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鞣花酸作为一种潜在的抗氧化剂,可减轻甲氨蝶呤诱导的雄性大鼠肝毒性。

Ellagic acid as a potential antioxidant, alleviates methotrexate-induced hepatotoxicity in male rats.

作者信息

Mehrzadi Saeed, Mehrabani Mehrnaz, Malayeri Ali Reza, Bakhshayesh Masoumeh, Kalantari Heibatullah, Goudarzi Mehdi

机构信息

a Razi Drug Research Center , Iran University of Medical Sciences , Tehran , Iran.

b Physiology Research Center, Institute of Basic and Clinical Physiology Sciences , Kerman University of Medical Sciences , Kerman , Iran.

出版信息

Acta Chir Belg. 2019 Apr;119(2):69-77. doi: 10.1080/00015458.2018.1455419. Epub 2018 Mar 28.

Abstract

BACKGROUND

Hepatotoxicity is one of the most life-threatening side-effects of Methotrexate therapy. Former studies highlighted the significance of oxidative stress in promoting Methotrexate-induced hepatotoxicity (MIH). Hence, the current study investigated the protective effect of Ellagic acid (EA), a poly-phenolic antioxidant, against MIH.

METHODS

Twenty-eight male Wistar rats were grouped into four sets: group 1 (control), group 2 (injected intraperitoneally with 20 mg/kg of Methotrexate on the 9th day), group 3 (treated orally with 10 mg/kg/day of EA for 10 days and injected with Methotrexate on the 9th day) and group 4 (treated with EA for 10 days). Subsequently, biochemical and histopathological parameters were evaluated in serum samples and liver tissues.

RESULTS

Methotrexate significantly increased activities of aminotransferases and ALP enzymes as well as levels of oxidative stress parameters in liver tissue. Likewise, Methotrexate decreased hepatic reduced glutathione level and activities of antioxidant enzymes. EA pre-treatment markedly attenuated the activities of aminotransferases and ALP, levels of oxidative stress parameters and augmented activities of antioxidant enzymes. Similarly, the remarkable protective effect of EA on liver has been confirmed by histological examination.

CONCLUSION

In sum, the current study supports the hypothesis that EA may be used as a promising pre-therapy to prevent the MIH.

摘要

背景

肝毒性是甲氨蝶呤治疗最危及生命的副作用之一。既往研究强调氧化应激在促进甲氨蝶呤诱导的肝毒性(MIH)中的重要性。因此,本研究调查了多酚类抗氧化剂鞣花酸(EA)对MIH的保护作用。

方法

将28只雄性Wistar大鼠分为四组:第1组(对照组),第2组(在第9天腹腔注射20mg/kg甲氨蝶呤),第3组(口服10mg/kg/天的EA,持续10天,并在第9天注射甲氨蝶呤)和第4组(用EA治疗10天)。随后,对血清样本和肝组织中的生化和组织病理学参数进行评估。

结果

甲氨蝶呤显著增加了肝组织中转氨酶和碱性磷酸酶的活性以及氧化应激参数水平。同样,甲氨蝶呤降低了肝脏中还原型谷胱甘肽水平和抗氧化酶的活性。EA预处理显著减弱了转氨酶和碱性磷酸酶的活性、氧化应激参数水平,并增强了抗氧化酶的活性。同样,组织学检查证实了EA对肝脏具有显著的保护作用。

结论

总之,本研究支持EA可作为预防MIH的一种有前景的预处理方法这一假设。

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