Objective: This study was designed to investigate the therapeutic potential of selected bioflavonoids on cART-induced neurological disorders.

Background: Long term usage of combination antiretroviral therapy (cART) has been associated with neurological disorders from varying toxicities.

Method: Thirty-five male Wistar rats were randomly divided into seven groups viz: control (distilled water), N: 50 mg/kg Naringenin, Q: 50 mg/kg Quercetin, 24 mg/kg cART, CN: 24 mg/kg cART + 50 mg/kg Naringenin, CQ: 24 mg/kg cART + 50 mg/kg Quercetin and DMSO: 1% v/v Dimethyl Sulfoxide. The animals were subjected to open field neurobehavioral test after which they were euthanized on the 57th day, and tissues (cerebellum and prefrontal cortex) processed for Tumor necrosis factor alpha (TNF α), histochemical (Giemsa), and immunohistochemical (Monoamine oxidase B) tests. Ethical clearance protocol number: CMUL/HREC/03/17/113.

Results: There was an increase in the TNF α level in the group that received cART only (219.6 ± 5.9) when compared to the control (196.4 ± 7.3), and CN (197.5 ± 2.5). Oxidative stress markers showed that antioxidant enzymes SOD, GSH and CAT decreased significantly in cART compared to control, CN and CQ, whereas, MDA levels increased significantly. Behavioural and motor assessment test results showed that there was significant decrease in the locomotor activity, rearing, grooming, and an increased immobility time in cART group compared to the control. Animals that received both cART and bioflavonoids showed a significant increase in locomotor activity compared to cART. In addition, the morphology of the cerebellar tissues were well preserved in the control group but the granular and Purkinje cells were more distinct and finer in groups that received Naringenin, and Quercetin. However, there was a significant decrease (p<0.05) in the granular, and Purkinje cells of cART group compared to the groups that received a combination of cART and bioflavonoids (CN and CQ). Likewise, monoamine oxidase B expression in cART was significantly upregulated compared to control.

Conclusion: This study demonstrates that Naringenin and Quercetin are capable of serving as anti-inflammatory agents as well as prevent cART induced cerebellar movement disorders and prefrontal cortex perturbations.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/combination-antiretroviral-therapy-cart-induced-cerebellar-and-prefrontal-cortex-disorders-a-study-on-the-impact-of-naringenin-and-quercetin/