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实验性脑肿瘤氧化应激的抗氧化反应中的性别差异。

Gender Differences in the Antioxidant Response to Oxidative Stress in Experimental Brain Tumors.

机构信息

Department of Health Sciences, Faculty of Health Sciences, University of Jaen, Jaen, Spain.

Department of Nursing, Faculty of Medicine and Nursing, University of Cordoba, Cordoba, Spain.

出版信息

Curr Cancer Drug Targets. 2019;19(8):641-654. doi: 10.2174/1568009618666181018162549.

DOI:10.2174/1568009618666181018162549
PMID:30338739
Abstract

BACKGROUND

Brain tumorigenesis is related to oxidative stress and a decreased response of antioxidant defense systems. As it is well known that gender differences exist in the incidence and survival rates of brain tumors, it is important to recognize and understand the ways in which their biology can differ.

OBJECTIVE

To analyze gender differences in redox status in animals with chemically-induced brain tumors.

METHODS

Oxidative stress parameters, non-enzyme and enzyme antioxidant defense systems are assayed in animals with brain tumors induced by transplacental N-ethyl-N-nitrosourea (ENU) administration. Both tissue and plasma were analyzed to know if key changes in redox imbalance involved in brain tumor development were reflected systemically and could be used as biomarkers of the disease.

RESULTS

Several oxidative stress parameters were modified in tumor tissue of male and female animals, changes that were not reflected at plasma level. Regarding antioxidant defense system, only glutathione (GSH) levels were decreased in both brain tumor tissue and plasma. Superoxide dismutase (SOD) and catalase (CAT) activities were decreased in brain tumor tissue of male and female animals, but plasma levels were only altered in male animals. However, different protein and mRNA expression patterns were found for both enzymes. On the contrary, glutathione peroxidase (GPx) activity showed increased levels in brain tumor tissue without gender differences, being protein and gene expression also increased in both males and female animals. However, these changes in GPx were not reflected at plasma level.

CONCLUSION

We conclude that brain tumorigenesis was related to oxidative stress and changes in brain enzyme and non-enzyme antioxidant defense systems with gender differences, whereas plasma did not reflect the main redox changes that occur at the brain level.

摘要

背景

脑肿瘤的发生与氧化应激和抗氧化防御系统反应能力下降有关。众所周知,脑肿瘤的发病率和存活率存在性别差异,因此认识和了解其生物学差异的方式非常重要。

目的

分析化学诱导脑肿瘤动物的氧化还原状态的性别差异。

方法

用胎盘内给予 N-乙基-N-亚硝脲(ENU)诱导动物脑肿瘤,检测氧化应激参数、非酶和酶抗氧化防御系统。分析组织和血浆,以了解涉及脑肿瘤发展的氧化还原失衡的关键变化是否全身性地反映出来,并可作为该疾病的生物标志物。

结果

肿瘤组织中的几种氧化应激参数在雄性和雌性动物中发生改变,而这些改变在血浆水平上并未反映出来。关于抗氧化防御系统,只有谷胱甘肽(GSH)水平在脑肿瘤组织和血浆中均降低。雄性和雌性动物的脑肿瘤组织中超氧化物歧化酶(SOD)和过氧化氢酶(CAT)活性降低,但只有雄性动物的血浆水平发生改变。然而,两种酶的蛋白和 mRNA 表达模式不同。相反,谷胱甘肽过氧化物酶(GPx)在脑肿瘤组织中的活性升高,没有性别差异,且雄性和雌性动物的蛋白和基因表达均增加。然而,GPx 的这些变化在血浆水平上没有反映出来。

结论

我们的结论是,脑肿瘤的发生与氧化应激以及脑酶和非酶抗氧化防御系统的变化有关,存在性别差异,而血浆未能反映出主要发生在脑水平的氧化还原变化。

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