Methotrexate-induced renal oxidative stress in rats: the role of a novel antioxidant caffeic acid phenethyl ester

Abstract

The exact mechanisms of methotrexate-induced renal toxicity have not yet been determined. However, several hypotheses have been put forward, including oxidative stress. The aim of this study was to investigate the role of caffeic acid phenethyl ester (Caffeic Ester), a novel antioxidant, on methotrexate-induced renal oxidative stress in rats. Nineteen adult male rats were equally divided into three experimental groups as follows: control group, methotrexate-treated group, and methotrexate+Caffeic Ester-treated group. A single dose of methotrexate (20 mg/kg) was administered intraperitoneally (ip). Caffeic Ester (10 micromol/kg) was administered ip, once daily for seven days. Malondialdehyde (MDA) levels (an index of lipid peroxidation) were used as a marker of oxidative stress-induced renal injury. Similarly, the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were determined to evaluate the changes of antioxidant status in renal tissue. Methotrexate administration to control rats increased MDA levels (P<0.0001), but decreased SOD, CAT and GSH-Px activities in renal tissue (P<0.0001). Caffeic Ester+ methotrexate treatment caused a significant decrease in MDA levels (P<0.001), and caused an increase in SOD, CAT and GSH-Px activities when compared with methotrexate treatment alone (P<0.001, <0.05, <0.0001, respectively). In conclusion, methotrexate leads to a reduction in antioxidant enzymatic defense capacity and causes lipid peroxidation in renal tissue. Similarly, Caffeic Ester exhibits protective effects on methotrexate-induced renal oxidative impairment in rats.

Effects of Lycopene Alone or Combined with Melatonin on Methotrexate-Induced Nephrotoxicity in Rats

“…It was reported that 20 mg/kg dose of Mtx, used in this study, highly exceeds interval dose and can be accepted as high dose Mtx in human (Oktem et al, 2006;Cetinkaya et al, 2007;Abdel-Raheem and Khedr, 2014). Mtx treatment at high doses may cause renal failure (Abelson et al, 1983).…”

Protective effect of propolis on methotrexate-induced kidney injury in the rat

“…In another study in Wistar albino rats, the nephrotoxic effect of MTX was associated with lipid peroxidation and reduction in antioxidant enzymatic defense capacity. 21 In this study, CAPE prevented nephrotoxicity and this effect was attributed to its scavenging activity for ROS in the kidney tissue. Therefore, we suggest that propolis prevents MTX-induced nephrotoxicity with its antioxidant properties.…”

Silibinin attenuates methotrexate-induced pulmonary injury by targeting oxidative stress

“…The predominant manifestation of MTX-induced lung toxicity is pulmonary fibrosis (3). In addition to pulmonary fibrosis, MTX treatment has been associated with acute interstitial pneumonitis (4)(5)(6)(7)(8).…”