100 mg/kg per os for three weeks, followed 6 by infection with T. brucei brucei (10 trypanosomes/mL of blood) intraperitoneally. Treatment with DF continued for another one week. In addition, group V rats were intraperitoneally administered with DZ at 3.5 mg/kg once, when infection was established prior to continuation with DF for another one week. Pretreatment with DF alone or in combination with DZ decreased parasitaemia, lowered triglyceride level and significantly (P &lt; 0.05) decreased cholesterol and low-density lipoprotein concentrations in T. brucei ® brucei-infected Wistar rats. In conclusion, daflon 500 mg alone or in combination with diminazene aceturate may be beneficial in the treatment of the infection in Wistar rats. L'effet du Daflon® 500 mg (DF) et de l'acéturate de diminazène (DZ) sur le profil lipidique de rats Wistar mâles adultes infectés par T. brucei brucei a été étudié pour leur utilisation dans la trypanosomose. Cinquante rats Wistar mâles adultes ont été répartis au hasard en 5 groupes de 10 rats chacun. Les rats du groupe I ont été traités avec de l'eau distillée (1 mL/kg) per os, tandis que les rats du groupe II ont été infectés par voie intrapéritonéale avec T. brucei brucei (106 trypanosomes/mLde sang). Les rats du groupe III ont été infectés par T. brucei brucei (106 trypanosomes/mL de sang) et administrés par voie intrapéritonéale avecdu DZ à raison de 3,5 mg/kg une fois, lorsque l'infection était établie. Les groupes IVet Vont d'abord été prétraités avec DF à 100 mg/kg per os pendant trois semaines, suivi d'une infection par T. brucei brucei (106 trypanosomes/mL de sang) par voie intrapéritonéale. Le traitement par DF s'est poursuivi pendant encore une semaine. De plus, des rats du groupe V ont reçu une administration intrapéritonéale de DZ à raison de 3,5 mg/kg une fois, lorsque l'infection était établie avant la poursuite du traitement par DF pendant une semaine supplémentaire. Le prétraitement avec DF seul ou en association avec DZ a diminué la parasitémie, abaissé le taux de triglycérides et significativement (P &lt; 0,05) diminué les concentrations de cholestérol et de lipoprotéines de basse densité chez les rats Wistar infectés par T. brucei brucei. En conclusion, le daflon® 500 mg seul ou en association avec l'acéturate de diminazène pourrait être bénéfique dans le traitement de l'infection chez le rat Wistar

Blood Transfusion as an Adjunct Therapy in a Foal Affected with Trypanosomiasis

Trypanosomiasis is an infectious haemo protozoan disease that affects various domestic, pet, and wild animals. A 9-month-old foal was presented to the Veterinary Clinical Complex of the College of Veterinary Science, Rajendranagar, Hyderabad with a complaint of reduced appetite, red color urine, and rapid loss of weight for a week. Upon physical examination pale conjunctival and buccal mucous membranes were noticed along with a temperature of 97.20 F Auscultation of the heart revealed high intensity heart beats with 72 bpm. A blood smear was prepared from peripheral veins and its examination revealed RBCs with pleomorphism, microcytes and a few RBCs are acanthocytes. Wet film examination revealed vigorously moving spindle-shaped intercellular parasites Further, Giemsa-stain smear examination revealed the presence of intercellular spindle-shaped organisms, which are suggestive of Trypanosoma evansi. A complete blood picture revealed severe anemia, low levels of hemoglobin, and thrombocytosis, monocytosis, and lymphocytosis. Based on these findings, the case was diagnosed as trypanosomosis and the treatment was initiated with Diminazene aceturate at 3.5mg/K, iron Folic acid, and cyanocobalamin, along with blood transfusion to manage anemia. The foal was successfully revived following a blood transfusion.

Cardioprotective effects of losartan and diminazene against the ischemia/reperfusion injury in hyperthyroidism rats.

Hyperthyroidism is a condition where the thyroid gland produces high levels of thyroid hormone. Heart diseases are one of the main complications of hyperthyroidism. Several studies have shown that losartan (LOS) and diminazene aceturate (DIZE) possess cardioprotection effects against cardiac hypertrophy, ischemic heart disease, and heart failure. The research aimed to investigate the cardioprotection of LOS, DIZE, and their combination in the case of levothyroxine (LT4)-induced cardiomyopathy in rats. Hyperthyroidism was induced by LT4 in drinking water (12mg/L) for 28 days. LOS (10mg/kg, orally) and/or DIZE (15mg/kg, subcutaneously) were administrated in rats with hyperthyroidism for 28 days. Decreased serum creatine kinase myoglobin and lactate dehydrogenase levels and cardiac hypertrophy by DIZE and combination therapy in hyperthyroidism rats have been reported. Cardiac hemodynamic findings showed that DIZE and its combination with LOS decreased the LT4-mediated left ventricular developed pressure (LVDP), rate pressure product (RPP), and RPP recovery percentage. Elevated cardiac oxidative stress and inflammation were confirmed by decreasing cardiac superoxide dismutase (SOD) activity and increasing the total oxidative stress and tumor necrosis factor-alpha (TNF-α) levels. SOD activity and TNF-α level were reversed by LOS and DIZE administration, respectively. Generally, DIZE and combination therapy with LOS improved cardiac dysfunction caused by hyperthyroidism in rats, whereas LOS alone has not been able to effectively respond to this dysfunction.

