Canagliflozin alleviates acetaminophen-induced renal and hepatic injury in mice by modulating the p-GSK3β/Fyn-kinase/Nrf-2 and p-AMPK-α/STAT-3/SOCS-3 pathways
Abstract Despite the fact that canagliflozin (Cana), a sodium-glucose cotransporter 2 inhibitor, is an anti-diabetic medication with additional effects on the kidney, there is limited experimental data to deliberate its hepato-reno-protective potentiality. Acetaminophen (APAP) overdose remains one o...
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| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-01-01
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| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-024-82163-7 |
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| Summary: | Abstract Despite the fact that canagliflozin (Cana), a sodium-glucose cotransporter 2 inhibitor, is an anti-diabetic medication with additional effects on the kidney, there is limited experimental data to deliberate its hepato-reno-protective potentiality. Acetaminophen (APAP) overdose remains one of the prominent contributors to hepato-renal damage. Aim: Our study assessed the novel effect of Cana against APAP-induced toxicities. Main methods: mice were randomized into five groups: negative control, Cana25, APAP, Cana10 + APAP, and Cana25 + APAP. Cana was given for 5 days; a single dose of APAP was injected on the 6th day, followed by the scarification of animals 24 h later. Key findings: Pre-treatment with Cana ameliorated hepatic and renal functions, whereas, on the molecular levels, Cana promoted hepatic/renal P-AMP-activated protein kinase-α/ protein kinase B (p-Akt)/Glycogen synthase kinase (p-GSK3β) protein expression. Alternatively, Cana dampened the expression of STAT-3 and Fyn-kinase genes with a subsequent increase in the contents of suppressor of cytokine signaling (SOCS)-3 and also boosted the contents of the nuclear factor erythroid related factor 2 (Nrf-2)/heme oxygenase (HO)-1/ NADPH quinone oxidoreductase (NQO)-1 axis. The crosstalk between these paths ameliorated the APAP-induced hepatorenal structural alterations. Significance: Cana hepatorenal protective impact was provoked partly through modulating p-AMPK-α /SOCS-3/STAT-3 and GSK3β/Fyn-kinase signaling for its anti-inflammatory and antioxidant effects. |
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| ISSN: | 2045-2322 |