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


CONCLUSIONS
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.
Department of Ophthalmology, Dicle University, School of Medicine, Diyarbakır, Turkey. dralparslansahin@gmail.com
Alparslan
A
Şahin
Abdullah
A
Kürşat Cingü
Savaş
S
Kaya
Gül
G
Türkcü
Şeyhmus
Ş
Arı
Osman
O
Evliyaoğlu
Yasin
Y
Çınar
Fatih Mehmet
FM
Türkcü
Harun
H
Yüksel
Mehmet
M
Murat
İhsan
İ
Çaça
Osman
O
Gökalp
D000818:Animals; D002109:Caffeic Acids / Q000008:administration & dosage*; D004977:Ethambutol / Q000008:administration & dosage / Q000009:adverse effects; D007538:Isoniazid / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009901:Optic Nerve Diseases / Q000139:chemically induced / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010626:Phenylethyl Alcohol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D020011:Protective Agents / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012164:Retinal Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000473:pathology; D013482:Superoxide Dismutase / Q000378:metabolism
D002109:Caffeic Acids; D020011:Protective Agents; D008315:Malondialdehyde; D004977:Ethambutol; D013482:Superoxide Dismutase; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol; D007538:Isoniazid