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

Autor: Mahmoud LM; Department of Physiology, Faculty of Medicine, Cairo University, Giza, Egypt., Mageed AAAA; Department of Physiology, Faculty of Medicine, Cairo University, Giza, Egypt. aya.abdelmageed@kasralainy.edu.eg., Saadallah JM; Department of Physiology, Faculty of Medicine, Cairo University, Giza, Egypt., Youssef MF; Department of Histology, Faculty of Medicine, Cairo University, Giza, Egypt., Rashed LA; Department of Biochemistry, Faculty of Medicine, Cairo University, Giza, Egypt., Ammar HI; Department of Physiology, Faculty of Medicine, Cairo University, Giza, Egypt.
Jazyk: angličtina
Zdroj: 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.
DOI: 10.1007/s00210-024-03152-1
Abstrakt: 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 6 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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