Arbutin promotes functional recovery following lysolecithin-induced local model of demyelination model in rat optic chiasm

Background and Objective: Multiple sclerosis (MS) is an autoimmune and neurodegenerative disease in young adult. Visual disturbance is involved in more than 70% of MS patients as the earliest symptoms. Hydroquinone derivations such as Arbutin has potential role as a free radical scavenger and anti-inflammatory agent which has not been studied in experimental model of demyelination yet. In this study, the effects of Arbutin administration on myelin repair and functional recovery of optic chiasm were investigated. Materials and Methods: Eighty adult male wistar rats weighing 200–250 g were obtained and divided into following groups (n=8): Intact group, Saline groups, LPC groups and treatment groups. Under stereotaxic procedure, local demyelination was induced by administration of LPC (1%, 2μL) into the rat optic chiasm. Rats treated by daily injection of Arbutin (50mg/kg, i.p) until the end of each animal group experiment (3, 7, 14 days after LPC injection) as well an equivalent volume of saline for LPC group animals. Visual-evoked potentials (VEPs) recording was performed for evaluating the function of optic pathway at 3, 7 and 14 days post lesions. P1-N1 latency and amplitude was measured by e-probe software. Myelin specific staining (Luxol Fast Blue) was also carried out for assessment of myelin repair. To evaluate the anti-inflammatory effect of Arbutin, real time-PCR was used by which inflammatory (IL1, Il17, TNF-α) and non-inflammatory (IL10) cytokines gene expression were investigated. The data was analyzed by two-way ANOVA followed by Bonferroni post-test using Graph pad PRISM software. Results: Electrophysiological data indicated that Arbutin significantly reduced P1-N1 latency at 7 and 14 days following optic chiasm demyelination compared to the same time points of LPC treated animals (p<0.05). Histological study in agreement with electrophysiological data proved that demyelination extension in optic chiasm was considerably reduced in arbutin treated groups at 7 and 14 days post demyelination injection (dpi) in comparison with LPC treated animals (p<0.001). q-PCR analyses of optic chiasm samples revealed that Arbutin treatment remarkably reduced the level of IL-1β expression especially at 7 dpi (p<0.001) and the expression level of IL17 and TNF-α at 3 and 7 dpi respectively compared to LPC groups (p<0.05, p<0.001). Arbutin had notably decreased the expression of anti-inflammatory gene (IL-10) at all-time points compared to LPC groups respectively (p<0.0001, 0.01). These data indicate that Arbutin treatment at 50 mg/kg dose have an inhibitory effect on inflammatory cascade of events involved in pathogenesis of MS disease. Conclusions: Our results showed that Arbutin facilitate myelin repair and restore VEP response in the demyelinated optic chiasm. Thus, Arbutin could have therapeutic potential for demyelinating disorders such as Multiple Sclerosis.

کلیدواژه ها:

Lysolecethin ، Arbutin ، Demyelination ، Optic chiasm ، VEP