Levetiracetam mitigates doxorubicin-induced Oxidative stress associated with Cognitive impairments and Neurodegeneration in experimental rats: In vivo and Molecular Modelling Studies

Abstract

Cognitive dysfunction frequently arises as a complication of doxorubicin (DOX) in cancer chemotherapy. This investigation assesses the neuroprotective potential of levetiracetam (LEVE) in countering DOX resulted cognitive impairments, oxidative stress, and neuronal apoptosis in rats. The experimental rats of the Sprague-Dawley strain (males) were divided into control, challenge, and treatment groups. DOX (2 mg/kg, i.p.) was used as a challenge and dosed four times (one dose per week) to animals, while LEVE (100 and 200 mg/kg) was administered for 30 days orally to the treatment groups. The cognitive defects were studied by means of a novel object recognition (NOR) test. The oxidative stress biomarkers (MDA, CAT, and GSH), and apoptosis-related neurodegenerative targets (Bcl2, Bax, and Caspase-3) were studied in the homogenate of brain. The information from the study showed that DOX administration significantly lessened the explorative time and discriminative index. Besides, DOX was found to enhance the markers indicative of oxidative stress and neurodegeneration in brain homogenate. LEVE exhibited a dose-dependent reversal of DOX-induced changes in cognitive parameters as well as oxidative (reduced MDA; elevated GSH levels) and neurodegenerative (elevated Bcl2; reduced Bax and Caspase-3 levels) biomarkers. At the end, molecular modelling approaches were added to strengthen our results. In conclusion, observations of the study indicated that LEVE enhanced the cognitive defect mitigated by DOX. The neuroprotective property of LEVE can be related to the attenuation of neurodegenerative biomarker values, which in turn is due to a reduction in oxidative stress.