Cardiovascular Protection with Sulfasalazine During Doxorubicin Challenge: Evidence from Oxidative and Histologic...

Anthracycline cardiotoxicity involves early oxidative-inflammatory injury to the myocardium and vasculature. Repurposing anti-inflammatory agents may offer pragmatic cardioprotection. The purpose of this study is to evaluate whether sulfasalazine (SSZ) mitigates doxorubicin (DOX)-induced myocardial and aortic injury in rats. Twenty-eight male Wistar albino rats were randomized to: Control (vehicle, n = 8), DOX (20 mg/kg i.p., single dose; n = 10), and SSZ + DOX (SSZ 300 mg/kg i.p. once daily for 3 days, then DOX 20 mg/kg i.p.; n = 10). At 24 h post-DOX, ECG and invasive blood pressure (BP) were recorded. The heart and thoracic aorta were harvested for histopathology and oxidative stress assays (MDA, SOD, GSH, CAT; composite indices where applicable). Compared with SSZ + DOX, the DOX group exhibited higher BP and greater arrhythmic burden. In the aorta, DOX elevated MDA and reduced SOD, GSH, and CAT versus the control, whereas SSZ + DOX shifted these toward control values. In the myocardium, DOX decreased SOD and increased oxidative index; SSZ + DOX attenuated histological injury (edema, hemorrhage, cardiomyocyte degeneration) and restored aortic intima-media thickness toward control. Heart rate was lower in SSZ + DOX than other groups. Short-course SSZ pretreatment alleviated early DOX-induced oxidative stress and structural damage in myocardial and aortic tissues, with concurrent improvement in hemodynamic and ECG profiles. These data support further dose-timing optimization and longer-term functional studies to define SSZ's translational potential as an adjunct cardioprotective strategy during anthracycline exposure.