The effect of halofuginone on radiation-induced cardiovascular injury

Purpose: The main purpose of this study was to evaluate the effects of Halofuginone on radiation-induced cardiovascular injury in a rat model. Methods: Sixty Wistar-Albino rats were divided into six groups (the control group, radiotherapy (RT) only group Irradiation (IR), 2.5 and 5 μg Halofuginone groups (Hal (2.5)/C and Hal (5.0)/C), and RT plus 2.5 and 5 μg Halofuginone groups (Hal (2.5)/IR and Hal (5.0)/IR). Rats were exposed to a single dose of 12 Gy irradiation generated by a linear accelerator. Halofuginone was applied intraperitoneally with daily doses. At the 6th and 16th weeks of RT, 5 rats from each group sacrificed and; heart and thoracic aorta tissues removed for both light microscopic and electron microscopic examinations. Results: Light microscopic examinations revealed that the endocardial thickness of all study groups was significantly different at 6th and 16th week of RT (p < 0.001 for both). Pair-wise comparisons showed that the differences were significant in IRHal (2.5)/IR (p < 0.001); IR-Hal (5.0)/IR (p < 0.001); and Hal (2.5)/IR-Hal (5.0)/IR (p = 0.001) at 16th week of RT. There were significant differences within the study groups regarding to the thoracic aorta fibrosis scores only at 16 th week of RT (p = 0.002). Electron microscopic examinations demonstrated that there were significant differences between all the groups with respect to heart mitochondria scores at both 6th week and 16th weeks of RT (p < 0.001 for both). The differences between Hal (2.5)/IR and Hal (5.0)/IR with respect to the heart mitochondria scores were significant only at 16th week of RT (p = 0.001). Conclusion: These data demonstrated that Halofuginone may improve radiation-induced cardiovascular injury. The most prominent improvement was observed in higher dose of Halofuginone group after long term follow-up.