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莪术醇通过下调 MAPK 和 NF-κB 通路减轻顺铂诱导的小鼠急性肾损伤。

Ojeoksan Ameliorates Cisplatin-Induced Acute Kidney Injury in Mice by Downregulating MAPK and NF-κB Pathways.

机构信息

Hanbang Cardio-Renal Syndrome Research Center, School of Korean Medicine, Wonkwang University, Iksan 54538, Korea.

Department of Pharmacology, School of Korean Medicine, Wonkwang University, Iksan 54538, Korea.

出版信息

Int J Mol Sci. 2022 Oct 14;23(20):12254. doi: 10.3390/ijms232012254.

Abstract

Acute kidney injury (AKI) is a major side effect of cisplatin, a crucial anticancer agent. Therefore, it is necessary to develop drugs to protect against cisplatin-induced nephrotoxicity. Ojeoksan (OJS), a traditional blended herbal prescription, is mostly used in Korea; however, there are no reports on the efficacy of OJS against cisplatin-induced AKI. To investigate the reno-protective effect of OJS on AKI, we orally administered 50, 100, and 200 mg/kg of OJS to mice 1 h before intraperitoneal injection with 20 mg/kg of cisplatin. OJS inhibited the increase of blood urea nitrogen (BUN) and serum creatinine (SCr) levels and reduced histological changes in the kidney, like loss of brush borders, renal tubular necrosis, and cast formation. Administration of OSJ reduced the levels of pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α. In addition, OJS inhibited the mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) pathways in cisplatin-induced AKI. These results suggest that OJS attenuates cisplatin-induced AKI by downregulating the MAPK and NF-κB pathways.

摘要

急性肾损伤 (AKI) 是顺铂这种重要抗癌药物的一个主要副作用。因此,有必要开发药物来预防顺铂引起的肾毒性。莪术(OJS)是一种传统的混合草药处方,主要在韩国使用;然而,目前尚无关于 OJS 对顺铂诱导的 AKI 疗效的报告。为了研究 OJS 对 AKI 的肾保护作用,我们在给小鼠腹腔注射 20mg/kg 顺铂前 1 小时,口服给予 50、100 和 200mg/kg 的 OJS。OJS 抑制了血尿素氮 (BUN) 和血清肌酐 (SCr) 水平的升高,并减轻了肾脏的组织学变化,如刷状缘丢失、肾小管坏死和铸型形成。OJS 还降低了促炎细胞因子(如白细胞介素 (IL)-1β、IL-6 和肿瘤坏死因子 (TNF)-α)的水平。此外,OJS 抑制了顺铂诱导的 AKI 中丝裂原活化蛋白激酶 (MAPK) 和核因子 kappa B (NF-κB) 途径。这些结果表明,OJS 通过下调 MAPK 和 NF-κB 途径来减轻顺铂诱导的 AKI。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4b1/9603434/756caae22a97/ijms-23-12254-g001.jpg

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