Diminazene Aceturate (Berenil) Modulates the Host Cellular and Inflammatory Responses to Trypanosoma congolense Infection

Kuriakose, Shiby; Muleme, Helen M.; Onyilagha, Chukwunonso; Singh, R. V.; Jia, Ping; Uzonna, Jude E.

doi:10.1371/journal.pone.0048696

Cited by 68 publications

(67 citation statements)

References 28 publications

(49 reference statements)

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“…The compound was also shown to interfere with the mitochondrial membrane potential (Lanteri et al 2008). Interestingly, it has been suggested that diminazene can also modulate the host immune response by dampening pro-inflammatory cytokines and excessive immune activation, which might also influence the in vivo effects of the drug (Kuriakose et al 2012). …”

Section: Veterinary Trypanocides: Dosage Pharmacokinetics Mode Of Amentioning

confidence: 99%

The animal trypanosomiases and their chemotherapy: a review

et al. 2016

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SUMMARYPathogenic animal trypanosomes affecting livestock have represented a major constraint to agricultural development in Africa for centuries, and their negative economic impact is increasing in South America and Asia. Chemotherapy and chemoprophylaxis represent the main means of control. However, research into new trypanocides has remained inadequate for decades, leading to a situation where the few compounds available are losing efficacy due to the emergence of drug-resistant parasites. In this review, we provide a comprehensive overview of the current options available for the treatment and prophylaxis of the animal trypanosomiases, with a special focus on the problem of resistance. The key issues surrounding the main economically important animal trypanosome species and the diseases they cause are also presented. As new investment becomes available to develop improved tools to control the animal trypanosomiases, we stress that efforts should be directed towards a better understanding of the biology of the relevant parasite species and strains, to identify new drug targets and interrogate resistance mechanisms.

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Section: Veterinary Trypanocides: Dosage Pharmacokinetics Mode Of Amentioning

confidence: 99%

The animal trypanosomiases and their chemotherapy: a review

et al. 2016

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“…Kupffer cells were isolated 24 hour after injury as described by Kuriakose et al (18) with minor modifications. Rinsed liver tissue was incubated at 37°C for 30 minutes in collagenase IV (5000 CDU/mL), run through a gentleMACS Dissociator (Miltenyi Biotec, Auburn, CA), and passed through a sterile 100 um strainer into phosphate-buffered saline (Miltenyi Biotec, Auburn, CA) containing 0.5% bovine serum albumin.…”

Section: Methodsmentioning

confidence: 99%

“…CD11b + cells were enriched by positive selection using AUTOMACS (Miltenyi Biotec Auburn, CA). Enriched liver CD11b + cells isolated by this method have been shown to be greater than 96% positive for F4/80 expression as assessed by flow cytometry (18). …”

Section: Methodsmentioning

confidence: 99%

Kupffer Cell p38 Mitogen-Activated Protein Kinase Signaling Drives Postburn Hepatic Damage and Pulmonary Inflammation When Alcohol Intoxication Precedes Burn Injury

Chen

O'Halloran

Shults

et al. 2016

Critical Care Medicine

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Objective Clinical and animal studies demonstrate that alcohol intoxication at the time of injury worsens post-burn outcome. The purpose of this study was to determine the role and mechanism of Kupffer cell derangement in exacerbating post-burn end organ damage in alcohol exposed mice. Design Interventional study. Setting Research Institute. Subjects Male C57BL/6 mice. Interventions Alcohol administered 30 minutes before a 15% scald burn injury. Antecedent Kupffer cell depletion with clodronate liposomes (0.5 mg/kg). p38 mitogen-activated protein kinase (MAPK) inhibition via SB203580 (10 mg/kg). Measurements and Main Results Kupffer cells were isolated 24 hours after injury and analyzed for p38 activity and IL-6 production. Intoxicated burned mice demonstrated a 2-fold (p<0.05) elevation of Kupffer cell p38 activation relative to either insult alone and this corresponded to a 43% (p<0.05) increase in IL-6 production. Depletion of Kupffer cells attenuated hepatic damage as seen by decreases of 53% (p<0.05) in serum ALT and 74% (p<0.05) in hepatic triglycerides, as well as a 77% reduction (p<0.05) in serum IL-6 levels compared to matched controls. This mitigation of hepatic damage was associated with a 54% decrease (p<0.05) in pulmonary neutrophil infiltration and reduced alveolar wall thickening by 45% (p<0.05). In vivo p38 inhibition conferred nearly identical hepatic and pulmonary protection after the combined injury as mice depleted of Kupffer cells. Conclusions Intoxication exacerbates post-burn hepatic damage through p38-dependent IL-6 production in Kupffer cells.

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“…African trypanosomosis is a disease of humans and livestock caused by several species of flagellated singlecelled protozoan parasites belonging to the genus Trypanosoma (Kuriasko et al, 2012). Trypanosomosis is *Corresponding author.…”

Section: Introductionmentioning

confidence: 99%

Ex vivo trypanostatic effect of stem-bark extracts of Securidaca longipedunculata (Fres. Holl) against Trypanosoma brucei brucei

Tauheed¹,

Сулейман²,

Mamman³

et al. 2016

Afr. J. Biotechnol.

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Current treatment of trypanosomosis in sub-Saharan Africa is associated with widespread inefficiency.There is therefore the need to find more effective drugs against the disease from promising traditional medicinal herbs. This work is aimed at evaluating ex vivo anti-trypanosomal effect of stem-bark extracts of S. longipedunculata against T. brucei brucei. One hundred microlitre of crude methanol, ethyl acetate and aqueous methanol extracts of S. longipedunculata at concentrations of 3 and 6 mg/ml each were mixed with 50 µl of blood containing 8.1 × 10 6 trypanosomes and incubated at 37°C for 90 min. Similarly, diminazene aceturate (10 µg/ml), physiological saline solution (50 µl) and blood (100 µl) containing trypanosomes only served as treated, negative and untreated controls, respectively. Motility of the parasite was monitored under light microscope (×400) at 5 min interval throughout the 90 min observation period. All experiments were done in duplicate. The mixtures were subsequently inoculated into rats that were not previously infected with trypanosomes. Phytochemical screening of the extracts revealed the presence of carbohydrates, cardiac glycosides, saponins, steroid, triterpenes, flavonoids and tannins. However, aqueous and ethyl acetate fractions were devoid of flavonoids. The crude methanol immobilized the parasites within 75 min, while ethyl acetate and aqueous extracts induced slight reduction in motility of the parasite at 90 min of incubation. However, inoculated rats developed infection and succumbed to the infection. It is concluded that the stem-bark of the plant possesses trypanostatic, but not trypanocidal, activity against the parasite.

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Diminazene Aceturate (Berenil) Modulates the Host Cellular and Inflammatory Responses to Trypanosoma congolense Infection

Cited by 68 publications

References 28 publications

The animal trypanosomiases and their chemotherapy: a review

The animal trypanosomiases and their chemotherapy: a review

Kupffer Cell p38 Mitogen-Activated Protein Kinase Signaling Drives Postburn Hepatic Damage and Pulmonary Inflammation When Alcohol Intoxication Precedes Burn Injury

Ex vivo trypanostatic effect of stem-bark extracts of Securidaca longipedunculata (Fres. Holl) against Trypanosoma brucei brucei

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