In vitro and in vivo antitrypanosomal activity of the fresh leaves of Ranunculus Multifidus Forsk and its major compound anemonin against Trypanosoma congolense field isolate

BackgroundAnimal trypanosomiasis is a major livestock problem due to its socioeconomic impacts in tropical countries. Currently used trypanocides are toxic, expensive, and the parasites have developed resistance to the existing drugs, which calls for an urgent need of new effective and safe chemotherapeutic agents from alternative sources such as medicinal plants. In Ethiopian traditional medicine fresh leaves of Ranunculus multifidus Forsk, are used for the treatment of animal trypanosomiasis. The present study aimed to evaluate the antitrypanosomal activity of the fresh leaves of R. multifidus and its major compound anemonin against Trypanosoma congolense field isolate.MethodsFresh leaves of R. multifidus were extracted by maceration with 80% methanol and hydro-distillation to obtain the corresponding extracts. Anemonin was isolated from the hydro-distilled extract by preparative TLC. For the in vitro assay, 0.1, 0.4, 2 and 4 mg/ml of the test substances were incubated with parasites and cessation or drop in motility of the parasites was monitored for a total duration of 1 h. In the in vivo assay, the test substances were administered intraperitoneally daily for 7 days to mice infected with Trypanosoma congolense. Diminazene aceturate and 1% dimethylsulfoxide (DMSO) were used as positive and negative controls, respectively.ResultsBoth extracts showed antitrypanosomal activity although the hydro-distilled extract demonstrated superior activity compared to the hydroalcoholic extract. At a concentration of 4 mg/ml, the hydro-distilled extract drastically reduced motility of trypanosomes within 20 min. Similarly, anemonin at the same concentration completely immobilized trypanosomes within 5 min of incubation, while diminazene aceturate (28.00 mg/kg/day) immobilized the parasites within 10 min. In the in vivo antitrypanosomal assay, anemonin eliminates parasites at all the tested doses (8.75, 17.00 and 35.00 mg/kg/day) and prevented relapse, while in diminazene aceturate-treated mice the parasites reappeared on days 12 to 14.ConclusionsThe current study demonstrated that the fresh leaves of R. multifidus possess genuine antitrypanosomal activity supporting the use of the plant for the treatment of animal trypanosomiasis in traditional medicine. Furthermore, anemonin appears to be responsible for the activity suggesting its potential as a scaffold for the development of safe and cost effective antitrypanosomal agent.

Evaluating the influence of Trypanosomiasis on murine model using Corchorus olitorius leaf extract as a trypanocidal agent

Trypanosomiasis, a parasitic disease caused by trypanosomes, which are flagellate protozoa transmitted through the bite of the tsetse fly, manifests with symptoms including substantial weight loss, anemia, fever, edema, adenitis, dermatitis, and nervous disorders. This research investigated the impact of trypanosomiasis on a murine model while utilizing Corchorus olitorius leaf extract as a potential trypanocidal agent. An acute toxicity analysis was conducted following Lorke's method, and the antitrypanosomal efficacy was assessed in rats at doses of 100, 200, and 400 mg/kg over three weeks, monitoring changes in parasitemia count, body weight, and hematological parameters. Additionally, lipid profile, electrolyte concentration, and liver and kidney function were evaluated using standard techniques. The extract demonstrated potent antitrypanosomal activity at 400 mg/kg, significantly reducing the parasitemia count to 11.33±4.16 count/mL compared to the positive control at 2.5 mg/kg body weight doses. Furthermore, the 400 mg/kg dose notably increased packed cell volume and body weight in infected rats. Moreover, there were no significant discrepancies in numerous hematological parameters between the infected treated with diminazene aceturate and the extract's 400 mg/kg body weight. This study suggests that Corchorus olitorius extract exhibits significant antitrypanosomal, antilipidemic, and erythropoietic effects, mitigating parasitemia count, lipid levels, and oxidative damage by impeding the biochemical activities of trypanosomes through its active constituents. Thus, Corchorus olitorius extract may offer an alternative therapeutic approach for managing trypanosomal infections.

Comparison of the Therapeutic Efficacy of Diminazene Aceturate and ‎Isometamidium Chloride in Local Dogs Experimentally Infected ‎with Trypanosoma brucei

The chemotherapeutic efficacy of diminazene aceturate (DA) and isometamidium chloride (IMC) were compared in dogs experimentally infected with Trypanosoma brucei. Twenty Nigerian local breeds of dogs were used for the study. They were divided into four groups of five dogs each. Dogs in group I served as uninfected untreated control, group II was infected untreated, while groups III and IV were the infected treated with DA and IMC respectively. Administration of DA and IMC effectively cleared the parasites from the blood stream of the treated dogs. However, the infection subsequently relapsed at days 28 and 49 post treatment (pt) in DA and IMC treated groups, respectively. The red cell parameters (PCV, HB, and RBC) decreased significantly (P&lt;0.05) following infection. They were significantly (P &lt; 0.05) higher in IMC treated group than the DA treated group comparable with the control. The infected groups had elevated total white blood cell counts. However, the DA treated, and IMC treated groups did not show any significant (P&gt; 0.05) difference when compared together with the control. The mean activities of SAP, AST, and ALT increased significantly (P&lt;0.05) in the infected groups compared with the control. The mean blood urea nitrogen (BUN) increased significantly (P&lt;0.05) on days 21 and 28 post infection (pi) in the infected untreated group and IMC treated groups. The mean creatinine(CRT) was significantly (P&lt;0.05) higher in all the infected groups on day 14 pi compared to the control. From day 35 pi the mean BUN and CRT levels returned to normal values. It was thus concluded from this study that IMC exhibited more chemotherapeutic therapeutic activity over DA, as evidenced from the result of relapsed infections post treatment and haematological changes. However, the serum biochemical parameters were significantly altered in both DA and IMC treated groups compared to the control.