Elbadr Mohamed M, Galal Heba A, Hetta Helal F, Elfadil Hassabelrasoul, Alanazi Fawaz E, Fawzy Shereen, Aljohani Hashim M, Abd Ellah Noura H, Ali Marwa F, Dyab Ahmed K, Ahmed Esraa A
Department of Medical Pharmacology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt.
Department of Pharmacology, Faculty of Veterinary Medicine, Assiut University, Assiut 71515, Egypt.
Diseases. 2025 Mar 19;13(3):87. doi: 10.3390/diseases13030087.
Chronic inflammation and immune dysregulation are key drivers of diabetes complications. Rivaroxaban (RX) and sitagliptin (SITA) are established therapies for thromboembolism and glycemic control, respectively. This study evaluated the novel therapeutic potential of nano-rivaroxaban (NRX) alone and in combination with sitagliptin (SITA) in mitigating inflammation and restoring immune balance in streptozotocin (STZ)-induced diabetic rats.
Type 2 diabetes was induced in rats using a single injection of STZ (60 mg/kg). Animals were divided into five groups: control, STZ-diabetic, RX-treated (5 mg/kg), NRX-treated (5 mg/kg), and NRX+SITA-treated (5 mg/kg + 10 mg/kg). After 4 weeks of treatment, blood glucose, coagulation markers, pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), and anti-inflammatory cytokines (IL-35, TGF-β1, IL-10) were analyzed. Histopathological examination of the liver, kidney, pancreas, and spleen was conducted. Immunohistochemistry was used to assess hepatic NF-κB expression.
STZ significantly elevated pro-inflammatory cytokines (IL-1β, TNF-α, IL-6) and anti-inflammatory cytokines (IL-35, TGF-β1, IL-10), along with increased hepatic NF-κB expression and histopathological abnormalities in immune organs. NRX significantly reduced inflammatory cytokines, improved histopathological changes in organs, and decreased hepatic NF-κB expression. The combination therapy (NRX + SITA) achieved superior immune modulation, with enhanced cytokine profile restoration, reduced hepatic NF-κB expression, and near-complete histopathological normalization.
This study underscores the promise of combining nanoparticle-based drug delivery with established therapies like sitagliptin to achieve superior immune modulation and inflammation control, presenting a potential therapeutic strategy for managing diabetes complications.
慢性炎症和免疫失调是糖尿病并发症的关键驱动因素。利伐沙班（RX）和西他列汀（SITA）分别是用于治疗血栓栓塞和控制血糖的既定疗法。本研究评估了纳米利伐沙班（NRX）单独使用以及与西他列汀（SITA）联合使用在减轻链脲佐菌素（STZ）诱导的糖尿病大鼠炎症和恢复免疫平衡方面的新型治疗潜力。
通过单次注射STZ（60mg/kg）诱导大鼠患2型糖尿病。动物分为五组：对照组、STZ糖尿病组、RX治疗组（5mg/kg）、NRX治疗组（5mg/kg）和NRX+SITA治疗组（5mg/kg+10mg/kg）。治疗4周后，分析血糖、凝血指标、促炎细胞因子（TNF-α、IL-1β、IL-6）和抗炎细胞因子（IL-35、TGF-β1、IL-10）。对肝脏、肾脏、胰腺和脾脏进行组织病理学检查。采用免疫组织化学法评估肝脏NF-κB表达。
STZ显著升高促炎细胞因子（IL-1β、TNF-α、IL-6）和抗炎细胞因子（IL-35、TGF-β1、IL-10），同时肝脏NF-κB表达增加，免疫器官出现组织病理学异常。NRX显著降低炎症细胞因子，改善器官组织病理学变化，并降低肝脏NF-κB表达。联合治疗（NRX+SITA）实现了更好的免疫调节，增强了细胞因子谱恢复，降低了肝脏NF-κB表达，组织病理学几乎完全恢复正常。
本研究强调了将基于纳米颗粒的药物递送与西他列汀等既定疗法相结合以实现更好的免疫调节和炎症控制的前景，为管理糖尿病并发症提供了一种潜在的治疗策略。
