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白藜芦醇对萘诱导的小鼠氧化应激的保护作用。

Protective effect of resveratrol against naphthalene-induced oxidative stress in mice.

作者信息

Sehirli Ozer, Tozan Ayfer, Omurtag Gülden Z, Cetinel Sule, Contuk Gazi, Gedik Nursal, Sener Göksel

机构信息

Department of Pharmacology, Marmara University School of Pharmacy, Istanbul, Turkey.

出版信息

Ecotoxicol Environ Saf. 2008 Sep;71(1):301-8. doi: 10.1016/j.ecoenv.2007.08.023. Epub 2008 Feb 7.

Abstract

OBJECTIVE

This investigation confirms the role of free radicals in naphthalene-induced toxicity and elucidates the mechanism of resveratrol (RVT).

METHODS

Both male and female BALB-c mice were administered with naphthalene (100 mg/kg, i.p.) for 30 days, either along with saline or along with RVT (10mg/kg, orally). At the end of the experiment, following treatment and sacrifice of animals by decapitation, lung, liver and kidney tissue samples were taken for histological examination or determination of malondialdehyde (MDA), glutathione (GSH), myeloperoxidase (MPO) activity and collagen contents. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN) and creatinine levels and lactate dehydrogenase (LDH) activity were measured in the serum samples, while TNF-alpha, IL-beta, IL-6 and total antioxidant capacity (AOC) were assayed in plasma samples.

RESULTS

Naphthalene administration caused a significant decrease in tissue GSH and plasma AOC, which was accompanied with significant increases in tissue MDA and collagen levels and MPO activity. Moreover, the pro-inflammatory mediators (TNF-alpha, IL-beta, IL-6), LDH activity, AST, ALT, creatinine and BUN levels were significantly increased in the naphthalene group. On the other hand, RVT treatment reversed all these biochemical indices as well as histopathological alterations induced by naphthalene.

CONCLUSIONS

Oxidative mechanisms play an important role in naphthalene-induced tissue damage, and RVT, by inhibiting neutrophil infiltration, balancing oxidant-antioxidant status, and regulating the generation of inflammatory mediators, ameliorates oxidative organ injury due to naphthalene toxicity.

摘要

目的

本研究证实自由基在萘诱导的毒性中的作用,并阐明白藜芦醇(RVT)的作用机制。

方法

将雄性和雌性BALB-c小鼠腹腔注射萘(100mg/kg)30天,同时分别给予生理盐水或RVT(10mg/kg,口服)。实验结束时,经处理后断头处死动物,采集肺、肝和肾组织样本进行组织学检查,或测定丙二醛(MDA)、谷胱甘肽(GSH)、髓过氧化物酶(MPO)活性和胶原蛋白含量。测定血清样本中的天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)、血尿素氮(BUN)和肌酐水平以及乳酸脱氢酶(LDH)活性,同时测定血浆样本中的肿瘤坏死因子-α(TNF-α)、白细胞介素-β(IL-β)、白细胞介素-6和总抗氧化能力(AOC)。

结果

给予萘导致组织GSH和血浆AOC显著降低,同时组织MDA和胶原蛋白水平以及MPO活性显著升高。此外,萘组的促炎介质(TNF-α、IL-β、IL-6)、LDH活性、AST、ALT、肌酐和BUN水平显著升高。另一方面,RVT治疗逆转了所有这些生化指标以及萘诱导的组织病理学改变。

结论

氧化机制在萘诱导的组织损伤中起重要作用,RVT通过抑制中性粒细胞浸润、平衡氧化还原状态和调节炎症介质的产生,减轻萘毒性引起的氧化性器官损伤。

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