Department of Anesthesiology, Department of Neurosurgery, Department of Physical Medicine and Rehabilitation, Department of Biochemistry, Department of Neurology, Dicle University, Diyarbakir, Turkey.
Eur Rev Med Pharmacol Sci. 2013 Nov;17(22):2988-93.
Studies related to the use of various antioxidant and anti-inflammatory drugs to decrease the toxic side effects related to MTX have been carried out. However, since no medicine providing full protection against the side effects of MTX has been discovered, the discovery of new agents is required.
The aim of this study was to determine whether methotrexate (MTX) causes oxidative stress and an inflammatory response in sciatic nerve, as well as whether carvacrol (CAR) and pomegranate (POM) have protective effects against the resulting oxidative stress and inflammatory response.
32 adult male Wistar albino rats were used in the study. The animals were divided into 4 groups: Group C: the rats were not given any medication; Group MTX: On study day 2, the rats were given a single dose of 20 mg/kg MTX, administered intraperitoneally; Group MTX+CAR: On study day one, the rats were administered a single dose of 73 mg/kg CAR intraperitoneally. On study day two, a single dose of 20 mg/kg MTX was administered intraperitoneally; Group MTX+POM: For seven days starting from the study day one, rats were given 225 mg/kg POM extract once a day through orogastric gavage. On study day two, a single dose of 20 mg/kg MTX was administered intraperitoneally. All animals were sacrificed on the day eight. TOS, TAS, MDA, TNF-α and IL-1β levels were evaluated in the sciatic nerve tissue.
In comparison to the control group, a decrease in TAS levels and an increase in TOS, MDA, IL-1β and TNF-α levels were detected in the MTX group. Compared to the MTX group, the MTX+CAR group had a significant increase in TAS level and significant decreases in TOS, MDA, IL-1β and TNF-α levels. In comparison to the MTX group, the MTX+POM group had a significant decrease in MDA, IL-1β and TNF-α levels. When the MTX+CAR and MTX+POM groups were compared, the TNF-α level measured was lower in the MTX+CAR group.
In this work, we have shown that MTX causes a significant oxidative stress and inflammatory response in rats' sciatic nerve tissue and that CAR had an antioxidant effect in this system. Furthermore, we have proven, for the first time, that both CAR and POM decreased the pro-inflammatory response.
已经开展了多项研究，旨在使用各种抗氧化和抗炎药物来降低与 MTX 相关的毒性副作用。然而，由于尚未发现能够完全预防 MTX 副作用的药物，因此需要开发新的药物。
本研究旨在确定甲氨蝶呤 (MTX) 是否会导致坐骨神经发生氧化应激和炎症反应，以及香芹酚 (CAR) 和石榴 (POM) 是否具有针对由此产生的氧化应激和炎症反应的保护作用。
本研究使用了 32 只成年雄性 Wistar 白化大鼠。将动物分为 4 组：C 组：不给任何药物；MTX 组：在研究第 2 天，大鼠腹腔内单次给予 20mg/kg MTX；MTX+CAR 组：在研究第 1 天，大鼠腹腔内单次给予 73mg/kg CAR。在研究第 2 天，腹腔内单次给予 20mg/kg MTX；MTX+POM 组：从研究第 1 天开始，连续 7 天，每天通过灌胃给予 225mg/kg POM 提取物。在研究第 2 天，腹腔内单次给予 20mg/kg MTX。所有动物均在第 8 天处死。评估坐骨神经组织中的 TOS、TAS、MDA、TNF-α 和 IL-1β 水平。
与对照组相比，MTX 组的 TAS 水平降低，TOS、MDA、IL-1β 和 TNF-α 水平升高。与 MTX 组相比，MTX+CAR 组的 TAS 水平显著升高，TOS、MDA、IL-1β 和 TNF-α 水平显著降低。与 MTX 组相比，MTX+POM 组 MDA、IL-1β 和 TNF-α 水平显著降低。与 MTX+CAR 和 MTX+POM 组相比，MTX+CAR 组 TNF-α 水平较低。
在这项工作中，我们表明 MTX 导致大鼠坐骨神经组织发生明显的氧化应激和炎症反应，而 CAR 在该系统中具有抗氧化作用。此外，我们首次证明，CAR 和 POM 均可降低促炎反应。
