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变叶木对卡莫司汀诱导雄性小鼠体细胞和生殖细胞遗传毒性的保护作用。

Protective role of Codiaeum variegatum against genotoxicity induced by carmustine in somatic and germ cells of male mice.

机构信息

Department of Genetics and Cytology, National Research Centre, Giza, 12622, Egypt.

Chemistry of Natural Compounds Department, National Research Centre, Giza, 12622, Egypt.

出版信息

Mol Biol Rep. 2022 Oct;49(10):9543-9553. doi: 10.1007/s11033-022-07845-9. Epub 2022 Sep 2.

Abstract

BACKGROUND

Carmustine (Cr) is an important chemotherapeutic drug, widely used in the treatment of brain tumors. Herein, the protective role of Codiaeum variegatum leaves ethyl acetate fraction was determined against genotoxicity of Cr. The technique HPLC-qTOF-MS/MS was used to identify the constituents in C. variegatum.

MATERIALS

90 male mice were used to evaluate micronuclei (MPCEs) in bone marrow, chromosomal aberration (CAs) in bone marrow and mouse spermatocytes, sperm abnormalities, and gene expression (qRT-PCR). The following groups were included, I: Negative control (ethanol 30%), II: Positive control (i.p injected once with 30 mg/kg Cr), III: Control orally treated with C. variegatum at 500 mg/kg, four days. IV-VI: treated with 100, 300, and 500 mg/kg of the plant (4 days) plus a single dose of Cr.

RESULTS

In bone marrow, Cr induced significant increase in MPCEs and CAs by 3 and 7-folds respectively over the control. Cr also induced a significant percentage of CAs in spermatocytes in meiosis in the form of univalent (X-Y and autosomal univalent) and also a significant percentage of morphological sperm abnormalities was recorded. A large number of coiled tail abnormalities were detected indicating the effect of Cr in sperm motility. Cr induced an overexpression of p53 gene. C. variegatum mitigated all deleterious genotoxic effects of Cr. Chemical analysis showed that flavones (35.21%) and phenolic acids (17.62%) constitute the main components.

CONCLUSIONS

The results indicated that Cr is genotoxic in both somatic and germ cells. The active components in C. variegatum together participate in the obtained protective role.

摘要

背景

卡莫司汀(Cr)是一种重要的化疗药物,广泛用于治疗脑肿瘤。本研究旨在确定变叶木叶片乙酸乙酯部位对 Cr 遗传毒性的保护作用。采用 HPLC-qTOF-MS/MS 技术鉴定变叶木中的成分。

材料

90 只雄性小鼠用于评估骨髓中的微核(MPCEs)、骨髓和小鼠精母细胞中的染色体畸变(CAs)、精子异常和基因表达(qRT-PCR)。包括以下组:I:阴性对照(30%乙醇);II:阳性对照(i.p 注射 30mg/kg Cr 一次);III:C. variegatum 以 500mg/kg 口服处理的对照组,连续 4 天;IV-VI:分别用 100、300 和 500mg/kg 植物(4 天)加一次 Cr 处理。

结果

骨髓中,Cr 诱导 MPCEs 和 CAs 分别比对照组增加 3 倍和 7 倍。Cr 还诱导减数分裂中期精母细胞中的单价(X-Y 和常染色体单价)出现显著比例的 CAs,也记录到显著比例的形态学精子异常。大量卷曲尾异常被检测到,表明 Cr 对精子活力有影响。Cr 诱导 p53 基因过度表达。变叶木减轻了 Cr 的所有有害遗传毒性作用。化学分析表明,黄酮类化合物(35.21%)和酚酸(17.62%)构成主要成分。

结论

Cr 对体细胞和生殖细胞均具有遗传毒性。变叶木中的活性成分共同参与获得的保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/308a/9515021/781d408c8921/11033_2022_7845_Fig1_HTML.jpg

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