Luteolin attenuates doxorubicin-induced derangements of liver and kidney by reducing oxidative and inflammatory stress to suppress apoptosis

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-1 beta and tumour necrosis factor-alpha-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.

Automated summary

Luteolin helps protect against hepatorenal toxicity caused by doxorubicin by improving antioxidant capacity and inhibiting oxidative, inflammatory, and apoptotic pathways. Its co-treatment with doxorubicin can reduce toxic responses, enhance survivability, and improve therapeutic efficacy.