Histopathological and biochemical evaluation of the effects of elamipretide and methylprednisolone treatments on optic nerve, retina and brain damage in an experimental methanol poisoning model

Objective: This study aims to biochemically and histopathologically evaluate the protective and therapeutic effects of Elamipretide and Methylprednisolone on brain, optic nerve, and retinal toxicity caused by methanol poisoning. Method: In this study, 36 male Wistar Albino rats were divided into 6 groups, each consisting of 6 rats. The groups were as follows: Control, Methotrexate (MTX), MTX + Methanol, MTX + Methanol + Methylprednisolone (MPZ), MTX + Methanol + Elamipretide (SS31), and MTX + Methanol + Methylprednisolone + Elamipretide (MPZ+SS31). To establish an experimental model of methanol poisoning, all rats except the Control group were administered MTX at a dose of 0.3 mg/kg/day for 7 days. On the 8th day of the experiment, after administering methanol at a dose of 3 g/kg to all groups except the Control and MTX groups, the MPZ group received 1 mg/kg/day MPZ, the SS31 group received 5 mg/kg/day Elamipretide, and the MPZ+SS31 group received 1 mg/kg/day MPZ and 5 mg/kg/day Elamipretide for 3 days, with the first dose given 4 hours after methanol administration. The rats were sacrificed 8 hours after the last dose of the drugs. Histopathological and biochemical evaluations were conducted on the serum, caudatoputamen, and eye tissues of the rats. Results: A statistically significant difference was found between the groups in the cells of the caudate-putamen tissue (p=0.001). The highest ratio of Grade 1, 2, and 3 cells was observed in the Methanol group. There was no significant difference in the apoptotic index between the combined treatment group and the control group in the same tissue. The retinal degeneration score was found to be higher in the combined treatment group compared to the Methanol group (p=0.001) Conclusion: Elamipretide and methylprednisolone treatments, when applied in combination, have been observed to improve neuronal degeneration in the caudate-putamen tissue, optic nerve, and retinal degeneration, reduce oxidative stress and lipid peroxidation in these tissues, and particularly decrease apoptosis in brain tissue.