Dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin ameliorates inflammation and autophagy in mice hindlimb ischemia–reperfusion injury
Abstract Background Ischemia-reperfusion injury (I/R) for skeletal muscle usually results from vascular injuries or trauma. Sitagliptin (STG) is an effective member of the dipeptidyl peptidase-4 (DPP-4) inhibitors drug family that plays roles in oxidative stress regulation, inflammation, and autopha...
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| Format: | Article |
| Language: | English |
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SpringerOpen
2024-12-01
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| Series: | Beni-Suef University Journal of Basic and Applied Sciences |
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| Online Access: | https://doi.org/10.1186/s43088-024-00558-x |
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| author | Marwa Abdeltawab Mohammed Dalia Abdel-Wahab Mohamed Asmaa A. Abo Zeid Marian F. L. Abdelmalak Maha Tarek Mohamed Dina Sayed Abdelrahim |
| author_facet | Marwa Abdeltawab Mohammed Dalia Abdel-Wahab Mohamed Asmaa A. Abo Zeid Marian F. L. Abdelmalak Maha Tarek Mohamed Dina Sayed Abdelrahim |
| author_sort | Marwa Abdeltawab Mohammed |
| collection | DOAJ |
| description | Abstract Background Ischemia-reperfusion injury (I/R) for skeletal muscle usually results from vascular injuries or trauma. Sitagliptin (STG) is an effective member of the dipeptidyl peptidase-4 (DPP-4) inhibitors drug family that plays roles in oxidative stress regulation, inflammation, and autophagy control. In this study, we evaluated the protective roles of STG against I/R of gastrocnemius muscle and the underlying mechanisms. Materials and methods Forty-eight mice were randomly allocated into three groups: Group I (n = 24): control group which was subdivided equally into subgroup IA; negative control, subgroup IB; sitagliptin (STG), Group II (n = 12): ischemia–reperfusion injury (I/R), and Group III (n = 12): sitagliptin pretreatment (300 mg/kg/ day; p.o.) for two weeks followed by ischemia–reperfusion injury (STG + I/R). We measured SOD activity and MDA level to assess oxidative stress. Moreover, GLP-1/p-PI3K/ p-AKT expression levels were investigated. Autophagy was estimated by assessing lncRNA H19, Beclin-1 and ATG7 expression by RT-qPCR analysis. Inflammatory markers were assessed by iNOS and NF‐κB expression using immunohistochemistry. Results Our results revealed that STG pretreatment significantly attenuated oxidative stress and inflammation and upregulated GLP-1, p-PI3K, and p-AKT protein levels. Also, LnRNA H19, Becline-1, and ATG7 mRNA expression were downregulated as well as decrease the expression of the inflammatory markers iNOS and NF‐κB with STG pretreatment. Conclusion Our results highlighted the useful effects of Sitagliptin during hind limb I/R that could be mediated by antioxidant, anti-inflammatory effects, and attenuation of excessive autophagy. |
| format | Article |
| id | doaj-art-b312f07ffe9241d79dfebe02c4e5f4e9 |
| institution | Kabale University |
| issn | 2314-8543 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Beni-Suef University Journal of Basic and Applied Sciences |
| spelling | doaj-art-b312f07ffe9241d79dfebe02c4e5f4e92024-12-08T12:40:55ZengSpringerOpenBeni-Suef University Journal of Basic and Applied Sciences2314-85432024-12-0113111410.1186/s43088-024-00558-xDipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin ameliorates inflammation and autophagy in mice hindlimb ischemia–reperfusion injuryMarwa Abdeltawab Mohammed0Dalia Abdel-Wahab Mohamed1Asmaa A. Abo Zeid2Marian F. L. Abdelmalak3Maha Tarek Mohamed4Dina Sayed Abdelrahim5Physiology Department, Faculty of Medicine, Beni-Suef UniversityMedical Biochemistry and Molecular Biology Department, Faculty of Medicine, Ain Shams UniversityHistology and Cell Biology Department, Faculty of Medicine, Ain Shams UniversityPharmacology Department, Faculty of Medicine, Ain Shams UniversityPharmacology Department, Faculty of Medicine, Ain Shams UniversityPharmacology Department, Faculty of Medicine, Ain Shams UniversityAbstract Background Ischemia-reperfusion injury (I/R) for skeletal muscle usually results from vascular injuries or trauma. Sitagliptin (STG) is an effective member of the dipeptidyl peptidase-4 (DPP-4) inhibitors drug family that plays roles in oxidative stress regulation, inflammation, and autophagy control. In this study, we evaluated the protective roles of STG against I/R of gastrocnemius muscle and the underlying mechanisms. Materials and methods Forty-eight mice were randomly allocated into three groups: Group I (n = 24): control group which was subdivided equally into subgroup IA; negative control, subgroup IB; sitagliptin (STG), Group II (n = 12): ischemia–reperfusion injury (I/R), and Group III (n = 12): sitagliptin pretreatment (300 mg/kg/ day; p.o.) for two weeks followed by ischemia–reperfusion injury (STG + I/R). We measured SOD activity and MDA level to assess oxidative stress. Moreover, GLP-1/p-PI3K/ p-AKT expression levels were investigated. Autophagy was estimated by assessing lncRNA H19, Beclin-1 and ATG7 expression by RT-qPCR analysis. Inflammatory markers were assessed by iNOS and NF‐κB expression using immunohistochemistry. Results Our results revealed that STG pretreatment significantly attenuated oxidative stress and inflammation and upregulated GLP-1, p-PI3K, and p-AKT protein levels. Also, LnRNA H19, Becline-1, and ATG7 mRNA expression were downregulated as well as decrease the expression of the inflammatory markers iNOS and NF‐κB with STG pretreatment. Conclusion Our results highlighted the useful effects of Sitagliptin during hind limb I/R that could be mediated by antioxidant, anti-inflammatory effects, and attenuation of excessive autophagy.https://doi.org/10.1186/s43088-024-00558-xIschemia–reperfusion injuryLnRNAH19AutophagySitagliptinATG7 |
| spellingShingle | Marwa Abdeltawab Mohammed Dalia Abdel-Wahab Mohamed Asmaa A. Abo Zeid Marian F. L. Abdelmalak Maha Tarek Mohamed Dina Sayed Abdelrahim Dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin ameliorates inflammation and autophagy in mice hindlimb ischemia–reperfusion injury Beni-Suef University Journal of Basic and Applied Sciences Ischemia–reperfusion injury LnRNAH19 Autophagy Sitagliptin ATG7 |
| title | Dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin ameliorates inflammation and autophagy in mice hindlimb ischemia–reperfusion injury |
| title_full | Dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin ameliorates inflammation and autophagy in mice hindlimb ischemia–reperfusion injury |
| title_fullStr | Dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin ameliorates inflammation and autophagy in mice hindlimb ischemia–reperfusion injury |
| title_full_unstemmed | Dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin ameliorates inflammation and autophagy in mice hindlimb ischemia–reperfusion injury |
| title_short | Dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin ameliorates inflammation and autophagy in mice hindlimb ischemia–reperfusion injury |
| title_sort | dipeptidyl peptidase 4 dpp 4 inhibitor sitagliptin ameliorates inflammation and autophagy in mice hindlimb ischemia reperfusion injury |
| topic | Ischemia–reperfusion injury LnRNAH19 Autophagy Sitagliptin ATG7 |
| url | https://doi.org/10.1186/s43088-024-00558-x |
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