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束缚应激减弱了褪黑素对二甲基苯并(a)蒽(DMBA)诱导致癌作用的抗氧化潜力。

Restraint stress abates the antioxidant potential of melatonin on dimethyl benz (a) anthracene (DMBA) induced carcinogenesis.

机构信息

Department of Biochemistry, Faculty of Life Sciences, AMU, Aligarh, 202002, India.

Department of Chemistry, University of Detroit Mercy, Detroit, MI, 48221, USA.

出版信息

Med Oncol. 2020 Sep 29;37(10):96. doi: 10.1007/s12032-020-01422-5.

Abstract

Free radical involvement in initiation, promotion and progression of carcinogenesis, implicates that scavengers of free radicals may act as inhibitors in the carcinogenic process. Melatonin, an antioxidant was used in the present study to evaluate its effectiveness on skin carcinogenesis induced by DMBA both with and without chronic restraint stress (CRS). Fifty Swiss albino young male rats were divided into five groups of 10 rats each as controls, topical DMB alone, Pre CRS-DMBA, melatonin DMBA and Pre-CRS-DMBA-melatonin treated groups. After 18 weeks blood was collected along with liver and skin samples. These were used for antioxidant enzyme assay, DNA damage and fluorescent spectra analysis. Melatonin showed antioxidant potential in combatting DMBA induced skin carcinogenesis measured by free radical scavenging enzymes and in vivo antioxidant status, DNA damage. Sensitive detection of the DMBA induced micro biochemical changes was possible by fluorescent spectroscopy from the transformed ratio of fluorescent intensity (F1 530 nm/630 nm) otherwise found constant for normal tissues. By melatonin treatment this ratio was similar to control values. The decreased antioxidant biochemical parameters depicting oxidative stress were comparable to comet assay and fluorescent studies, endorsing the chemo-preventive efficacy of melatonin against skin carcinogenesis caused by DMBA. CRS pre-exposure diminished the chemo-preventive/antioxidant ability of melatonin and the results were same as DMBA alone treatment, showing stress affected both cancer development and chemoprevention. CRS decreased the antioxidant potential of melatonin. Hence, managing stress could be perceived in cancer chemoprevention. Further studies focusing on stress reduction are needed.

摘要

自由基参与致癌作用的启动、促进和进展,这意味着自由基清除剂可能在致癌过程中作为抑制剂发挥作用。本研究采用抗氧化剂褪黑素来评估其对 1,2-二甲基苯蒽(DMBA)诱导的皮肤癌变的有效性,同时评估有无慢性束缚应激(CRS)的影响。将 50 只瑞士白化雄性幼鼠分为 5 组,每组 10 只,分别为对照组、单独给予 DMBA 组、CRS 前 DMBA 组、褪黑素 DMBA 组和 CRS 前 DMBA-褪黑素组。18 周后收集血液和肝脏、皮肤样本。这些样本用于抗氧化酶测定、DNA 损伤和荧光光谱分析。褪黑素通过清除自由基的酶和体内抗氧化状态、DNA 损伤,显示出对抗 DMBA 诱导的皮肤癌变的抗氧化潜力。通过荧光光谱,可以从荧光强度的比值(F1 530nm/630nm)检测到 DMBA 诱导的微生化变化,否则正常组织的该比值是恒定的。通过褪黑素处理,该比值与对照值相似。降低的抗氧化生物化学参数表明氧化应激,与彗星试验和荧光研究相当,证实了褪黑素对 DMBA 引起的皮肤癌变的化学预防作用。CRS 预先暴露降低了褪黑素的化学预防/抗氧化能力,结果与单独给予 DMBA 治疗相同,表明应激既影响癌症的发展,也影响化学预防。CRS 降低了褪黑素的抗氧化潜力。因此,在癌症化学预防中可以认为应激会影响癌症的发展。需要进一步研究集中在减轻压力上。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4283/7522450/04f42746235b/12032_2020_1422_Fig1_HTML.jpg

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