Biochemical and histological alterations of doxorubicin‐induced neurotoxicity in rats: Protective role of luteolin

Doxorubicin (DOX) is a chemotherapeutic drug used in the treatment of various cancer types. DOX toxic side effects include neuronopathy and memory deficits. We investigated the effect of the antioxidant luteolin (LUT: 50 or 100 mg/kg; per os) on DOX (2 mg/kg; intraperitoneal)-induced oxidative stress (OS), inflammation, and apoptosis in the brain of Wistar rats for 14 days. We observed that LUT reduced DOX-mediated increase in OS biomarkers-catalase, superoxide dismutase, glutathione-S-transferase, and glutathione peroxidase. LUT increased glutathione and total sulphydryl levels and alleviated DOX-induced increases in the levels of reactive oxygen and nitrogen species, lipid peroxidation, myeloperoxidase, nitric oxide, tumor necrosis factor-α, and interleukin-1β (IL-1β). Additionally, LUT suppressed caspase-3 activity, increased anti-inflammatory cytokine-IL-10 level, and reduced pathological lesions in the examined organs of rats cotreated with LUT and DOX. Collectively, cotreatment with LUT lessened DOX-induced neurotoxicity. Supplementation of LUT as a chemopreventive agent might be useful in patients undergoing DOX chemotherapy.