Effect of carnosine on histamine release and mortality during compound 48/80-induced shock in rats

ABSTRACT

Carnosine is an endogenous dipeptide found at high concentrations in many tissues, Early studies have demonstrated a link between carnosine, free histidine and histamine synthesis following several types of physiologic stresses. However, the precise role of carnosine and histamine in the physiologic response to stress is unknown. The present work was conducted to study the effect of carnosine administration on the lethal shock induced in rats by compound 48/80, a histamine releasing agent and whether this effect was mediated by an action on mast cell histamine release, in-vitro. The in-vivo study included 6 groups of mature albino rats which received I.P. injection of either; saline, carnosine [200 mg/kg], compound 48/80 [5 mg/kg], or carnosine [50, 100 or 200 mg/kg] followed 30 mm later by compound 48/80 [5 mg/kg]. All rats were observed for 2 hours recording mortality and survival time in each group. The in-vitro study examined the effect on isolated rat mesenteric mast cells, of the following; saline, carnosine [2-16 mg/ml], compound 48/80 [1-8 ug/ml] and carnosine [2-16 mg/ml]+compound 48/80 [4 ug/ml]. Results showed that treatment with compound 48/50 [5 mg/kg] leads to 100% mortality in mature rats, while no deaths were observed in the saline and carnosine treated groups. Pretreatment with carnosine produced significant attenuation of the lethal effect of compound 48/80, with up to 67% protection in treated animals. Examination of mast cells revealed dose-dependent degranulation by compound 48/80 and insignificant changes by carnosine treatment. Addition of carnosine to compound 48/80 leads to significant inhibition of compound 48/80-induced mast cell degranulation and histamine release. It is concluded that carnosine could attenuate the lethal effect of compound 48/80-induced shock in rats and this protective effect was mediated, at least in pan, by decreasing histamine release from mast cells