Ameliorating Role of Caffeic Acid Phenethyl Ester (CAPE) Against Methotrexate-Induced Oxidative Stress in the Sciatic Nerve, Spinal Cord and Brain Stem Tissues of Rats

Ertuğrul Uzar; Hasan Rıfat Koyuncuoğlu; H. Ramazan Yılmaz; Efkan Uz; Ahmet Songar; Onder Sahin; Vedat Ali Yurekli; Mustafa Yılmaz; Serkan Kılbaş; Süleyman Kutluhan

Ertuğrul Uzar¹, Hasan Rıfat Koyuncuoğlu¹, H. Ramazan Yılmaz², Efkan Uz², Ahmet Songar⁴, Onder Sahin³, Vedat Ali Yurekli¹, Mustafa Yılmaz¹, Serkan Kılbaş¹, Süleyman Kutluhan¹

¹Suleyman Demirel University, School Of Medicine Department Of Neurology, Isparta, Turkey
²Suleyman Demirel University, School Of Medicine Department Of Medical Biology And Genetics, Isparta, Turkey
³Afyon Kocatepe University, School Of Medicine, Department Of Anatomy, Afyonkarahisar, Turkey
⁴Namık Kemal Universisty, Scool Of Medicine Of Department Of Pathology, Tekirdag

Keywords: Caffeic acid phenethyl ester, methotrexate, oxidative stress, sciatic nerve, spinal cord.

Abstract

OBJECTIVE: Methotrexate (MTX)-associated neurotoxicity is an important clinical problem in cancer patients, but the mechanisms of

MTX-induced neurotoxicity are not yet known exactly. The aims of this study were (1) to investigate the possible role of malondialdehyde

(MDA), superoxide dismutase (SOD) enzyme, glutathione peroxidase (GSH-Px) and catalase (CAT) in the pathogenesis of

MTX-induced neurotoxicity and (2) to determine whether there is a putative protective effect of caffeic acid phenethyl ester (CAPE)

on MTX-induced neurotoxicity in the spinal cord, brainstem and sciatic nerve of rats.

METHODS: A total of 19 adult Wistar male rats were divided into three experimental groups. Group I, control group;

Group II, MTX-treated group; and Group III, MTX + CAPE-treated group. MTX was administered to the MTX and MTX + CAPE groups

intraperitoneally (IP) with a single dose of 20 mg/kg on the second day of the experiment. CAPE was administered to the MTX

+ CAPE group IP with a dose of 10 μmol/kg for 7 days.

RESULTS: In the sciatic nerve and spinal cord tissue, CAT and GSH-Px activities were increased in the MTX group in comparison with

the control group. CAPE treatment with MTX significantly decreased CAT and GSH-Px activities in the neuronal tissues of rats in comparison

with the MTX group. In the spinal cord and brainstem tissues, SOD activity in the MTX group was decreased in comparison

with the control group, but in the sciatic nerve, there was no significant difference. In the spinal cord and brainstem of rats, SOD activity

was increased in the CAPE + MTX group when compared with the MTX group. The level of MDA was higher in the MTX group

than in the control group. CAPE administration with MTX injection caused a significant decrease in MDA level when compared

with the MTX group.

CONCLUSION: These results reveal that MTX increases oxidative stress in the sciatic nerve, spinal cord and brainstem of rats and that

CAPE has a preventive effect on the oxidative stress via its antioxidant capacity.