Doxorubicin is an effective anti-neoplastic agent; the reported toxicities of DOX limit its use. Luteolin is a polyphenolic phytochemical that exhibits beneficial biological effects via several mechanisms. We investigate luteolin protective effects on hepatorenal toxicity associated with doxorubicin treatment in rats. For 2 weeks, randomly assigned rat cohorts were treated as follows: control, luteolin (100 mg/kg; per os), doxorubicin alone (2mg/kg; by intraperitoneal injection), co-treated cohorts received luteolin (50 and 100 mg/kg) in addition to doxorubicin. Treatment with doxorubicin alone significantly (p < 0.05) increased biomarkers of hepatorenal toxicities in the serum. Doxorubicin also reduced relative organ weights, antioxidant capacity, and anti-inflammatory cytokine interleukine-10. Doxorubicin also increased reactive oxygen and nitrogen species, lipid peroxidation, pro-inflammatory-interleukin-1β and tumour necrosis factor-α-cytokine, and apoptotic caspases-3 and -9). Morphological damage accompanied these biochemical alterations in the rat's liver and kidney treated with doxorubicin alone. Luteolin co-treatment dose-dependently abated doxorubicin-mediated toxic responses, improved antioxidant capacity and interleukine-10 level. Luteolin reduced (p < 0.05) lipid peroxidation, caspases-3 and -9 activities and marginally improved rats' survivability. Similarly, luteolin co-treated rats exhibited improvement in hepatorenal pathological lesions observed in rats treated with doxorubicin alone. In summary, luteolin co-treatment blocked doxorubicin-mediated hepatorenal injuries linked with pro-oxidative, inflammatory, and apoptotic mechanisms. Therefore, luteolin can act as a chemoprotective agent in abating toxicities associated with doxorubicin usage and improve its therapeutic efficacy.
Keywords: Doxorubicin; antioxidant; apoptosis and rat; hepatorenal toxicity; inflammation; luteolin; oxidative stress.