Treatment of Cutaneous Balamuthia mandrillaris Infection With Diminazene Aceturate: A Report of 4 Cases. Four cases of cutaneous Balamuthia mandrillaris infection were treated with diminazene aceturate. One patient was cured with mainly monotherapy, 2 patients were cured with diminazene aceturate and excision, and 1 patient died of drug-induced liver damage. This is the first report of B . mandrillaris infection treated with diminazene aceturate.
Therapeutic effect of diminazene aceturate on parasitic blood fluke Schistosoma mansoni infection. Praziquantel is currently the only drug available to treat schistosomiasis, a disease of enormous public health significance caused by a blood fluke of the genus Diminazene, a drug approved by the FDA, has been successfully used to treat diseases caused by blood protozoan parasites . In this study, we evaluated the antiparasitic properties of diminazene against and in mice harboring either chronic or early infections. , we monitored phenotypic and tegumental changes as well as the effects of the drug on pairing and egg production. In mice infected with either adult (chronic infection) or immature (early infection) worms, diminazene was administered intraperitoneally (10 to 100 mg/kg
ACE2 activator diminazene aceturate reduces adiposity but preserves lean mass in young and old rats. The obesity epidemic is multi-generational and is particularly debilitating in the aging population, necessitating the use of pharmaceutical interventions. Recent evidence suggests that increasing the activity of the angiotensin converting enzyme-2 [ACE2]/angiotensin-(1-7)[Ang-(1-7)]/Mas receptor (MasR) axis in obese animal models leads to significant reductions in body weight. It was hypothesized that activation of ACE2 via diminazene aceturate (DIZE) will significantly reduce body weight of rats fed a high fat diet. Young and old (4 and 23 months, respectively) male Fisher 344 × Brown Norway rats were fed 60% high fat diet for one week, and subsequently given either 15 mg/kg/day DIZE s.c
Diminazene Aceturate Improves Cardiac Fibrosis and Diastolic Dysfunction in Rats with Kidney Disease. Angiotensin converting enzyme (ACE) 2 is a negative regulator of the renin angiotensin system (RAS) through its role to degrade angiotensin II. In rats with subtotal nephrectomy (STNx), adverse cardiac remodelling occurs despite elevated cardiac ACE2 activity. We hypothesised that diminazene
Comparative experimental studies on Trypanosoma isolates in mice and response to diminazene aceturate and isometamidium chloride treatment The current study was undertaken from December 2015 to May 2016 with the aim of determining and comparing the pathogenicity and response to diminazene aceturate (DA) and isometamidium chloride (ISM) treatment in experimentally infected mice with trypanosome
The small molecule drug diminazene aceturate inhibits liver injury and biliary fibrosis in mice There is no established medical therapy to treat biliary fibrosis resulting from chronic inflammation in the biliary tree. We have recently shown that liver-specific over-expression of angiotensin converting enzyme 2 (ACE2) of the renin angiotensin system (RAS) ameliorated liver fibrosis in mice . Diminazene aceturate (DIZE), a small molecule drug approved by the US Food and Drug Administration, which is used to treat human trypanosomiasis, has been shown to have antifibrotic properties by enhancing ACE2 activity. In this study we sought to determine the therapeutic potential of DIZE in biliary fibrosis using bile duct ligated and multiple drug resistant gene-2 knockout mice. Additionally, human
Drug quality analysis of isometamidium chloride hydrochloride and diminazene diaceturate used for the treatment of African animal trypanosomosis in West Africa Diminazene diaceturate (DA) and isometamidium chloride hydrochloride (ISM) are with homidium bromide, the main molecules used to treat African Animal Trypanosomosis (AAT). These drugs can be purchased from official suppliers but also from
Chemotherapeutic efficacies of a clofazimine and diminazene aceturate combination against piroplasm parasites and their AT-rich DNA-binding activity on Babesia bovis Recently, we reported that clofazimine (CF) has an anti-piroplasm activity, but it could not completely eliminate parasites in the host. The currently available anti-piroplasm drug, diminazene aceturate (DA), has sometimes been
