Protective Effects of Sitagliptin on Streptozotocin-Induced Hepatic Injury in Diabetic Rats: A Possible Mechanisms
Diabetes is a ubiquitous disease that causes several complications. It is associated with insulin resistance, which affects the metabolism of proteins, carbohydrates, and fats and triggers liver diseases such as fatty liver disease, steatohepatitis, fibrosis, and cirrhosis. Despite the effectiveness...
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MDPI AG
2023-12-01
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| author | Qamraa H. Alqahtani Samiyah Alshehri Ahlam M. Alhusaini Wedad S. Sarawi Sana S. Alqarni Raessa Mohamed Meha N. Kumar Juman Al-Saab Iman H. Hasan |
| author_facet | Qamraa H. Alqahtani Samiyah Alshehri Ahlam M. Alhusaini Wedad S. Sarawi Sana S. Alqarni Raessa Mohamed Meha N. Kumar Juman Al-Saab Iman H. Hasan |
| author_sort | Qamraa H. Alqahtani |
| collection | DOAJ |
| description | Diabetes is a ubiquitous disease that causes several complications. It is associated with insulin resistance, which affects the metabolism of proteins, carbohydrates, and fats and triggers liver diseases such as fatty liver disease, steatohepatitis, fibrosis, and cirrhosis. Despite the effectiveness of Sitagliptin (ST) as an antidiabetic drug, its role in diabetes-induced liver injury is yet to be fully investigated. Therefore, this study aims to investigate the effect of ST on hepatic oxidative injury, inflammation, apoptosis, and the mTOR/NF-κB/NLRP3 signaling pathway in streptozotocin (STZ)-induced liver injury. Rats were allocated into four groups: two nondiabetic groups, control rats and ST rats (100 mg/kg), and two diabetic groups induced by STZ, and they received either normal saline or ST for 90 days. Diabetic rats showed significant hyperglycemia, hyperlipidemia, and elevation in liver enzymes. After STZ induction, the results revealed remarkable increases in hepatic oxidative stress, inflammation, and hepatocyte degeneration. In addition, STZ upregulated the immunoreactivity of NF-κB/p65, NLRP3, and mTOR but downregulated IKB-α in liver tissue. The use of ST mitigated metabolic and hepatic changes induced by STZ; it also reduced oxidative stress, inflammation, and hepatocyte degeneration. The normal expression of NF-κB/p65, NLRP3, mTOR, and IKB-α were restored with ST treatment. Based on that, our study revealed for the first time the hepatoprotective effect of ST that is mediated by controlling inflammation, oxidative stress, and mTOR/NF-κB/NLRP3 signaling. |
| first_indexed | 2024-03-08T20:50:28Z |
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| language | English |
| last_indexed | 2024-03-08T20:50:28Z |
| publishDate | 2023-12-01 |
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| record_format | Article |
| series | Diseases |
| spelling | doaj.art-1f9919e79516440db79e90d2e033e6c62023-12-22T14:03:39ZengMDPI AGDiseases2079-97212023-12-0111418410.3390/diseases11040184Protective Effects of Sitagliptin on Streptozotocin-Induced Hepatic Injury in Diabetic Rats: A Possible MechanismsQamraa H. Alqahtani0Samiyah Alshehri1Ahlam M. Alhusaini2Wedad S. Sarawi3Sana S. Alqarni4Raessa Mohamed5Meha N. Kumar6Juman Al-Saab7Iman H. Hasan8Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 22452, Riyadh 11495, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 22452, Riyadh 11495, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 22452, Riyadh 11495, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 22452, Riyadh 11495, Saudi ArabiaDepartment of Clinical Laboratory Science, College of Applied Medical Sciences, King Saud University, P.O. Box 2925, Riyadh 11461, Saudi ArabiaDepartment of Histology, College of Medicine, King Saud University, P.O. Box 2925, Riyadh 11461, Saudi ArabiaDepartment of Clinical Medicine, Shanghai Medical College, Fudan University, Shanghai 200233, ChinaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 22452, Riyadh 11495, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 22452, Riyadh 11495, Saudi ArabiaDiabetes is a ubiquitous disease that causes several complications. It is associated with insulin resistance, which affects the metabolism of proteins, carbohydrates, and fats and triggers liver diseases such as fatty liver disease, steatohepatitis, fibrosis, and cirrhosis. Despite the effectiveness of Sitagliptin (ST) as an antidiabetic drug, its role in diabetes-induced liver injury is yet to be fully investigated. Therefore, this study aims to investigate the effect of ST on hepatic oxidative injury, inflammation, apoptosis, and the mTOR/NF-κB/NLRP3 signaling pathway in streptozotocin (STZ)-induced liver injury. Rats were allocated into four groups: two nondiabetic groups, control rats and ST rats (100 mg/kg), and two diabetic groups induced by STZ, and they received either normal saline or ST for 90 days. Diabetic rats showed significant hyperglycemia, hyperlipidemia, and elevation in liver enzymes. After STZ induction, the results revealed remarkable increases in hepatic oxidative stress, inflammation, and hepatocyte degeneration. In addition, STZ upregulated the immunoreactivity of NF-κB/p65, NLRP3, and mTOR but downregulated IKB-α in liver tissue. The use of ST mitigated metabolic and hepatic changes induced by STZ; it also reduced oxidative stress, inflammation, and hepatocyte degeneration. The normal expression of NF-κB/p65, NLRP3, mTOR, and IKB-α were restored with ST treatment. Based on that, our study revealed for the first time the hepatoprotective effect of ST that is mediated by controlling inflammation, oxidative stress, and mTOR/NF-κB/NLRP3 signaling.https://www.mdpi.com/2079-9721/11/4/184diabeticdipeptidyl peptidase-4 inhibitorsitagliptinSTZmTOR/NF-κB/NLRP3 signaling |
| spellingShingle | Qamraa H. Alqahtani Samiyah Alshehri Ahlam M. Alhusaini Wedad S. Sarawi Sana S. Alqarni Raessa Mohamed Meha N. Kumar Juman Al-Saab Iman H. Hasan Protective Effects of Sitagliptin on Streptozotocin-Induced Hepatic Injury in Diabetic Rats: A Possible Mechanisms Diseases diabetic dipeptidyl peptidase-4 inhibitor sitagliptin STZ mTOR/NF-κB/NLRP3 signaling |
| title | Protective Effects of Sitagliptin on Streptozotocin-Induced Hepatic Injury in Diabetic Rats: A Possible Mechanisms |
| title_full | Protective Effects of Sitagliptin on Streptozotocin-Induced Hepatic Injury in Diabetic Rats: A Possible Mechanisms |
| title_fullStr | Protective Effects of Sitagliptin on Streptozotocin-Induced Hepatic Injury in Diabetic Rats: A Possible Mechanisms |
| title_full_unstemmed | Protective Effects of Sitagliptin on Streptozotocin-Induced Hepatic Injury in Diabetic Rats: A Possible Mechanisms |
| title_short | Protective Effects of Sitagliptin on Streptozotocin-Induced Hepatic Injury in Diabetic Rats: A Possible Mechanisms |
| title_sort | protective effects of sitagliptin on streptozotocin induced hepatic injury in diabetic rats a possible mechanisms |
| topic | diabetic dipeptidyl peptidase-4 inhibitor sitagliptin STZ mTOR/NF-κB/NLRP3 signaling |
| url | https://www.mdpi.com/2079-9721/11/4/184 |
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