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没食子酸可改善三氧化二砷诱导的肾毒性,涉及 NF-κB 和 Nrf2 途径。

Tannic acid ameliorates arsenic trioxide-induced nephrotoxicity, contribution of NF-κB and Nrf2 pathways.

机构信息

School of Basic Medicine, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei, China.

School of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei, China.

出版信息

Biomed Pharmacother. 2020 Jun;126:110047. doi: 10.1016/j.biopha.2020.110047. Epub 2020 Mar 5.

DOI:10.1016/j.biopha.2020.110047
PMID:32146384
Abstract

BACKGROUND AND PURPOSE

Tannic acid (TA), a group of polyphenolic compounds, has multiple anticancer, antimutagenic, antioxidant and anti-inflammatory activities. However, the effects of TA on arsenic trioxide (ATO)-induced nephrotoxicity are still relatively unknown. This study investigated the protective effects and potential mechanisms of TA on ATO-induced nephrotoxicity in rats.

METHODS

Rats were intragastrically administered TA with concurrent ATO infused intraperitoneally over 10 days. Renal morphology changes were observed through light microscopy. The levels of antioxidants and pro-inflammatory factors were measured in the serum and renal tissue, respectively. Further, expression of B-cell lymphoma-2, B-cell lymphoma-extra large, p53, and Bcl-2-associated X protein were measured using an immunohistochemical method. The protein expression of nuclear factor kappa B (NF-κB), nuclear factor-erythroid-2-related factor 2 (Nrf2), and kelch-like ECH-associated protein 1 (Keap1) were measured by Western blot.

RESULTS

The data showed that ATO exposure significantly increased the serum nephritic, oxidative stress, apoptosis and inflammatory markers in the renal tissue of rats. Conversely, pretreatment with TA reversed these changes. Furthermore, TA treatment caused a significant decrease in NF-κB expression (P < 0.05), while increasing Nrf2 and Keap1 expressions (P < 0.05).

CONCLUSION

TA ameliorates ATO-induced nephrotoxicity, which is related to the inhibition of oxidative stress, inflammation and apoptosis, potentially through the NF-κB/Nrf2 pathway.

摘要

背景与目的

单宁酸(TA)是一类多酚化合物,具有多种抗癌、抗突变、抗氧化和抗炎活性。然而,TA 对三氧化二砷(ATO)诱导的肾毒性的影响尚不清楚。本研究探讨了 TA 对 ATO 诱导的大鼠肾毒性的保护作用及其潜在机制。

方法

大鼠连续 10 天腹腔内注射 ATO 并同时灌胃 TA。通过光镜观察肾形态变化。分别检测血清和肾组织中的抗氧化剂和促炎因子水平。进一步采用免疫组化法检测 B 细胞淋巴瘤-2、B 细胞淋巴瘤-extra large、p53 和 Bcl-2 相关 X 蛋白的表达。采用 Western blot 法检测核因子 kappa B(NF-κB)、核因子-红细胞 2 相关因子 2(Nrf2)和 Kelch 样 ECH 相关蛋白 1(Keap1)的蛋白表达。

结果

数据显示,ATO 暴露显著增加了大鼠肾组织中的血清肾炎、氧化应激、凋亡和炎症标志物。相反,TA 预处理逆转了这些变化。此外,TA 处理导致 NF-κB 表达显著降低(P < 0.05),同时增加了 Nrf2 和 Keap1 的表达(P < 0.05)。

结论

TA 改善了 ATO 诱导的肾毒性,这与抑制氧化应激、炎症和凋亡有关,可能通过 NF-κB/Nrf2 通路。

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