评估水合吗啉作为一种肾脏保护剂对甲氨蝶呤诱导的肾毒性大鼠的作用。

IF 2.1 4区 医学 Q3 CHEMISTRY, MULTIDISCIPLINARY Drug and Chemical Toxicology Pub Date : 2024-11-27 DOI:10.1080/01480545.2024.2429616
Ekrem Darendelioğlu, Sevda Sağ, Cuneyt Caglayan
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引用次数: 0

摘要

甲氨蝶呤(MTX)是治疗大多数癌症的常用化疗药物。水合吗啉是一种强效抗氧化剂,是无花果、白桑葚等多种植物中的次生代谢产物。本研究的假设是,水合吗啉可通过提高抗氧化酶活性和抑制细胞凋亡过程,有效减轻 MTX 引起的大鼠肾损伤。本研究使用了 35 只雄性 Wistar 白化大鼠,并设立了五个不同的实验组,每组 7 只。第 1 组为对照组,第 2 组只口服吗啉(剂量为 100 毫克/千克)。第 3 组则只服用 MTX(剂量为 20 毫克/千克)。第 4 组混合使用 MTX(20 毫克/千克)和吗啉(50 毫克/千克),第 5 组混合使用 MTX(20 毫克/千克)和吗啉(100 毫克/千克)。与对照组相比,MTX 组的肾脏生物标志物(包括血清尿素、肌酐和脂质过氧化生物标志物 MDA)显著增加,抗氧化酶活性(SOD、CAT、GPx)和 GSH 水平明显下降。此外,MTX 还显著降低了 procas-3、Bcl-2、procas-9 和 procas-8 的表达,同时增加了 CYT-C 和 Bax 等凋亡基因的表达。以 50 毫克/千克和 100 毫克/千克的剂量同时服用吗啉水合物和 MTX,可有效控制氧化损伤水平和凋亡标志物,显示出抗氧化和抗凋亡特性。值得注意的是,与 50 毫克/千克的剂量相比,100 毫克/千克的剂量能提供更强的保护作用,这表明疗效与剂量有关。因此,这项研究支持以下结论:两种剂量水平的水合吗啉都能有效减轻 MTX 引起的肾损伤。
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Assessment of morin hydrate as a renal protective agent in rats subjected to methotrexate-induced nephrotoxicity.

Methotrexate (MTX) is a generally applied chemotherapeutic medicine in most cancers treatment. Morin hydrate, a robust antioxidant, is a secondary metabolite observed in numerous plants, along with figs, white mulberries, and others. The hypothesis of this study is that morin hydrate can effectively reduce MTX-induced kidney injury in rats by increasing antioxidant enzyme activity and inhibiting apoptotic processes. This study, 35 male Wistar albino rats were used, and five different experimental groups, each consisting of 7 rats were established. Group 1 served as the control group while Group 2 received morin exclusively via oral administration (at a dose of 100 mg/kg). Group 3, however, was administered MTX exclusively (at a dose of 20 mg/kg). Group 4 received a combination of MTX (20 mg/kg) and morin (50 mg/kg), and Group 5 received a combination of MTX (20 mg/kg) and morin (100 mg/kg). The MTX group showed a significant increase in kidney biomarkers, including serum urea, creatinine, and the lipid peroxidation biomarker MDA, compared to the control group, along with a notable decrease in antioxidant enzyme activity (SOD, CAT, GPx) and GSH levels. Furthermore, MTX notably decreased the expression of procas-3, Bcl-2, procas-9, and procas-8 while concurrently increasing the expression of apoptotic genes such as CYT-C and Bax. Co-administration of morin hydrate with MTX at doses of 50 and 100 mg/kg effectively managed oxidative damage levels and apoptotic markers, demonstrating antioxidant and anti-apoptotic properties. Notably, the 100 mg/kg dose provided more robust protection than the 50 mg/kg dose, indicating a dose-dependent efficacy. This investigation thus supports the conclusion that morin hydrate, at both dosage levels, effectively mitigates MTX-induced renal damage.

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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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