Short-term medication of dapagliflozin exacerbates CCl<inf>4</inf> induced acute liver injury

Tuo HAN; Ying LI; Lixia WANG; Yang XU; Jing JI; Yiwen WANG; Cheng LI; Chunyan ZHANG; Yan ZHANG; Yongqin LI; Congxia WANG

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Short-term medication of dapagliflozin exacerbates CCl4 induced acute liver injury

VernacularTitle:短期使用达格列净加重CCl4诱导的急性肝损伤
Author: Tuo HAN ¹ ; Ying LI ¹ ; Lixia WANG ¹ ; Yang XU ² ; Jing JI ² ; Yiwen WANG ¹ ; Cheng LI ¹ ; Chunyan ZHANG ¹ ; Yan ZHANG ¹ ; Yongqin LI ¹ ; Congxia WANG ¹
Author Information

1. Department of Cardiology,The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004
2. Department of Clinical Laboratory, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China
Publication Type:Journal Article
Keywords: acute liver injury; dapagliflozin; macrophage polarization; oxidative stress; nuclear factor-κB
From: Journal of Xi'an Jiaotong University(Medical Sciences) 2023;44(2):195-201
CountryChina
Language:Chinese
Abstract: 【Objective】 To investigate the role and mechanism of dapagliflozin (Dapa), a sodium glucose co-transporter 2 inhibitor, in acute liver injury. 【Methods】 Eight-week-old C57BL6/J mice were given a single intraperitoneal injection of CCl4 to induce acute liver injury. The mice were preventively given 5 mg/kg Dapa by gavage 24 h and 2 h before CCl4 injection, while those in the control group were given an equal volume of solvent gavage. After 24 h, the mice were anesthetized and sacrificed. H&E staining, plasma biochemistry, RT-qPCR, and Western blotting were used to detect the severity of liver injury and the expressions of macrophage-related genes. 【Results】 In the CCl4 group, hepatic infiltration of inflammatory cells increased, and liver and renal functions significantly deteriorated, which was further aggravated by Dapa. CCl4 could promote the expressions of M1 macrophages and fibrosis-related genes in the liver, but reduce those of M2 and antioxidant-related genes, and the latter was further inhibited by Dapa. In addition, the protein expression of arginase 1 decreased and that of SGLT2 increased after Dapa intervention, while NF-κB pathway did not change significantly, suggesting that Dapa might directly affect the energy metabolism homeostasis in the liver and aggravate acute liver injury induced by CCl4. 【Conclusion】 Dapa can exacerbate hepatic and renal damage in acute stage of liver injury, inhibit macrophages M2 polarization, and aggravate oxidative stress and inflammatory injury induced by CCl4.