Iron-deficiency anemia and cardio-renal toxicity of doxorubicin in hypertensive rats.

Abstract

e19569 Background: Hypertension and anemia are common in patients with neoplasm and may increase the toxicity of anti-cancer drugs. This study evaluated cardio-renaltoxicity of doxorubicin (DOX) in combination with iron deficiency anemia (IDA) in Spontaneously Hypertensive Stroke Prone (SHRSP) rats. Methods: SHRSP rats were randomized into six groups (A-F; n=8 each). IDA was induced in groups A-D by 12 weeks low iron diet; groups E and F had normal diet. After 6 weekly DOX or control treatments (0.9% saline), echocardiography was performed and blood analyzed for hemoglobin (Hb) and transferrin saturation (% TSAT). Tissue sections and homogenates from heart and kidney samples were analyzed for markers of oxidative-nitrosative stress and inflammation. Results: IDA plus DOX was associated with significantly lower cardiac performance (% FS) and kidney function (CrCl) and a higher degree of cardio-renal oxidative-nitrosative stress and inflammation (Table). Conclusions: The results show that IDA can aggravate dose dependent DOX-induced cardio-renal toxicity in hypertensive rats and confirm that IDA significantly induces oxidative-nitrosative stress and inflammation. [Table: see text]