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聚乙二醇(PEG)3350 对甲氨蝶呤诱导的肝毒性模型的抗纤维化预防作用。

Antifibrotic preventive effect of polyethylene glycol (PEG) 3350 in methotrexateinduced hepatoxicity model.

机构信息

MD. Izmir Atatürk Training and Research Hospital - Department of Emergency Medicine - Izmir, Turkey.

MD. Ödemiş State Hospital - Department of Emergency Medicine - İzmir, Turkey.

出版信息

Acta Cir Bras. 2022 Jul 22;37(5):e370507. doi: 10.1590/acb370507. eCollection 2022.

Abstract

PURPOSE

Liver damage caused by drugs and other chemicals accounts for about 5% of all cases. Methotrexate (MTX), a folic acid analogue, is a first-line synthetic antimetabolite agent routinely used in the treatment of rheumatoid arthritis and other autoimmune and chronic inflammatory diseases. Polyethylene glycol (PEG) has antioxidant activity. In this study, we evaluated biochemically and histopathologically the antifibrotic effect of PEG 3350 administered intraperitoneally to prevent methotrexate-induced liver damage in rats.

METHODS

A total of 30 male rats including 10 rats was given no drugs (normal group), and 20 rats received single-dose 20 mg/kg MTXfor induced liver injury in this study. MTX was given to 20 rats, which were divided in two groups. Group 1 rats was given PEG30 mg/kg/day (Merck) intraperitoneally, and Group 2 rats % 0.9 NaCl saline 1 mL/kg/day intraperitoneally daily for two weeks.

RESULTS

Transforming growth factor beta (TGF-β), plasma malondialdehyde (MDA), liver MDA, serum tumour necrosis factor alpha (TNF-α), alanine aminotransferase and plasma pentraxin-3 levels and, according to tissue histopathology, hepatocyte necrosis, fibrosis and cellular infiltration were significantly better in MTX+PEG group than in MTX+saline group.

CONCLUSIONS

PEG 3350 is a hope for toxic hepatitis due to other causes, since liver damage occurs through oxidative stress and cell damage, similar to all toxic drugs.

摘要

目的

药物和其他化学物质引起的肝损伤约占所有病例的 5%。甲氨蝶呤(MTX)是一种叶酸类似物,是一种常用的一线合成抗代谢药物,用于治疗类风湿关节炎和其他自身免疫和慢性炎症性疾病。聚乙二醇(PEG)具有抗氧化活性。在这项研究中,我们评估了聚乙二醇 3350 经腹腔给药预防大鼠甲氨蝶呤诱导的肝损伤的抗纤维化作用的生化和组织病理学。

方法

共 30 只雄性大鼠,其中 10 只大鼠未给予药物(正常组),20 只大鼠接受单次 20mg/kg MTX 诱导肝损伤。将 MTX 给予 20 只大鼠,分为两组。第 1 组大鼠每天腹腔给予 30mg/kg PEG(默克),第 2 组大鼠每天腹腔给予 1ml/kg 0.9%生理盐水。

结果

转化生长因子-β(TGF-β)、血浆丙二醛(MDA)、肝 MDA、血清肿瘤坏死因子-α(TNF-α)、丙氨酸氨基转移酶和血浆 pentraxin-3 水平,以及组织病理学显示,MTX+PEG 组的肝细胞坏死、纤维化和细胞浸润均明显优于 MTX+生理盐水组。

结论

PEG 3350 是其他原因引起的中毒性肝炎的一种希望,因为肝损伤是通过氧化应激和细胞损伤引起的,与所有毒性药物相似。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b96/9323303/652c55f5091a/1678-2674-acb-37-5-e370407-gf01.jpg

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