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就脂肪变性而言,是否应重新考虑甲氨蝶呤(MTX)与辅酶Q10(CoQ10)的联合使用?一项生物化学、流式细胞术、组织病理学实验研究。

Should combined MTX and CoQ10 use be reconsidered in terms of steatosis? A biochemical, flow cytometry, histopathological experimental study.

作者信息

Aydin Ismail, Erisgin Zuleyha, Cinar Esma, Barak M Zuhal, Tekelioglu Yavuz, Usta Murat, Mutlu Hasan Serdar, Turkoglu Ismail

机构信息

Department of General Surgery, Faculty of Medicine, Giresun University, Giresun, Turkiye.

Department of Histology and Embryology, Faculty of Medicine, Giresun University, Giresun, Turkiye.

出版信息

Drug Chem Toxicol. 2025 Sep;48(5):1090-1103. doi: 10.1080/01480545.2024.2442660. Epub 2024 Dec 29.

Abstract

In the present study, the effects of coenzyme Q10 (CoQ10), which is widely used in daily life, on the methotrexate (MTX)-induced hepatotoxicity, which is widely used today in malignancies and autoimmune diseases, were examined. Twenty-four female Wistar albino rats were divided into four groups. The group 1 ( = 6) was given 1 mL corn oil by oral gavage (p.o.) during seven days. Group 2 was given 20 mg/kg intraperitoneal (i.p.) MTX only on the first day of the experiment. Group 3 was given 20 mg/kg (i.p.) MTX on the first day of the experiment and 100 mg/kg CoQ10 dissolved in 1 mL corn oil were given by oral gavage during seven days, and group 4 was given 100 mg/kg CoQ10 dissolved in 1 mL corn oil by oral gavage during seven days. At the end of experiment, all animals were euthanized under anesthesia. In the liver tissue, histopathologic analysis on the hematoxylin and eosin (H&E), Masson trichrome, and periodic acid Schiff (PAS) stained sections, apoptotic analysis (% Annexin V positivity) by flow cytometry, and biochemical analysis for oxidative stress markers (GSH, CAT, and TBARS) was performed. According to histopathological analysis, apoptosis, concession, fibrosis, and inflammatory cell infiltration increased in the MTX group and those results significantly decreased in the MTX + CoQ10 groups. As an interesting result, fatty degeneration and TBARS elevation were observed in the MTX + CoQ10 group. As a result, although CoQ10 has protective effects on MTX-induced hepatotoxicity, fatty degeneration due to the combined usage of MTX and CoQ10 should be investigated with further studies.

摘要

在本研究中,检测了日常生活中广泛使用的辅酶Q10(CoQ10)对如今在恶性肿瘤和自身免疫性疾病中广泛应用的甲氨蝶呤(MTX)诱导的肝毒性的影响。将24只雌性Wistar白化大鼠分为四组。第1组(n = 6)在7天内通过口服灌胃(p.o.)给予1 mL玉米油。第2组仅在实验的第一天腹腔注射(i.p.)20 mg/kg MTX。第3组在实验的第一天腹腔注射20 mg/kg MTX,并在7天内通过口服灌胃给予溶解于1 mL玉米油中的100 mg/kg CoQ10,第4组在7天内通过口服灌胃给予溶解于1 mL玉米油中的100 mg/kg CoQ10。实验结束时,所有动物在麻醉下安乐死。在肝组织中,对苏木精和伊红(H&E)、Masson三色和过碘酸希夫(PAS)染色切片进行组织病理学分析,通过流式细胞术进行凋亡分析(Annexin V阳性率),并对氧化应激标志物(GSH、CAT和TBARS)进行生化分析。根据组织病理学分析,MTX组的凋亡、坏死、纤维化和炎性细胞浸润增加,而在MTX + CoQ10组中这些结果显著降低。有趣的是,在MTX + CoQ10组中观察到脂肪变性和TBARS升高。结果表明,尽管CoQ10对MTX诱导的肝毒性有保护作用,但MTX与CoQ10联合使用导致的脂肪变性应通过进一步研究进行调查。

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