Effect of Empagliflozin on Thioacetamide-Induced Liver Injury in Rats: Role of AMPK/SIRT-1/HIF-1α Pathway in Halting Liver Fibrosis
Hepatic fibrosis causes severe morbidity and death. No viable treatment can repair fibrosis and protect the liver until now. We intended to discover the empagliflozin’s (EMPA) hepatoprotective efficacy in thioacetamide (TAA)-induced hepatotoxicity by targeting AMPK/SIRT-1 activity and reducing HIF-1...
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MDPI AG
2022-10-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/11/11/2152 |
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| author | Marwan A. ElBaset Rana S. Salem Fairouz Ayman Nadeen Ayman Nooran Shaban Sherif M. Afifi Tuba Esatbeyoglu Mahmoud Abdelaziz Zahraa S. Elalfy |
| author_facet | Marwan A. ElBaset Rana S. Salem Fairouz Ayman Nadeen Ayman Nooran Shaban Sherif M. Afifi Tuba Esatbeyoglu Mahmoud Abdelaziz Zahraa S. Elalfy |
| author_sort | Marwan A. ElBaset |
| collection | DOAJ |
| description | Hepatic fibrosis causes severe morbidity and death. No viable treatment can repair fibrosis and protect the liver until now. We intended to discover the empagliflozin’s (EMPA) hepatoprotective efficacy in thioacetamide (TAA)-induced hepatotoxicity by targeting AMPK/SIRT-1 activity and reducing HIF-1α. Rats were treated orally with EMPA (3 or 6 mg/kg) with TAA (100 mg/kg, IP) thrice weekly for 6 weeks. EMPA in both doses retracted the serum GGT, ALT, AST, ammonia, triglycerides, total cholesterol, and increased serum albumin. At the same time, EMPA (3 or 6 mg/kg) replenished the hepatic content of GSH, ATP, AMP, AMPK, or SIRT-1 and mitigated the hepatic content of MDA, TNF-α, IL-6, NF-κB, or HIF-1α in a dose-dependent manner. Likewise, hepatic photomicrograph stained with hematoxylin and eosin or Masson trichrome stain of EMPA (3 or 6 mg/kg) revealed marked regression of the hepatotoxic effect of TAA with minimal injury. Similarly, in rats given EMPA (3 or 6 mg/kg), the immunohistochemically of hepatic photomicrograph revealed minimal stain of either α-SMA or caspase-3 compared to the TAA group. Therefore, we concluded that EMPA possessed an antifibrotic effect by targeting AMPK/SIRT-1 activity and inhibiting HIF-1α. The present study provided new insight into a novel treatment of liver fibrosis. |
| first_indexed | 2024-03-09T19:18:57Z |
| format | Article |
| id | doaj.art-44d7519b69d34b0b9be33cd8d4b1aeae |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-09T19:18:57Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-44d7519b69d34b0b9be33cd8d4b1aeae2023-11-24T03:30:03ZengMDPI AGAntioxidants2076-39212022-10-011111215210.3390/antiox11112152Effect of Empagliflozin on Thioacetamide-Induced Liver Injury in Rats: Role of AMPK/SIRT-1/HIF-1α Pathway in Halting Liver FibrosisMarwan A. ElBaset0Rana S. Salem1Fairouz Ayman2Nadeen Ayman3Nooran Shaban4Sherif M. Afifi5Tuba Esatbeyoglu6Mahmoud Abdelaziz7Zahraa S. Elalfy8Pharmacology Department, Medical Research and Clinical Studies Institute, National Research Centre, 33 El-Bohouth St., Dokki, Cairo P.O. Box 12622, EgyptPharmacology and Toxicology Department, Faculty of Pharmacy, October University for Modern Science and Arts, Cairo 12451, EgyptPharmacology and Toxicology Department, Faculty of Pharmacy, October University for Modern Science and Arts, Cairo 12451, EgyptPharmacology and Toxicology Department, Faculty of Pharmacy, October University for Modern Science and Arts, Cairo 12451, EgyptPharmacology and Toxicology