Protective Effect of Dietary Ghrelin-Containing Salmon Stomach Extract on Mortality and Cardiotoxicity in Doxorubicin-Induced Mouse Model of Heart Failure.

Ghrelin exhibits a cardioprotective effect. We examined whether orally administered ghrelin-containing salmon stomach extract (sSE) instead of chemically synthesized ghrelin protects against doxorubicin (DOX)-induced cardiotoxicity in mice. Mice were divided into four groups: (i) the control, (ii) DOX groups were fed a control diet (AIN-93G), (iii) the sSE, and (iv) DOX + sSE groups were fed a 10% sSE diet (AIN-93G + 10% sSE). After a 4-week pretreatment of sSE, DOX or saline was administered to the corresponding groups by intraperitoneal injection. The groups fed the 10% sSE diet consumed significantly more food than the groups fed the control diet before the DOX injection. No mortality was observed in the DOX + sSE group, whereas 40% (2 of 5) mortality was observed in the DOX group. Compared with the DOX group, levels of ascites and plasma cardiac troponin I improved in the DOX + sSE group. Significantly lesser DOX-induced collagen accumulation was observed in the left heart ventricle of the DOX group than in that of the DOX + sSE group. These results suggest that the dietary ghrelin contained in sSE mimics synthetic ghrelin in cardioprotective effect. Ghrelin in sSE (45 pmol/g) and the food intake-stimulating effect of sSE may explain, at least in part, the protective effect of orally administered teleost ghrelin.