Uzar Ertugrul, Koyuncuoglu Hasan Rifat, Uz Efkan, Yilmaz H Ramazan, Kutluhan Suleyman, Kilbas Serkan, Gultekin Fatih
School of Medicine Department of Neurology, Suleyman Demirel University, Isparta, Turkey.
Mol Cell Biochem. 2006 Oct;291(1-2):63-8. doi: 10.1007/s11010-006-9196-5. Epub 2006 May 23.
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 micromol 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.
甲氨蝶呤（MTX）是一种叶酸拮抗剂，被广泛用作细胞毒性化疗药物。MTX相关的神经毒性是一个重要的临床问题。本研究的目的是探讨咖啡酸苯乙酯（CAPE）对MTX诱导的大鼠小脑氧化应激的作用。总共19只成年雄性大鼠被分为以下三个实验组：MTX组（接受MTX治疗）、MTX + CAPE组（接受MTX + CAPE治疗）和对照组。在实验的第二天，MTX以20 mg kg⁻¹的单剂量腹腔注射（i.p.）。CAPE以10 μmol kg⁻¹ day⁻¹的剂量腹腔注射，持续7天。测定大鼠小脑组织中的丙二醛（MDA）水平以及超氧化物歧化酶（SOD）和过氧化氢酶（CAT）的活性。与对照组相比，MTX组的MDA水平（脂质过氧化的重要标志物）显著升高（p = 0.006）。与MTX组相比，MTX + CAPE组中CAPE显著降低了MTX诱导的脂质过氧化（p = 0.007）。与对照组相比，MTX组中SOD和CAT的活性显著增加（分别为p = 0.0001，p = 0.004）。CAPE处理显著降低了这些酶活性的增加（分别为p = 0.004，p = 0.034）。结果表明，CAPE可能保护大鼠小脑免受MTX治疗引起的氧化损伤。
