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

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.