Diminazene aceturate prevents nephropathy by increasing glomerular ACE2 and AT2 receptor expression in a rat model of type1 diabetes One of the protective actions of angiotensin converting enzyme-2 (ACE2) is the inactivation of angiotensin II. Expression and activity of ACE2 was reduced in glomeruli of diabetic patients and in animal models of diabetes. Recently the potential role of recombinant ACE2 administration in preventing diabetic nephropathy (DN) has been shown. Here we have tested the effects of the ACE2 activator, diminazene aceturate (DIZE), in a model of DN. Male Wistar rats were rendered diabetic using a single dose of streptozotocin (55 mg·kg , i.p.). After 4 weeks, diabetic animals were divided into experimental groups and treated with DIZE, at a low dose (5 mg·kg ·day
Trypanosomiasis challenge estimation using the diminazene aceturate (Berenil) index in Zebu in Gabon A longitudinal study was conducted within a cattle ranch in Gabon to determine the diminazene aceturate (Berenil) index (DAI) in a group of Zebu, raised under low tsetse density; this measure providing an assessment of trypanosomiasis risk. The objective was to evaluate the trypanosomiasis intramuscular injection of diminazene aceturate (8 mg/kg). Twenty-nine single infectious events were recorded and a DAI of 1.45 was calculated. Two trypanosome species were identified: Trypanosoma congolense (96.2%) and Trypanosoma vivax (3.8%). The mean PCV value of the infected animals was lower (26.6) compared to non-infected animals (32.0). This study shows that DAI may be a useful tool to assess
Simultaneous Determination and Stability Studies on Diminazene Diaceturate and Phenazone Using Developed Derivative Spectrophotometric Method This work presents UV first derivative spectrophotometry as a precise, accurate, and feasible method for simultaneous determination of diminazene diaceturate and phenazone in bulk and dosage forms. The absorbance values of diminazene diaceturate and phenazone aqueous mixture were obtained at 398 nm and 273 nm, respectively. The developed method was proved to be linear over the concentration ranges (2-10) g/mL and (2.496-12.48) g/mL for diminazene diaceturate and phenazone, respectively, with good correlation coefficients (not less than 0.997). The detection and quantitation limits were found to be (LOD = 0.63 and 0.48 g/mL; LOQ = 1.92 and 1.47 g/mL
Angiotensin converting enzyme 2 and diminazene: role in cardiovascular and blood pressure regulation. Angiotensin converting enzyme 2 (ACE2) is an important regulator of the renin-angiotensin system through actions to degrade angiotensin II. Loss of ACE2 can contribute to the development and progression of cardiovascular disease, and experimental studies have highlighted a beneficial role for novel therapeutic approaches that activate or replenish tissue ACE2. This review focuses on experimental studies that have used the off-target effects of the antitrypanosomal agent, diminazene aceturate (DIZE) to activate ACE2. In cardiovascular disease, activation of the classical renin-angiotensin system and depletion of ACE2 leads to pathophysiological changes. One approach to activate ACE2
Diminazene aceturate: an antibacterial agent for Shiga-toxin-producing Escherichia coli O157:H7 The aim of this study was to investigate the bacteriostatic and bactericidal effects of diminazene aceturate (DA) against five strains of pathogenic bacteria and two strains of nonpathogenic bacteria. The results showed that 5 μg/mL of DA suppressed the growth of pathogenic by as much as 77% compared
Angiotensin-converting enzyme 2 activator diminazene aceturate prevents lipopolysaccharide-induced inflammation by inhibiting MAPK and NF-κB pathways in human retinal pigment epithelium Retinal inflammation is a devastating pathological process in ocular diseases. Functional impairment of retinal pigment epithelium (RPE) is associated with inflammatory retinal diseases. Enhancing the protective axis namely ACE2/Ang-(1-7)/Mas by activation of ACE2 presents anti-inflammatory properties. We investigated whether diminazene aceturate (DIZE), an angiotensin-converting enzyme 2 (ACE2) activator, prevented lipopolysaccharide (LPS)-induced inflammatory response by activating the protective axis and whether the effect was mediated by inhibiting the mitogen-activated protein kinase (MAPK
