Isoliquiritin Ameliorates Cisplatin-Induced Renal Proximal Tubular Cell Injury by Antagonizing Apoptosis, Oxidative Stress and Inflammation

Zhiyin Pei; Meng Wu; Hanqing Yu; Guangfeng Long; Zhen Gui; Xiaonan Li; Hongbing Chen; Zhanjun Jia; Weiwei Xia

doi:10.3389/fmed.2022.873739

Isoliquiritin Ameliorates Cisplatin-Induced Renal Proximal Tubular Cell Injury by Antagonizing Apoptosis, Oxidative Stress and Inflammation

Front Med (Lausanne). 2022 Mar 30:9:873739. doi: 10.3389/fmed.2022.873739. eCollection 2022.

Authors

Zhiyin Pei¹, Meng Wu¹, Hanqing Yu¹, Guangfeng Long¹, Zhen Gui¹, Xiaonan Li², Hongbing Chen¹, Zhanjun Jia^{3

4

5}, Weiwei Xia^{1

3

4

5}

Affiliations

¹ Department of Clinical Laboratory, Children's Hospital of Nanjing Medical University, Nanjing, China.
² Department of Children Health Care, Children's Hospital of Nanjing Medical University, Nanjing, China.
³ Department of Nephrology, Children's Hospital of Nanjing Medical University, Nanjing, China.
⁴ Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing, China.
⁵ Nanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University, Nanjing, China.

Abstract

Acute kidney injury (AKI) is a clinical syndrome characterized by morbidity, mortality, and cost. Cis-diamminedichloroplatinum (cisplatin) is a chemotherapeutic agent used to treat solid tumors and hematological malignancies, but its side effects, especially nephrotoxicity, limit its clinical application. Isoliquiritin (ISL), one of the major flavonoid glycoside compounds in licorice, has been reported to have anti-apoptotic, antioxidant, and anti-inflammatory activities. However, the effect and mechanism of ISL on cisplatin-induced renal proximal tubular cell injury remain unknown. In this study, mouse proximal tubular cells (mPTCs) and human proximal tubule epithelial cells (HK2) were administered increasing concentrations of ISL from 7.8125 to 250 μM. Moreover, mPTC and HK2 cells were pretreated with ISL for 6-8 h, followed by stimulation with cisplatin for 24 h. CCK-8 assay was performed to evaluate the cell viability. Apoptosis and reactive oxygen species (ROS) of cells were measured by using flow cytometer and western blotting. Our results showed that ISL had no obvious effect on cell viability. ISL decreased cisplatin-induced cell injury in a dose-dependent manner. ISL also protected against cisplatin-induced cell apoptosis. Meanwhile, the enhanced protein levels of Bax, cleaved caspase-3/caspase-3 ratio, levels of Pp-65/p-65, levels of IL-6, and the production of ROS induced by cisplatin were significantly attenuated by ISL treatment. Moreover, ISL markedly increased the protein levels of Bcl-2 and SOD2, which were reduced by cisplatin stimulation. These results showed that ISL ameliorated cisplatin-induced renal proximal tubular cell injury by antagonizing apoptosis, oxidative stress and inflammation.

Keywords: apoptosis; cisplatin; inflammation; oxidative stress; renal proximal tubular cells.