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

IF 1.1 4区 医学 Q3 SURGERY
Acta cirurgica brasileira Pub Date : 2022-07-22 eCollection Date: 2022-01-01 DOI:10.1590/acb370507
Hüseyin Acar, Omay Sorgun, Güner Yurtseve, Ejder Saylav Bora, Oytun Erbaş
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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.

Abstract Image

聚乙二醇(PEG) 3350对甲氨蝶呤肝毒性模型的抗纤维化预防作用。
目的:药物和其他化学物质引起的肝损害约占所有病例的5%。甲氨蝶呤(MTX)是一种叶酸类似物,是一种一线合成抗代谢药物,常规用于治疗类风湿性关节炎和其他自身免疫性和慢性炎症性疾病。聚乙二醇(PEG)具有抗氧化活性。在本研究中,我们从生物化学和组织病理学角度评估了PEG 3350腹腔注射预防甲氨蝶呤引起的大鼠肝损伤的抗纤维化作用。方法:30只雄性大鼠,其中10只不给药(正常组),20只大鼠单次给药20 mg/kg mtx致肝损伤。20只大鼠给予甲氨蝶呤,分为两组。1组大鼠腹腔灌胃PEG30 mg/kg/d(默克),2组大鼠腹腔灌胃% 0.9 NaCl生理盐水1 mL/kg/d,连续2周。结果:MTX+PEG组大鼠血清中转化生长因子β (TGF-β)、血浆丙二醛(MDA)、肝脏MDA、血清肿瘤坏死因子α (TNF-α)、丙氨酸转氨酶、血浆戊霉素-3水平及肝细胞坏死、纤维化、细胞浸润均明显优于MTX+生理盐水组。结论:PEG 3350是治疗其他原因引起的中毒性肝炎的希望,因为肝损伤与所有毒性药物类似,是通过氧化应激和细胞损伤发生的。
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来源期刊
CiteScore
1.90
自引率
9.10%
发文量
60
审稿时长
3-8 weeks
期刊介绍: Information not localized
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