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单个及组合的杂色曲菌素和 5-甲氧基杂色曲菌素对大鼠肺脏的单次剂量毒性。

Single-Dose Toxicity of Individual and Combined Sterigmatocystin and 5-Methoxysterigmatocistin in Rat Lungs.

机构信息

Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia.

Institute for Medical Research and Occupational Health, 10000 Zagreb, Croatia.

出版信息

Toxins (Basel). 2020 Nov 23;12(11):734. doi: 10.3390/toxins12110734.

Abstract

Sterigmatocystin (STC) and 5-methoxysterigmatocystin (5-M-STC) are mycotoxins produced by common damp indoor Aspergilli series . Since both STC and 5-M-STC were found in the dust of indoor occupational and living areas, their occupants may be exposed to these mycotoxins, primarily by inhalation. Thus, STC and 5-M-STC were intratracheally instilled in male Wistar rats using doses (0.3 mg STC/kg of lung weight (l.w.); 3.6 mg 5-M-STC/kg l.w.; toxin combination 0.3 + 3.6 mg/kg l.w.) that corresponded to concentrations detected in the dust of damp indoor areas in order to explore cytotoxicity, vascular permeability, immunomodulation and genotoxicity. Single mycotoxins and their combinations insignificantly altered lactate-dehydrogenase activity, albumin, interleukin-6, tumor necrosis factor-α and chemokine macrophage inflammatory protein-1α concentrations, as measured by ELISA in bronchioalveolar lavage fluid upon 24 h of treatment. In an alkaline comet assay, both mycotoxins provoked a similar intensity of DNA damage in rat lungs, while in a neutral comet assay, only 5-M-STC evoked significant DNA damage. Hence, naturally occurring concentrations of individual STC may induce DNA damage in rat lungs, in which single DNA strand breaks prevail, while 5-M-STC was more responsible for double-strand breaks. In both versions of the comet assay treatment with STC + 5-M-STC, less DNA damage intensity occurred compared to single mycotoxin treatment, suggesting an antagonistic genotoxic action.

摘要

表型霉素(STC)和 5-甲氧基表型霉素(5-M-STC)是由常见的室内曲霉菌系列产生的真菌毒素。由于 STC 和 5-M-STC 都在室内职业和生活区域的灰尘中被发现,其居住者可能会通过吸入的方式暴露于这些真菌毒素。因此,使用相当于室内潮湿环境灰尘中检测到的浓度的剂量(0.3mg STC/kg 肺重(l.w.);3.6mg 5-M-STC/kg l.w.;毒素组合 0.3+3.6mg/kg l.w.),通过气管内滴注将 STC 和 5-M-STC 注入雄性 Wistar 大鼠体内,以探索细胞毒性、血管通透性、免疫调节和遗传毒性。单一真菌毒素及其组合对 24 小时处理后支气管肺泡灌洗液中的乳酸脱氢酶活性、白蛋白、白细胞介素-6、肿瘤坏死因子-α和趋化因子巨噬细胞炎性蛋白-1α浓度的影响,通过 ELISA 进行了测量,没有明显变化。在碱性彗星试验中,两种真菌毒素在大鼠肺部均引起类似强度的 DNA 损伤,而在中性彗星试验中,只有 5-M-STC 引起明显的 DNA 损伤。因此,自然存在的 STC 浓度可能会在大鼠肺部引起 DNA 损伤,其中单链 DNA 断裂占主导地位,而 5-M-STC 则更易导致双链断裂。在彗星试验的两种版本中,与单一真菌毒素处理相比,STC+5-M-STC 处理导致的 DNA 损伤强度较低,表明存在拮抗遗传毒性作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ccf/7700161/7975684dadab/toxins-12-00734-g001.jpg

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