THAA0103 | EXPLORING VITAMIN E’S (TOCOPHEROL) NEUROPROTECTIVE MECHANISM IN MITIGATING SYMPTOMS OF ISONIAZID-INDUCED PERIPHERAL NEUROPATHY IN RATS, FOCUSING ON HIV-TUBERCULOSIS COMORBIDITY

Akpevwe Emmanuella Benson | University of Benin, Benin City, Nigeria

Isoniazid (INH), a primary agent in tuberculosis (TB) therapy, is associated with neurotoxicity, including peripheral neuropathy. This is particularly concerning in individuals co-infected with HIV, who often require concurrent TB treatment, thereby increasing their susceptibility to drug-induced neuropathies. Pyridoxine (vitamin B6) is coadministered with INH to mitigate this effect; however, high doses can cause B6-induced neuropathy. This study investigated the neuroprotective potential of vitamin E (tocopherol) as an adjunct therapy for INH-induced neuropathy, specifically its effects on the calcium-activated potassium channels subfamily N1 (KCNN1), a key regulator of neuronal excitability. The primary objectives were to evaluate vitamin E’s effect on KCNN1 gene expression in a rat model of INH-induced peripheral neuropathy and assess its potential as an adjunct therapy in HIV-TB co-infected individuals undergoing INH treatment. The Faculty of Pharmacy Ethics Committee at the University of Benin gave its approval for the study. Adult male Wistar rats (150–200 g) were acclimatized for 14 days and randomized into six groups (n=5). Groups were treated orally for 14 days with: INH (93 mg/kg); Vitamin E (23.6, 46.5, or 93 mg/kg) + INH; pyridoxine (8.86 mg/kg) + INH; and deionized water (0.5 mL/day). On day 7, doses were adjusted for weight. On day 14, animals were sacrificed, and brain samples were collected for KCNN1 gene expression analysis via PCR. Statistical analysis was conducted using GraphPad Prism 8.0.1 with significance at P<0.05. The INH-only group showed significant downregulation of KCNN1 expression compared to control. Vitamin E, especially at 93 mg/kg, restored KCNN1 expression to levels comparable to the pyridoxine group. The observed upregulation, in conjunction with vitamin E’s antioxidant and membrane-stabilizing attributes, indicates a potential neuroprotective mechanism. In HIV-TB co-infected patients on INH, vitamin E may serve as a valuable adjunct to pyridoxine, potentially mitigating neuropathy while also boosting immune function. Vitamin E shows potential as an adjunct therapy in INH-induced neuropathy via modulation of KCNN1 gene expression. This is relevant for HIV-TB co-infected patients at elevated neuropathy risk. Further studies are needed to compare vitamin E and pyridoxine, optimize dosing, and assess long-term efficacy.