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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2025-01-01
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| author | Abeer Bishr Bassant M. El-Mokadem Asmaa A. Gomaa |
| author_facet | Abeer Bishr Bassant M. El-Mokadem Asmaa A. Gomaa |
| author_sort | Abeer Bishr |
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| description | 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. |
| format | Article |
| id | doaj-art-3db13314c0194b859e484a34c7540904 |
| institution | Kabale University |
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| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-3db13314c0194b859e484a34c75409042025-01-05T12:23:29ZengNature PortfolioScientific Reports2045-23222025-01-0115111410.1038/s41598-024-82163-7Canagliflozin 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 pathwaysAbeer Bishr0Bassant M. El-Mokadem1Asmaa A. Gomaa2Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ahram Canadian UniversityDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Egyptian Chinese UniversityDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Ahram Canadian UniversityAbstract 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.https://doi.org/10.1038/s41598-024-82163-7AcetaminophenCanagliflozinNephrotoxicityHepatotoxicityp-AMPK-αFyn-kinase |
| spellingShingle | Abeer Bishr Bassant M. El-Mokadem Asmaa A. Gomaa 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 Scientific Reports Acetaminophen Canagliflozin Nephrotoxicity Hepatotoxicity p-AMPK-α Fyn-kinase |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | Acetaminophen Canagliflozin Nephrotoxicity Hepatotoxicity p-AMPK-α Fyn-kinase |
| url | https://doi.org/10.1038/s41598-024-82163-7 |
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