The effect of idebenone and corticosteroid treatment on methanol-induced toxic optic nerve and retinal damage in rats: biochemical and histopathological examination

Purpose: To evaluate the therapeutic effects of methylprednisolone, the CoenzymeQ10 (CoQ10) structural analogue idebenone, and both together on the optic nerve (ON) and retinal layers following methanol intoxication in rats with histopathological and biochemical methods.

Materials and methods: This experimental study was conducted with 30 male Wistar rats. The rats were divided into five equal groups depending on the treatment protocol:healthy controls (HC), methanol (M), methanol + methylprednisolone (MM), methanol + idebenone (MI), and methanol + methylprednisolone + idebenone (MMI).Distilled water was provided orally to the HC group, while 20% methanol was administered orally at a dose of 3 g/kg with a nasogastric tube to all rats in groups except the HC group. Four hours later, group MM received 1 mg/kg of intraperitoneal methylprednisolone for 10 days using an insulin syringe, and group MI received 20 mg/kg idebenone by nasogastric catheter for 28 days. MMI group was administered oral idebenone and intraperitoneal methylprednisolone at the same dose. Serum samples were obtained on the 28^th day for biochemical analysis and afterwards the rats were euthanized for histopathological examination and eyes were enucleated. ON was evaluated for circumference thickness, vascularization and number of astrocytes, also retinal layers were examined for structural changes by histopathological examination.

Results: Comparison of the antioxidant and oxidative stress biomarkers between the groups revealed no statistically significant difference (p > 0.05). By histopathological evaluation the most marked results were obtained by MMI group with an improvement of all parameters mentioned. There was no statistically significant difference between MM group and M group for RD score (p = 0.123). In addition, ON vacuolization in MI group (p < 0.001) and ON astrocyte increase in both MI and MMI groups were statistically significantly lower than in M group (p = 0.001, p = 0.001, respectively).

Conclusions: The early use (within hours) of idebenone and short-term methylprednisolone treatment together may protect against the retinal and ON damage developing after methanol ingestion in rats as guided by the histopathological data.