Beneficial pharmacological effects of levosimendan on antioxidant status of acute inflammation induced in paw of rat: involvement in inflammatory mediators.

Levosimendan (LEVO) is a new calcium sensitizer with positive inotropic and vasodilating properties that represents a new pharmacological class of inotropic drugs that stimulate elevated cardiac output. The purpose of this study was to examine anti-inflammatory effect and antioxidant activity of LEVO in a carrageenan (CAR)-induced inflammatory paw oedema rat model. The CAR-induced rat groups received LEVO 1, 2 and 3mg/kg by intraperitonally and indomethacin (IND) 25mg/kg by oral gavage. LEVO inhibited CAR-induced paw oedema and suppressed the production of TNF-, IL-1 and IL-6 at doses of 2 and 3mg/kg. In contrast to CAR-injected paws, 2 and 3mg/kg doses of LEVO and IND increased superoxide dismutase (SOD) activity and also both doses of LEVO, and IND decreased the 8-isoprostaglandin F2 (8-ISO) level. A 2mg/kg dose of LEVO produced 39%, 46%, 61% and 64.7% anti-inflammatory effects (p<0.0001) for the 1st, 2nd, 3rd and 4th hours, respectively. Other results of our current study have shown that SOD and glutathione for CAR-injected groups were lower, and 8-ISO level was higher than those for the healthy rat group. LEVO may be provided as a pharmacological agent in the prevention or treatment of diseases in which acute or chronic inflammation occurs based on a pathogenic factor.