Refaie Marwa Monier Mahmoud, Majeed Nada Amgad Mohamed Abdel, Shehata Sayed, Muhammed Asmaa A, Hassan Salma M, Sherkawy Hoda S, Ali Fatma F, Saad Mohamed Rabie, Mohsen Mousa, Elsaghir Shereen Mohammed Mohammed, Fathy Enas, Beshay Olivia N
Department of Medical Pharmacology, Faculty of Medicine, Minia University, 61511, Minia, Egypt.
Department of Histology and Cell Biology, Faculty of Medicine, Minia University, 61511, Minia, Egypt.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Sep 15. doi: 10.1007/s00210-025-04581-2.
Intestinal ischemia reperfusion (II/R) is an abdominal critical case especially in neonates and during childhood affecting not only the intestinal tissue but also it could damage other remote organs including cardiac tissue even following surgical intervention. Immune homeostasis during II/R has a major role in controlling its progression. Thus, finding additive medical treatment besides the surgical one becomes an urgent need to keep the tissue. So that, we aimed to evaluate the possible ameliorative effect of diacerein (DIA) on II/R-induced injury in juvenile rats. Forty juvenile rats of Wistar albino species were randomly allocated into four different groups: sham group, DIA given group, II/R group via clamping superior mesenteric artery, DIA-treated group (50 mg/kg) with induction of II/R. Data of current model revealed a significant elevation of the measured cardiac enzymes, cleaved caspase-3, and nuclear factor kappa β (NF-κB) in the untreated ischemic group with disturbed oxidative stress parameters, accompanied with dysregulation of inflammasome/caspase-1/IL-1β and Wnt/β-catenin signaling cascades. Fortunately, upon co-administration of DIA, there is a significant decrease of cardiac enzymes, cleaved caspase-3, and NF-κB with normalization of oxidative stress parameters and regulation of inflammasome/caspase-1/IL-1β and Wnt/β-catenin pathways confirmed by marked mitigation of the histopathological changes. This effect of DIA is greatly attributed to its pharmacological properties including IL-1β antagonist effect, anti-oxidant, anti-apoptotic, and anti-inflammatory properties. Thus, DIA could be considered as an adjuvant future medical therapy for those cases of II/R.
肠缺血再灌注（II/R）是一种腹部危急病症，尤其在新生儿和儿童期，不仅会影响肠道组织，而且即使在手术干预后，也可能损害包括心脏组织在内的其他远处器官。II/R期间的免疫稳态在控制其进展中起主要作用。因此，除了手术治疗外，寻找辅助药物治疗成为维持组织的迫切需求。为此，我们旨在评估双醋瑞因（DIA）对幼年大鼠II/R诱导损伤的可能改善作用。将40只Wistar白化病幼年大鼠随机分为四组：假手术组、给予DIA组、通过夹闭肠系膜上动脉诱导II/R组、诱导II/R并给予DIA治疗组（50mg/kg）。当前模型的数据显示，在未经治疗的缺血组中，所测心肌酶、裂解的半胱天冬酶-3和核因子κB（NF-κB）显著升高，氧化应激参数紊乱，同时炎性小体/半胱天冬酶-1/白细胞介素-1β和Wnt/β-连环蛋白信号级联失调。幸运的是，在联合使用DIA后，心肌酶、裂解的半胱天冬酶-3和NF-κB显著降低，氧化应激参数恢复正常，炎性小体/半胱天冬酶-1/白细胞介素-1β和Wnt/β-连环蛋白途径得到调节，组织病理学变化明显减轻证实了这一点。DIA的这种作用很大程度上归因于其药理特性，包括白细胞介素-1β拮抗剂作用、抗氧化、抗凋亡和抗炎特性。因此，DIA可被视为未来II/R病例的辅助药物治疗。