Department, Faculty of Pharmacy, October University for Modern Science and Arts, Cairo 12451, EgyptPharmacognosy Department, Faculty of Pharmacy, University of Sadat City, Sadat City 32897, EgyptDepartment of Food Development and Food Quality, Institute of Food Science and Human Nutrition, Gottfried Wilhelm Leibniz University Hannover, Am Kleinen Felde 30, 30167 Hannover, GermanyPharmacology and Toxicology Department, Faculty of Pharmacy, October University for Modern Science and Arts, Cairo 12451, EgyptPathology Department Medical Research and Clinical Studies Institute, National Research Centre, 33 El-Bohouth St., Dokki, Cairo P.O. Box 12622, EgyptHepatic fibrosis causes severe morbidity and death. No viable treatment can repair fibrosis and protect the liver until now. We intended to discover the empagliflozin’s (EMPA) hepatoprotective efficacy in thioacetamide (TAA)-induced hepatotoxicity by targeting AMPK/SIRT-1 activity and reducing HIF-1α. Rats were treated orally with EMPA (3 or 6 mg/kg) with TAA (100 mg/kg, IP) thrice weekly for 6 weeks. EMPA in both doses retracted the serum GGT, ALT, AST, ammonia, triglycerides, total cholesterol, and increased serum albumin. At the same time, EMPA (3 or 6 mg/kg) replenished the hepatic content of GSH, ATP, AMP, AMPK, or SIRT-1 and mitigated the hepatic content of MDA, TNF-α, IL-6, NF-κB, or HIF-1α in a dose-dependent manner. Likewise, hepatic photomicrograph stained with hematoxylin and eosin or Masson trichrome stain of EMPA (3 or 6 mg/kg) revealed marked regression of the hepatotoxic effect of TAA with minimal injury. Similarly, in rats given EMPA (3 or 6 mg/kg), the immunohistochemically of hepatic photomicrograph revealed minimal stain of either α-SMA or caspase-3 compared to the TAA group. Therefore, we concluded that EMPA possessed an antifibrotic effect by targeting AMPK/SIRT-1 activity and inhibiting HIF-1α. The present study provided new insight into a novel treatment of liver fibrosis.https://www.mdpi.com/2076-3921/11/11/2152antioxidantinflammationcytokineshepatic fibrosiscaspase-3 |
| spellingShingle | Marwan A. ElBaset Rana S. Salem Fairouz Ayman Nadeen Ayman Nooran Shaban Sherif M. Afifi Tuba Esatbeyoglu Mahmoud Abdelaziz Zahraa S. Elalfy Effect of Empagliflozin on Thioacetamide-Induced Liver Injury in Rats: Role of AMPK/SIRT-1/HIF-1α Pathway in Halting Liver Fibrosis Antioxidants antioxidant inflammation cytokines hepatic fibrosis caspase-3 |
| title | Effect of Empagliflozin on Thioacetamide-Induced Liver Injury in Rats: Role of AMPK/SIRT-1/HIF-1α Pathway in Halting Liver Fibrosis |
| title_full | Effect of Empagliflozin on Thioacetamide-Induced Liver Injury in Rats: Role of AMPK/SIRT-1/HIF-1α Pathway in Halting Liver Fibrosis |
| title_fullStr | Effect of Empagliflozin on Thioacetamide-Induced Liver Injury in Rats: Role of AMPK/SIRT-1/HIF-1α Pathway in Halting Liver Fibrosis |
| title_full_unstemmed | Effect of Empagliflozin on Thioacetamide-Induced Liver Injury in Rats: Role of AMPK/SIRT-1/HIF-1α Pathway in Halting Liver Fibrosis |
| title_short | Effect of Empagliflozin on Thioacetamide-Induced Liver Injury in Rats: Role of AMPK/SIRT-1/HIF-1α Pathway in Halting Liver Fibrosis |
| title_sort | effect of empagliflozin on thioacetamide induced liver injury in rats role of ampk sirt 1 hif 1α pathway in halting liver fibrosis |
| topic | antioxidant inflammation cytokines hepatic fibrosis caspase-3 |
| url | https://www.mdpi.com/2076-3921/11/11/2152 |
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