ラットにおけるドキソルビシン誘発心毒性に対するモンテルカストの保護効果

We investigated possible protective effect of montelukast (MTL) on doxorubicin (DOX)-induced cardiac damage in a rat model.

Thirty-five rats were randomised into 5 equal groups including 7 rats in each group: Control (C) group; MTL group (10 mg/kg MTL via the orogastric route for 10 days); DOX group (single dose of 20 mg/kg) DOX intraperitoneally (i.p); DOX+MTL group (3 days after the single dose of 20 mg/kg DOX i.p., 10 mg/kg MTL continued for 10 days via the orogastric route); and MTL+DOX group (10 mg/kg MTL continued for 10 days via the orogastric route, single dose 20 mg/kg DOX administrated after last dose MTL).

In the MTL + DOX group, a significant decrease in mean arterial blood pressure (MBP) and a marked reduction in oxygen saturation were observed together. On ECG, QT interval indicated a significant increase in DOX group compared to MTL group and a significant increase in MTL+DOX group, compared to C and MTL groups. DOX treatment led to significant increase in MDA levels, decrease in SOD levels, and increase in MPO activities in the heart and aorta tissue. Myocyte degeneration seen in DOX group significantly reduced in the MTL+DOX and DOX+MTL groups histopathologicaly.

Our results indicate that MTL has protective effects against DOX-induced cardiotoxicity in rats.