Development of drugs for anticancer drug-induced cardiotoxicity using acyl ghrelin and des-acyl ghrelin extracted from the stomach of salmon and tuna

Doxorubicin (DOX) is known to cause irreversible dysfunction of the heart. Recent reports indicate that acyl ghrelin (AG) and des-acyl ghrelin (DAG) prevent the DOX-induced cardiotoxicity. In addition, AG-containing salmon stomach extracts improve cardiac dysfunction as well. In this study, we evaluated the effects of AG and DAG extracted from the stomach of salmon and tuna on the human ghrelin receptors (hGHSR-1a) and examined their therapeutic effects against the DOX-induced cardiotoxicity in vitro. The activity of AG and DAG was evaluated using CellKey, which can measure cell membrane impedance as the activity of hGHSR-1a in HEK293A cells expressing hGHSR-1a. Both salmon and tuna AG activated hGHSR-1a, although these activities were 1000 times lower than those induced by human and rat AG. However, maximum activation of salmon and tuna AG was similar to those of human and rat AG. In addition, DAG failed to activate hGHSR-1a. These findings indicate that extracted AG from salmon and tuna stomach can be resources for drugs as a hGHSR-1a receptor activator. Further study is now underway to demonstrate therapeutic effects of salmon and tuna AG and DAG on the DOX-induced cardiotoxicity using cardiac H9C2 cells.