Oral administration of HE3286 resulted in an almost complete resolution of CVB-induced myocarditis in mice, demonstrating better efficacy than dexamethasone in reducing the inflammatory response.
Does HE3286 improve histological and immunohistochemical signs of myocarditis in BALB/c mice infected with coxsackie B3 virus compared to dexamethasone or vehicle?
HE3286 showed superior efficacy to dexamethasone in resolving inflammation and tissue remodeling in a murine model of viral myocarditis.
Cell-mediated immune events play a role in the pathogenesis of myocarditis provoked by Group B coxsackievirus (CVB). Studies indicated the synthetic derivative of androstene-3β,7β,17β-triol, HE3286 (17α-ethynyl-5-androstene-3β,7β,17β-triol), may ameliorate the course of immunoinflammatory and autoimmune diseases in rodents. The aim of this study was to evaluate effects of HE3286 on histological signs of CVB-induced myocarditis. BALB/c mice were infected with coxsackie B3 virus (CB3V) and treated by intraperitoneal administration of dexamethasone (Dex) or by oral gavage with HE3286 or with its vehicle, HERF405, for 18 days. Mice were sacrificed and hearts were explanted for histological and immunohistochemical analysis (TNF-α, IL-6, MMP9, ADAM10 and HSP-70). Heart tissues of Dex-treated mice showed a better histological structure compared with mice treated with HERF405. An almost complete resolution of myocarditis was observed in HE3286-treated mice as evidenced by lack of inflammatory infiltration. Immunohistochemical findings confirmed HE3286 had a more pronounced effect than Dex in reducing inflammatory response associated with in situ modulation of cytokine expression and tissue remodeling. Our data demonstrate HE3286 has better results in inhibiting establishment and progression of murine CVB-induced myocarditis than Dex, suggesting this drug may also have a therapeutic role in treatment of CVB-induced myocarditis.
Castrogiovanni et al. (Thu,) conducted a other in CVB-induced myocarditis. HE3286 vs. Dexamethasone or vehicle (HERF405) was evaluated on Histological signs of CVB-induced myocarditis and immunohistochemical analysis. Oral administration of HE3286 resulted in an almost complete resolution of CVB-induced myocarditis in mice, demonstrating better efficacy than dexamethasone in reducing the inflammatory response.
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