Nigella sativa oil alleviates doxorubicin-induced cardiomyopathy and neurobehavioral changes in mice: In vivo and in-silico study

Objective: To investigate the effect of Nigella sativa oil on cardiomyopathy and neurobehavioral changes induced by doxorubicin in mice. Methods: Swiss strain of albino female mice were divided into 6 groups of 5 animals in each: Group I (control group), group II (doxorubicin, 10 mg/kg, i.v.), group III, IV, and V (Nigella sativa oil; 1.5, 3, and 6 mL/kg, respectively), group ? (Nigella sativa oil per se; 6 mL/kg, p.o.). The duration of treatment was 15 d (10 days' pre-treatment and 5 days' post-treatment) and doxorubicin was administered on day 11th of the treatment schedule. Following Nigella sativa oil treatment, neurobehavioral tests, cardiac hypertrophy tests, and biochemical tests in serum and tissues were performed. Neurological tests included assessment of anxiety-like behavior in the elevated plus maze, spontaneous alternation behavior in the cross maze, and depression-like behavior in modified forced swim tests. Biochemical tests included serum lactate dehydrogenase and creatinine kinase-MB, malondialdehyde and reduced glutathione in tissues. Lastly, molecular docking was used to estimate the affinity of the phytoconstituents of Nigella sativa oil with histone deacetylases. Results: Nigella sativa oil treatment significantly (P < 0.001) restored doxorubicin-induced neurobehavioral changes, decreased lactate dehydrogenase and creatinine kinase-MB in the plasma, malondialdehyde contents in tissues, and increased reduced glutathione level. Besides, no significant alteration was observed in Nigella sativa oil per se group as compared to the control. Molecular docking showed that Nigella sativa oil components had appreciable binding affinitiy with the protein cavities of HDAC1 and HDAC6. Conclusions: The result shows that Nigella sativa oil exerts anxiolytic, antidepressant, and memory-enhancing effects in addition to cardioprotective effect against doxorubicin-induced cardiomyopathy in mice. The modulatory effect of Nigella sativa oil on oxidative stress could contribute to the cardioprotective effect and associated neurobehavioral changes in mice.