Effect of low- and high-dose methotrexate on wound healing in rats.

Acta cirurgica brasileira Pub Date : 2025-03-14 eCollection Date: 2025-01-01 DOI:10.1590/acb403225
Abdullah Karasu, Yağmur Kuşcu, Caner Kayikci, Serkan Yildirim, Oğuzhan Kuşcu, Metin Kiliçlioğlu
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Abstract

Purpose: To investigate the effect of intraperitoneal treatment with low- and high-dose methotrexate (MTX) on wound healing in rats.

Methods: The study sample consisted of 54 healthy rats. Under aseptic conditions, skin wounds were created with two circular full-thickness punch tools, 10 mm in diameter, one on the right and the other one on the left of the dorsal vertebral line. The rats were randomly assigned to one of three main treatment groups. On the 0th day (2 hours before wound creation), 7th day, and 14th day, the control group received 0.3-mL saline, the low-MTX group received 3 mg/kg MTX, and the high-MTX group received 30 mg/kg MTX, all administered intraperitoneally. The wounds were evaluated seven, 14, and 21 days after injury through morphometrical, biochemical, histopathological, and immunohistochemical analyses.

Results: MTX dose-dependently decreased the degree of inflammation and angiogenesis, tissue hydroxyproline level, and HSP70 and tumor necrosis factor-α expression in the early phase of wound healing. It also suppressed epithelialization and collagen 1 expression throughout the wound-healing process.

Conclusion: The wounds treated with high-dose of MTX had statistically delayed wound closure on days 7, 14 and 21 compared to the saline group, while wounds treated with low-dose of MTX only had statistically delayed wound closure on day 14. In addition, weight loss was observed in rats treated with high-dose MTX, which was thought to reflect its toxicity. The dose-dependent adverse effect of MTX on wound healing may be due to its antiproliferative, antifibrotic, anti-inflammatory, and antiangiogenic effects.

低、高剂量甲氨蝶呤对大鼠创面愈合的影响。
目的:探讨低、高剂量甲氨蝶呤(MTX)腹腔注射对大鼠创面愈合的影响。方法:选取健康大鼠54只。在无菌条件下,用两个直径为10mm的圆形全厚度冲孔工具在椎背线的右侧和左侧制造皮肤伤口。这些大鼠被随机分配到三个主要治疗组之一。第0天(创面前2小时)、第7天和第14天,对照组给予生理盐水0.3 ml,低MTX组给予MTX 3 mg/kg,高MTX组给予MTX 30 mg/kg,均采用腹腔灌胃。分别于伤后7、14、21天进行形态学、生化、组织病理学和免疫组织化学分析。结果:MTX剂量依赖性地降低创面愈合早期炎症和血管生成程度、组织羟脯氨酸水平及HSP70和肿瘤坏死因子-α的表达。在整个伤口愈合过程中,它还能抑制上皮化和胶原蛋白1的表达。结论:与生理盐水组相比,高剂量MTX组创面愈合时间在第7、14、21天均有统计学延迟,而低剂量MTX组创面愈合时间仅在第14天有统计学延迟。此外,在大剂量MTX治疗的大鼠中观察到体重减轻,这被认为反映了其毒性。甲氨蝶呤对伤口愈合的剂量依赖性不良反应可能是由于其抗增殖、抗纤维化、抗炎和抗血管生成作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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