PCR and microsatellite analysis of diminazene aceturate resistance of bovine trypanosomes correlated to knowledge, attitude and practice of livestock keepers in South-Western Ethiopia. African Animal Trypanosomosis is threatening the agricultural production and cattle breeding more severely than any other livestock disease in the continent, even more since the advent of drug resistance . A longitudinal study was conducted from November 2012 to May 2013 in the Ghibe valley to evaluate diminazene aceturate (DA) resistance and assess livestock owner's perception of trypanocidal drug use. Four Peasant Associations (PAs) were purposively selected and the cattle randomly sampled in each PAs. At the beginning of the study (t0), 106 bovines positive for trypanosomes by the haematocrit centrifugation
In vitro activity and in vivo efficacy of a combination therapy of diminazene and chloroquine against murine visceral leishmaniasis The present study evaluated the in vitro activity and in vivo efficacy of diminazene combined with chloroquine as a potential drug against Leishmania donovani. Amphotericin B was used as a positive control drug. In vitro activity involved incubation of various drug . The results indicated that the diminazene-chloroquine combination was at least nine times more efficacious than individual drugs in killing promastigotes in culture. The diminazene-chloroquine combination was safer (Ld50 = 0.03±0.04) than Amphotericin B (Ld50 = 0.02±0.01). Body weight in infected mice increased significantly (P = 0.0007) from day 7 to day 37 following infection (P = 0.026). However, body
Topical administration of diminazene aceturate decreases inflammation in endotoxin-induced uveitis Our previous study demonstrated that an intraperitoneal injection of Diminazene Aceturate (DIZE) attenuated uveitis by activating ocular angiotensin-converting enzyme 2 (ACE2). Here, we investigated the anti-inflammatory effects on the ocular anterior segment of a topical administration of a DIZE
Down-sizing of neuronal network activity and density of presynaptic terminals by pathological acidosis are efficiently prevented by Diminazene Aceturate. Local acidosis is associated with neuro-inflammation and can have significant effects in several neurological disorders, including multiple sclerosis, brain ischemia, spinal cord injury and epilepsy. Despite local acidosis has been implicated that acidosis affects network activity, down-sizing firing and bursting behaviors as well as amplitudes. Furthermore, a protracted acidosis reduced the number of presynaptic terminals, while it did not affect the postsynaptic compartment. Application of the diarylamidine Diminazene Aceturate (DA) during acidosis significantly reverted both the loss of neuronal firing and bursting and the reduction
Diminazene protects corpus cavernosum against hypercholesterolemia-induced injury. Angiotensin-converting enzyme 2 (ACE2) is a key enzyme of the renin angiotensin system, which breaks down angiotensin II and forms angiotensin-(1-7). In erectile tissues, it has been documented that angiotensin II contributes to the development of erectile dysfunction (ED), while treatment with angiotensin-(1-7 ) improves penile erection. However, the expression and function of ACE2 in erectile tissues have never been investigated. Here, we examined the expression of ACE2 in erectile tissues and its actions against hypercholesterolemia-induced corpus cavernosum (CC) injury. Hypercholesterolemic apolipoprotein E knockout (ApoE(-/-) ) mice, a well-known model of ED, were treated with diminazene aceturate (DIZE
Diminazene Aceturate Enhances Angiotensin-Converting Enzyme 2 Activity and Attenuates Ischemia-Induced Cardiac Pathophysiology. Angiotensin-converting enzyme 2 (ACE2) plays a critical role against myocardial infarction (MI). We hypothesized that activation of intrinsic ACE2 would be protective against ischemia-induced cardiac pathophysiology. Diminazene aceturate (DIZE), a small molecule ACE2