The protective effects of caffeic acid phenethyl ester in isoniazid and ethambutol-induced ocular toxicity of rats

Cutan Ocul Toxicol. 2013 Sep;32(3):228-33. doi: 10.3109/15569527.2012.759958. Epub 2013 Jan 25.


Purpose: This study intended to examine the effect of caffeic acid phenethyl ester (CAPE) on isoniazid (INH) and/or ethambutol (ETM)-induced retina and optic nerve toxicity in a rat model.

Methods: This study included eight groups, each containing 10 rats. The groups were Control, INH, ETM, CAPE, INH+CAPE, ETM+CAPE, INH+ETM and INH+ETM+CAPE. Rats were given orally 50 mg/kg/d of INH and 50 mg/kg/d of ETM in tap water for 30 d. 10 μmol/kg of CAPE were intraperitoneally injected for 30 d. The first dose of CAPE was given 24 h before the INH and ETM treatment and continued until sacrifice. Control group was given only tap water for 30 d. Rats were anaesthetized and sacrificed on the 30th day of experiment. Superoxide dismutase (SOD) activities, malondialdehyde (MDA), 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 retinal ganglion cell (RGC) count. In addition, CAPE, INH and ETM interaction with SOD isoforms were calculated in silico.

Results: The SOD activity and TAS levels were found significantly higher in CAPE-treated groups compared to INH and/or ETM-treated groups (p < 0.0001). But the MDA, and TOS levels were significantly lower in CAPE-treated groups (p < 0.0001). The mean RGC count is significantly decreased in INH, ETM and INH+ETM groups compared with INH+CAPE, ETM+CAPE and INH+ETM+CAPE groups, respectively (p values 0.001, 0.042, and 0.001 respectively). Besides, in silico calculations showed that binding affinity of CAPE to SOD isotypes was higher than that of INH and ETM.

Conclusion: This study demonstrates that CAPE treatment may decrease the oxidative stress in the retina and optic nerve of INH- and ETM-treated rats and may prevent RGC loss. As an underlying mechanism, CAPE and SOD interaction seems crucial for alleviation of ocular oxidative stress and RGCs toxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caffeic Acids / administration & dosage*
  • Ethambutol / administration & dosage
  • Ethambutol / adverse effects
  • Isoniazid / administration & dosage
  • Isoniazid / adverse effects
  • Male
  • Malondialdehyde / metabolism
  • Optic Nerve Diseases / chemically induced
  • Optic Nerve Diseases / metabolism
  • Oxidative Stress / drug effects
  • Phenylethyl Alcohol / administration & dosage
  • Phenylethyl Alcohol / analogs & derivatives*
  • Protective Agents / administration & dosage*
  • Rats
  • Rats, Sprague-Dawley
  • Retinal Diseases / chemically induced
  • Retinal Diseases / metabolism
  • Retinal Diseases / pathology
  • Retinal Ganglion Cells / pathology
  • Superoxide Dismutase / metabolism


  • Caffeic Acids
  • Protective Agents
  • Malondialdehyde
  • Ethambutol
  • Superoxide Dismutase
  • caffeic acid phenethyl ester
  • Phenylethyl Alcohol
  • Isoniazid