The effects of caffeic acid phenethyl ester in acute methanol toxicity on rat retina and optic nerve

摘要

Purpose: We aimed to test caffeic acid phenethyl ester (CAPE) as an antidote for acute methanol (MeOH) toxicity and to compare it with ethanol. Methods: This study included five groups, each containing eight rats. The groups were control, methotrexate (MTX), MeOH, ethanol and CAPE. All rats except control group were treated with intraperitoneal (i.p.) MTX (0.3mg/kg/d) for 7 d. At the 8th day of the experiment, i.p. injection of MeOH (3 g/kg) was administered in MeOH, ethanol and CAPE groups. Four hours after MeOH treatment, 0.5g/kg ethanol was injected i.p. in ethanol group; 10μmol/kg CAPE i.p. in CAPE group; serum physiologic i.p. in other groups. After 8h, rats were anaesthetized and sacrificed. Total anti-oxidant status (TAS), total oxidant status (TOS) were measured on the dissected and excised retina and optic nerve samples. Fellow eyes were used for histopathologic evaluation and the cell count of retinal ganglion cell (RGC) layer. In addition, interactions of alcohol dehydrogenase with CAPE, ethanol, MeOH and pyrazole derivatives were investigated. Results: Either CAPE or ethanol co-treatment decreased the TOS levels and increased the TAS levels compared to the MeOH group. MeOH treatment decreased the mean cell count in RGC layer. CAPE co-treatment significantly prevented cell loss (p=0.040). Besides, in silico calculations showed that binding affinity of CAPE to alcohol dehydrogenase was higher than those of MeOH, ethanol, and pyrazole derivatives were. Conclusion: This study demonstrated that CAPE treatment decreased the oxidative stress in acute MeOH intoxication in the retina and optic nerve; beside that, protected RGC layer histology. In silico, CAPE had higher affinity score than MeOH, ethanol, pyrazole and pyrazole derivatives in the case of interaction with alcohol dehydrogenase.