Doxorubicin-mediated nephrotoxicity is associated with tubuloglomerular dysfunction accompanied with oxido-inflammatory stress: Implication of lutein, a natural carotenoid

Abstract

Renal toxicity is one of the pathological consequences of doxorubicin therapy in cancer patients. Meanwhile the renoprotective impact of lutein, a natural carotenoid widely known for its health benefits has not been fully studied. Hence, this study was designed to investigate the renal protective potential of lutein on doxorubicin induced renal toxicity. Animals were pretreated with lutein (40 mg/kg i.p) 25 days prior to doxorubicin (15 mg/kg i.p) exposure for 3 consecutive days. Following 28 days experimentation, animals were euthanized and kidney and blood samples were collected, processed for biochemical assay as well as histological evaluation. Our results showed that exposure to doxorubicin significantly increased serum creatinine, urea and elicited electrolyte imbalance accompanied with oxidative stress, inflammation, apoptosis and dysregulated autophagic process as well as distorted histoarchitecture. Interestingly, pretreatment with lutein offered renal protection by reversing these aberrant pathological changes caused by doxorubicin. Conclusively, lutein protects against doxorubicin-mediated nephrotoxicity via inhibition of oxidative stress, inflammation, apoptosis as well as suppression of tubuloglomerular dysfunction.