In contrast to LID alone, the combination of LID and DOX resulted in a dose-dependent increase of mortality in SHR-SP rats; 13%, 25%, and 50% for DOX doses of 3, 4, and 5 mg/kg, respectively.
The data presented herein show that FCM at a total dose of 15 mg iron/kg BW resolves IDA and attenuates IDA- and DOX-associated cardiorenal toxicity in SHR-SP rats.
The development of hypertension in SHR-SP rats  was not affected by LID, DOX treatment, or combined treatment with DOX and FCM.
Therefore, clinical data in iron-deficient chronic heart failure (CHF) patients showing that FCM improved functional status, quality of life, and exercise capacity [27, 34] are in line with the FCM-based improvement of IDA- and DOX-associated stress and cardiac impairment in SHR-SP rats.
In the present study, combined treatment of iron-replete (ND-fed) SHR-SP rats with DOX and i.v.
SHR-SP is a cerebral stroke model of the hypertensive rat.
In fact, when removing the brains from both SHR-SP groups, we observed their surfaces and found that two of eight in the control group but none of eight in the Choto-san group had blood spots.
Nevertheless, we believe that the present study provided convincing evidence that Choto-san exerts a protective effect against cerebral stroke in SHR-SP.
Regarding this point, SHR-SP serves as a useful model for human multiple cerebral infarction, and Choto-san is considered to offer protection against this event.