Abstract: PO0358
Metabolomics Reveals the Efficacy of Limonin on Mitigating Cisplatin-Induced AKI
Session Information
- AKI: Mechanisms of Injury
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Zeng, Xi, State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, Gaungdong, China
- Zhou, Xianke, State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, Gaungdong, China
- Xiang, Yadie, State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, Gaungdong, China
- Chen, Yudan, State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, Gaungdong, China
- Fu, Haiyan, State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, Gaungdong, China
Background
In the clinic, acute kidney injury (AKI) is one of the most severe cisplatin side effects, limiting its use in cancer therapy. Our previous study demonstrated that Limonin, a triterpenoid compound extracted from citrus, alleviated cisplatin-induced AKI. However, the involved mechanisms remain largely unknown. In this study, we elucidated how Limonin mitigates cisplatin-induced AKI from a new perspective, metabolomics.
Methods
A total of 30 mice were divided into three groups: Sham, Cisplatin + vehicle, and Cisplatin + Limonin. Limonin was administrated once daily via oral gavage started 3 days before cisplatin injection. At 72 h after cisplatin injection, kidney tissues were collected for metabolomics. Metabolomics was performed using Trace 1310 Gas Chromatograph equipped with an AS 1310 autosampler connected to a TSQ 8000 triple quadrupole mass spectrometer.
Results
After AKI, Limonin significantly preserved serum creatinine and blood urea nitrogen levels and ameliorated kidney tubular injury, compared with vehicles. Kidney samples were then subjected to metabolomics. A total of 302 metabolites were detected. The principal component analysis indicated that these metabolites could be well separated, reflecting the changes of metabolite distribution after treatment of Limonin. Multivariate statistical analysis further identified 34 endogenous differentially expressed metabolites within three groups. Intriguingly, phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, and linoleic acid metabolism were the top disturbed metabolic pathways amid the AKI repair process. These metabolic pathways are tightly correlated with oxidative stress, inflammatory response, and energy metabolism. Specifically, Limonin reduced Linoleic acid content, a major metabolite in the linoleic acid metabolism pathway in the AKI kidneys. Downregulation of Linoleic acid subsequently inhibited the synthesis of arachidonic acid. It ultimately influenced the abundance of metabolites in the tricarboxylic acid cycle to exhibit its protective role of Limonin in mitigating AKI.
Conclusion
Our data suggested that Limonin mitigates cisplatin-induced AKI through alternating multiple metabolic pathways.
Funding
- Government Support – Non-U.S.