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的细胞毒性、遗传毒性和有丝分裂毒性的体外研究。

The cytotoxic, genotoxic and mitotoxic effects of extract in vitro.

机构信息

Department of Biology, Faculty of Nature and Life Sciences and Earth and Universe Sciences, Université 8 Mai 1945, Guelma, Algeria.

Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Ege University, 35040 Bornova-İzmir, Turkey.

出版信息

Afr Health Sci. 2024 Mar;24(1):295-306. doi: 10.4314/ahs.v24i1.35.

Abstract

BACKGROUND

The Mediterranean thistle L. (Asteraceae; AG) has diterpenoid glucosides; atractyloside and carboxyatractyloside that interact with mitochondrial protein adenine nucleotide translocator (ANT) and resulted in ATP inhibition. Despite its well-known toxicity, acute poisonings still occur with this plant. Although most symptoms are attributed to ANT and diterpenoids interaction, in-depth investigation of the effects of AG extract on various cellular processes has not been performed.

OBJECTIVE/METHOD: We tested induction of mitochondrial permeability transition pore (MPTP) opening in bovine liver mitochondria and evaluated its cytotoxicity and genotoxicity using test. Cell division, mitotic index (MI) and total chromosomal and mitotic aberrations (TAs), that all seem potentially affected by ATP shortage, were studied in root cells of exposed to extract.

RESULTS

With the two different doses of two purified AG fractions, stronger induction of MPTP was observed compared to the induction with the standard pure atracyloside. Aqueous AG extract exerted inhibition root growth in at 6 different doses. The TAs was increased in a dose-dependent manner too, while mitotic index was decreased at the same doses. Evaluation of mitotic phases revealed mitodepressive effect of AG on roots.

CONCLUSION

this work highlights cellular and mitochondrial adverse effects of extracts. A purified fraction that likely corresponds to ATR derivatives induces MPTP opening leading to swelling of mitochondria and its dysfunction. test provides the evidence for genotoxicity and cytotoxicity.

摘要

背景

地中海蓟 L.(菊科;AG)含有二萜糖苷;千里光苷和羧基千里光苷,与线粒体蛋白腺嘌呤核苷酸转运蛋白(ANT)相互作用,导致 ATP 抑制。尽管它具有众所周知的毒性,但这种植物仍会发生急性中毒。尽管大多数症状归因于 ANT 和二萜的相互作用,但对 AG 提取物对各种细胞过程的影响尚未进行深入研究。

目的/方法:我们测试了牛肝线粒体中诱导线粒体通透性转换孔(MPTP)开放的情况,并使用彗星试验评估了其细胞毒性和遗传毒性。在暴露于 AG 提取物的根细胞中,研究了细胞分裂、有丝分裂指数(MI)和总染色体和有丝分裂异常(TAs),所有这些似乎都受到 ATP 短缺的潜在影响。

结果

用两种不同剂量的两种纯化的 AG 馏分,与标准的纯千里光苷相比,观察到更强的 MPTP 诱导作用。水提 AG 提取物在 6 种不同剂量下抑制根的生长。TAs 也呈剂量依赖性增加,而有丝分裂指数在相同剂量下降低。对有丝分裂阶段的评估显示 AG 对 根有促有丝分裂作用。

结论

这项工作强调了 AG 提取物对细胞和线粒体的不良影响。一种可能对应于 ATR 衍生物的纯化馏分诱导 MPTP 开放,导致线粒体肿胀和功能障碍。彗星试验为遗传毒性和细胞毒性提供了证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b51/11217825/4ad7d2221749/AFHS2401-0295Fig1.jpg

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