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Interleukin 1β receptor blocker (Anakinra) and regenerative stem cell therapy: two novel approaches effectively ameliorating diabetic cardiomyopathy.

Authors :
Mahmoud LM
Mageed AAAA
Saadallah JM
Youssef MF
Rashed LA
Ammar HI
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).)

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