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Interleukin 1β receptor blocker (Anakinra) and regenerative stem cell therapy: two novel approaches effectively ameliorating diabetic cardiomyopathy.
- Source :
-
Naunyn-Schmiedeberg's archives of pharmacology [Naunyn Schmiedebergs Arch Pharmacol] 2024 Oct; Vol. 397 (10), pp. 8023-8041. Date of Electronic Publication: 2024 May 22. - Publication Year :
- 2024
-
Abstract
- Diabetic cardiomyopathy (DCM) is a serious common complication of diabetes. Unfortunately, there is no satisfied treatment for those patients and more studies are in critical need to cure them. Therefore, we aimed to carry out our current research to explore the role of two novel therapeutic approaches: one a biological drug aimed to block inflammatory signaling of the IL 1beta (IL1β) axis, namely, anakinra; the other is provision of anti-inflammatory regenerative stem cells. Wistar male rats were allocated into four groups: control group: type 2 diabetes mellitus (DM) induced by 6-week high-fat diet (HFD) followed by a single-dose streptozotocin (STZ) 35 mg/kg i.p., then rats were allocated into: DM: untreated; DM BM-MSCs: received a single dose of BM-MSCs (1 × 10 <superscript>6</superscript> cell/rat) into rat tail vein; DM-Anak received Anak 0.5 μg/kg/day i.p. for 2 weeks. Both therapeutic approaches improved cardiac performance, fibrosis, and hypertrophy. In addition, blood glucose and insulin resistance decreased, while the antioxidant parameter, nuclear factor erythroid 2-related factor 2 (Nrf2) and interleukin 10 (IL10), and anti-inflammatory agent increased. Furthermore, there is a significant reduction in tumor necrosis factor alpha (TNFα), IL1β, caspase1, macrophage marker CD 11b, inducible nitric oxide synthase (iNOS), and T-cell marker CD 8. Both Anak and BM-MSCs effectively ameliorated inflammatory markers and cardiac performance as compared to non-treated diabetics. Improvement is mostly due to anti-inflammatory, antioxidant, anti-apoptotic properties, and regulation of TNFα/IL1β/caspase1 and Nrf2/IL10 pathways.<br /> (© 2024. The Author(s).)
- Subjects :
- Animals
Male
Rats
Mesenchymal Stem Cell Transplantation methods
Diet, High-Fat
Interleukin-1beta metabolism
Diabetes Mellitus, Type 2 drug therapy
Diabetes Mellitus, Type 2 therapy
Blood Glucose drug effects
Blood Glucose metabolism
Diabetic Cardiomyopathies drug therapy
Rats, Wistar
Diabetes Mellitus, Experimental drug therapy
Diabetes Mellitus, Experimental therapy
Interleukin 1 Receptor Antagonist Protein pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1432-1912
- Volume :
- 397
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Naunyn-Schmiedeberg's archives of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 38775851
- Full Text :
- https://doi.org/10.1007/s00210-024-03152-1