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

IF 2.1 4区 医学 Q3 CHEMISTRY, MULTIDISCIPLINARY Drug and Chemical Toxicology Pub Date : 2024-12-29 DOI:10.1080/01480545.2024.2442660
Ismail Aydin, Zuleyha Erisgin, Esma Cinar, M Zuhal Barak, Yavuz Tekelioglu, Murat Usta, Hasan Serdar Mutlu, Ismail Turkoglu
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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 (n = 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.

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甲氨蝶呤和辅酶q10联合使用是否应重新考虑脂肪变性?生化、流式细胞术、组织病理学实验研究。
在本研究中,我们研究了日常生活中广泛使用的辅酶Q10 (CoQ10)对甲氨蝶呤(MTX)诱导的肝毒性的影响,这是目前在恶性肿瘤和自身免疫性疾病中广泛使用的。24只雌性Wistar白化大鼠分为4组。组1 (n = 6)连续7 d灌胃玉米油1 mL。组2给予20 mg/kg腹腔注射。甲氨蝶呤只在实验第一天使用。3组患者给予20 mg/kg (i.p)。试验第1天给予MTX, 1 mL玉米油中溶辅酶q10 100 mg/kg灌胃7 d,第4组给予1 mL玉米油中溶辅酶q10 100 mg/kg灌胃7 d。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),马松三色和周期性酸希夫(PAS)染色切片进行组织病理学分析,流式细胞术进行凋亡分析(% Annexin V阳性),并对氧化应激标志物(GSH, CAT和TBARS)进行生化分析。组织病理学分析显示,MTX组细胞凋亡、退让、纤维化和炎症细胞浸润增加,而MTX + CoQ10组细胞凋亡、退让、纤维化和炎症细胞浸润明显减少。有趣的结果是,在MTX + CoQ10组中观察到脂肪变性和TBARS升高。因此,尽管CoQ10对MTX诱导的肝毒性具有保护作用,但MTX和CoQ10联合使用导致的脂肪变性还有待进一步研究。
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来源期刊
Drug and Chemical Toxicology
Drug and Chemical Toxicology 医学-毒理学
CiteScore
6.00
自引率
3.80%
发文量
99
审稿时长
3 months
期刊介绍: Drug and Chemical Toxicology publishes full-length research papers, review articles and short communications that encompass a broad spectrum of toxicological data surrounding risk assessment and harmful exposure. Manuscripts are considered according to their relevance to the journal. Topics include both descriptive and mechanics research that illustrates the risk assessment implications of exposure to toxic agents. Examples of suitable topics include toxicological studies, which are structural examinations on the effects of dose, metabolism, and statistical or mechanism-based approaches to risk assessment. New findings and methods, along with safety evaluations, are also acceptable. Special issues may be reserved to publish symposium summaries, reviews in toxicology, and overviews of the practical interpretation and application of toxicological data.
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