title: The effects of caffeic acid phenethyl ester in acute methanol toxicity on rat retina and optic nerve.
abstract: OBJECTIVE
  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 (0.3 mg/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, 0.5 g/kg ethanol was injected i.p. in ethanol group; 10 μmol/kg CAPE i.p. in CAPE group; serum physiologic i.p. in other groups. After 8 h, 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.
  
  
  CONCLUSIONS
  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.
authors: Department of Ophthalmology, Dicle University School of Medicine, Diyarbakır, Turkey. dralparslansahin@gmail.com
authors: Alparslan
authors: A
authors: Sahin
authors: Savaş
authors: S
authors: Kaya
authors: Gül
authors: G
authors: Türkcü
authors: Abdullah Kürşat
authors: AK
authors: Cingü
authors: Harun
authors: H
authors: Yüksel
authors: Fatih Mehmet
authors: FM
authors: Türkcü
authors: Hatice
authors: H
authors: Yüksel
authors: Yasin
authors: Y
authors: Cınar
authors: Seyhmus
authors: S
authors: Arı
authors: Muhammed
authors: M
authors: Sahin
authors: Ihsan
authors: I
authors: Caça
authors: Osman
authors: O
authors: Gökalp
mesh_terms: D000426:Alcohol Dehydrogenase / Q000378:metabolism; D000818:Animals; D000931:Antidotes / Q000494:pharmacology / Q000627:therapeutic use*; D002109:Caffeic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D000431:Ethanol / Q000494:pharmacology; D000077604:Fomepizole; D006801:Humans; D008297:Male; D000432:Methanol / Q000494:pharmacology / Q000506:poisoning*; D062105:Molecular Docking Simulation; D009900:Optic Nerve / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
chemical_list: D000931:Antidotes; D002109:Caffeic Acids; D011720:Pyrazoles; C010201:4-iodopyrazole; D000431:Ethanol; D000077604:Fomepizole; D000426:Alcohol Dehydrogenase; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol; D000432:Methanol