Preventive mechanisms of lutein on doxorubicin-induced vasculopathy in male Wistar rat

Doxorubicin (DOX) treatment has been well-reported to hamper heart and arterial function, limiting its clinical application. Meanwhile lutein (LUT) has shown promising therapeutic prospects against many diseases, but no report has shown whether LUT can prevent DOX-associated vascular toxicity. This study deciphers the mechanism of Lutein's preventive effect against DOX-induced vascular toxicity using rat model. Twenty-four rats were grouped into the control (10 mL/kg distilled water with 1% dimethyl sulfoxide (DMSO), the DOX (15 mg/kg DOX in 1% DMSO), Lutein (LUT: 40 mg/kg) and LUT+DOX groups and used for this study. Male experimental rats were pretreated with Lutein and distilled water in 1% DMSO for 28 days to establish a preventive experimental model while, DOX were given to DOX and LUT+DOX groups for 3 days starting from day 25. Vascular function, oxido-inflammatory, aortic apoptotic, autophagy and histopathology were assessed. lutein pretreatment mechanistically showed upregulation of nitric oxide (NO) bioavailability, reducing endothelin-1 (ET-1), increased glutathione (GSH), superoxide dismutase (SOD), glutathione S-transferase (GST) as well as catalase while reducing inflammation (tumor necrosis factor-α and interleukin-6) and apoptosis (caspase 3) were significantly reduced through modulation of autophagic processes (Beclin-1/mammalian target of rapamycin (mTOR)). Also, histopathological changes were markedly alleviated. This study suggests that lutein-mediated vaso-preventive effect against DOX-induced vascular toxicity by preserving the vascular functions.