The Activities of Antioxidant Enzymes and the Level of Malondialdehyde in Cerebellum of Rats Subjected to Methotrexate: Protective Effect of Caffeic Acid Phenethyl Ester
- 201 Downloads
Methotrexate (MTX), a folic acid antagonist, is widely used as a cytotoxic chemotherapeutic agent. MTX-associated neurotoxicity is an important clinical problem. The aim of this study was to investigate the role of caffeic acid phenethyl ester (CAPE) on cerebellar oxidative stress induced by MTX in rats. A total of 19 adult male rats were divided into three experimental groups as follows: MTX group (MTX treated), MTX+CAPE group (MTX+CAPE treated), and control group. MTX was administered intraperitoneally (i.p.) with a single dose of 20 mg kg−1 on the second day of experiment. CAPE was administered i.p. with a dose of 10 μmol kg−1 day−1 for 7 days. Malondialdehyde (MDA) levels and activities of superoxide dismutase (SOD) and catalase (CAT) were determined in cerebellar tissue of rats. MTX caused to significant increase in MDA levels (an important marker of lipid peroxidation) in the MTX group compared with the controls (p = 0.006). CAPE significantly reduced the MTX induced lipid peroxidation in the MTX+CAPE group compared to the MTX (p = 0.007). The activities of SOD and CAT were significantly increased in the MTX group when compared with the control group (p = 0.0001, p = 0.004, respectively). The increased activities of these enzymes were significantly reduced by CAPE treatment (p = 0.004, p = 0.034, respectively). As a result, CAPE may protect from oxidative damage caused by MTX treatment in rat cerebellum.
Keywordscaffeic acid phenethyl ester methotrexate malondialdehyde superoxide dismutase catalase cerebellum
Unable to display preview. Download preview PDF.
- 1.Mahoney DH Jr, Shuster JJ, Nitschke R, Lauer SJ, Steuber CP, Winick N, Camitta B: Acute neurotoxicity in children with B-precursor acute lymphoid leukemia: An association with intermediate-dose intravenous methotrexate and intrathecal triple therapy: A Pediatric Oncology Group study. J Clin Oncol 16: 1712–1722, 1998PubMedGoogle Scholar
- 4.Uzar E, Sahin O, Koyuncuoglu HR, Uz E, Bas O, Kilbas S, Yilmaz HR, Yurekli VA, Kucuker H, Songur A: The activity of adenosine deaminase and the level of nitric oxide in spinal cord of methotrexate administered rats: Protective effect of caffeic acid phenethyl ester. Toxicology 218(2/3): 125–133, 2006CrossRefPubMedGoogle Scholar
- 31.Michaluart P, Masferrer JL, Carothers AM, Subbaramaiah K, Zweifel BS, Koboldt C, Mestre JR, Grunberger D, Sacks PG, Tanabe T, Dannenberg AJ: Inhibitory effects of caffeic acid phenethyl ester on the activity and expression of cyclooxygenase-2 in human oral epithelial cells and in a rat model of inflammation. Cancer Res 59: 2347–2352, 1999PubMedGoogle Scholar
- 35.Lowry OH, Rosebrough NJ, Farr AL, Randall RJ: Protein measurement with the folin phenol reagent. J Clin Chem 193: 265–75, 1951Google Scholar