Poster Presenter

1-Methylnicotinamide And 1,4-Dimethyl Pyridine Exerts Liver Protective Activity By The Prostacyclin Dependent Mechanism
A Jakubowski, M Sternak; R Biedron, K Jablonski, L Mateuszuk, M Gajda; W Szczepanski; J Marcinkiewicz and S Chlopicki
Poland

Nicotinamide metabolite 1-methylnicotinamide (MNA) and its derivative 1,4-dimethylpyridine (1,4-DMP) exerts anti-thrombotic and anti-inflammatory activity mediated by a prostacyclin pathway.

Hepatoprotective actions of MNA (30-500mg/kg) and 1,4-DMP (10-100mg/kg) were studied in the presence or absence of prostacycline receptor antagonist-RO3244794 (10mg/kg) in concanavalin A-induced (ConA; 20mg/kg) inflammatory liver injury. Liver damage was assessed by measurement of plasma transaminases (AlaAT, AspAT) and cytokines (IL-4, INTγ, TNFα), estimation of 24h survival rate, histopathological and immunohistological (OCT) staining. The effect of prostacycline on IL-4, INTγ and TNFα production by isolated spleen lymphocytes was also analyzed.

MNA and 1,4-DMP diminished ConA-induced rise in transaminases, abolished histopathological injury and infiltration with lymphocytesT. This activity improved 24h survival similary to dexamethasone (0.5mg/kg). MNA and 1,4-DMP diminished rise in plasma cytokines 2h after ConA administration, with exception of INTγ which was not affected. Prostacyclin decreased production of IL-4 and TNFα but not INTγ by isolated spleen lymphocytes. The protective effects of MNA and 1,4-DMP were abolished by pretreatment with RO3244794.

MNA and 1,4-DMP displayed hepatoprotective effects which depends on its anti-inflammatory activity mediated by a prostacyclin pathway. Findings suggest that MNA and 1,4-DMP regulate inflammatory response to ConA by modulation of lymphocytesT/macrophages interactions resulting in prevention of pro-inflammatory cytokines overproduction.