Diminazene aceturate

Diminazene aceturate (Diminazene diaceturate) is an anti-trypanosome agent for livestock. The main biochemical mechanism of the trypanocidal actions of Diminazene aceturate is by binding to trypanosomal kinetoplast DNA (kDNA) in a non-intercalative manner through specific interaction with sites rich in adenine-thymine base pairs. Diminazene aceturate is also an angiotensin-converting enzyme 2 (ACE2) activator and has strong and potent anti-inflammatory properties[1][2][3].

Pre-treatment of bone marrow-derived macrophages (BMDM) and dendritic cells (BMDC) with Diminazene aceturate (Berenil) downregulats LPS-, CpG- and Poly I:C-induced proinflammatory cytokine production, suggesting that it may be affecting common pathways through which these molecules stimulate proinflammatory cytokine production. Indeed, Diminazene aceturate does not alter the expression of different TLRs (including TLR2, TLR4 and TLR9), on macrophages and DCs when assessed by flow cytometry. Instead, Diminazene aceturate dramatically downregulats the phosphorylation of MAPKs (ERK, p38 and JNK), STATs (STAT1 and STAT3) and NFκB p65 subunit, which are key signaling molecules and transcription factors involved in the production of proinflammatory cytokines[2].

Diminazene aceturate (14 mg/kg; intraperitoneal injection; female BALB/c mice and C57BL/6 mice) treatment significantly reduces the percentages of CD25+ cells, a concomitant reduction in the percentage of regulatory (CD4+Foxp3+) T cells and a striking reduction in serum levels of disease exacerbating pro-inflammatory cytokines including IL-6, IL-12, TNF and IFN-γ[1]. Animal Model: Female BALB/c mice and C57BL/6 mice (6-8 week old) infected with T. congolense variant antigenic type TC1[1]

[1]. Kuriakose S, et al. Diminazene aceturate (Berenil) modulates the host cellular and inflammatory responses to Trypanosoma congolense infection. PLoS One. 2012;7(11):e48696. [2]. Kuriakose S, et al. Diminazene aceturate (Berenil), a new use for an old compound• Int Immunopharmacol. 2014 Aug;21(2):342-5. [3]. Castardeli C, et al. The ACE 2 activator diminazene aceturate (DIZE) improves left ventricular diastolic dysfunction following myocardial infarction in rats. Biomed Pharmacother. 2018 Nov;107:212-218.