title: Diminazene aceturate (Berenil), a new use for an old compound?
abstract: Diminazene aceturate or Berenil has been the drug of choice for treatment of animal trypanosomiasis. Although the compound has been in the market since 1955, its mechanisms of action have remained poorly understood. While some earlier reports show that Berenil possesses trypanolytic and trypanostatic properties, some studies show it may also indirectly affect the host immune system. Our recent extensive studies show that treatment with Berenil reduces pro-inflammatory cytokine (IL-6, IL-12 and TNF) production in macrophages in vivo and in vitro following stimulation with Trypanosoma congolense, lipopolysaccharide (LPS), unmethylated bacterial CpG motifs and Poly I:C. This global effect was not due to downregulation of Toll-like receptor (TLR) expression on innate immune cells. Instead, Berenil significantly downregulated phosphorylation of mitogen activated protein kinases (MAPKs, including ERK, p38 and JNK), signal transducer and activator of transcription (STAT) proteins (including STAT1 and STAT3) and NFκB p65 subunit, key signaling molecules and transcription factors involved in the production of proinflammatory cytokines. The ability of Berenil to downregulate major intracellular signaling pathways that lead to proinflammatory cytokine production suggests that it could be used to treat conditions caused by excessive production of inflammatory cytokines.
authors.affiliation: Department of Immunology, Faculty of Medicine, University of Manitoba, Canada.
authors.forename: Shiby
authors.initials: S
authors.lastname: Kuriakose
authors.affiliation: Department of Immunology, Faculty of Medicine, University of Manitoba, Canada. Electronic address: Jude.Uzonna@med.umanitoba.ca.
authors.forename: Jude E
authors.initials: JE
authors.lastname: Uzonna
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004133:Diminazene / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D016207:Cytokines; D014157:Transcription Factors; C003915:diminazene aceturate; D004133:Diminazene
keywords: African trypanosomiasis; Anti-inflammatory agent; Diminazene aceturate (Berenil); Immunomodulation; Management of chronic inflammatory conditions