Ramadan Hanaa, Moustafa Nadia, Ahmed Rasha Rashad, El-Shahawy Ahmed A G, Eldin Zienab E, Al-Jameel Suhailah S, Amin Kamal Adel, Ahmed Osama M, Abdul-Hamid Manal
Cell Biology, Histology and Genetics Division, Department of Zoology, Faculty of Science, Beni-Suef University, P.O. Box 62521, Beni-Suef, Egypt.
Materials Science and Nanotechnology Department, Faculty of Postgraduate Studies for Advanced Sciences (PSAS), Beni-Suef University, 62521 Beni-Suef 12827, Egypt.
Heliyon. 2024 Aug 6;10(15):e35636. doi: 10.1016/j.heliyon.2024.e35636. eCollection 2024 Aug 15.
The current study inspects the therapeutic effects of orally ingested insulin-loaded chitosan nanobeads (INS-CsNBs) with a pectin-dextrin (PD) coating on streptozotocin (STZ)-induced diabetes in Wistar rats. The study also assessed antioxidant effects in pancreatic tissue homogenate, insulin, C-peptide, and inflammatory markers interleukin-1 beta and interleukin-6 (IL-1β and IL-6) in serum. Additionally, histopathological and immunohistochemical examination of insulin granules, oxidative stress, nuclear factor kappa B (NF-κB P65), and sirtuin-1 (SIRT-1) protein detection, as well as gene expression of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), B-cell lymphoma 2 (Bcl2), and Bcl-2-associated X protein (Bax) in pancreatic tissue were investigated. After induction of diabetes with STZ, rats were allocated into 6 groups: the normal control (C), the diabetic control (D), and the diabetic groups treated with INS-CsNBs coated with PD shell (50 IU/kg) (NF), free oral insulin (10 IU/kg) (FO), CsNBs-PD shell (50 IU/kg) (NB), and subcutaneous insulin (10 IU/kg) (Sc). The rats were treated daily for four weeks. Treatment of diabetic rats with INS-CsNBs coated with PD shell resulted in a significant improvement in blood glucose levels, elevated antioxidant activities, decreased NF-κB P65, IL-1β, and IL-6 levels, upregulated Nrf-2 and HO-1, in addition to a marked improvement in the histological architecture and integrity compared to the diabetic group. The effects of oral INS-CsNBs administration were comparable to those of subcutaneous insulin. In conclusion, oral administration of INS-loaded Cs-NBs with a pectin-dextrin shell demonstrated an ameliorative effect on STZ-induced diabetes, avoiding the drawbacks of subcutaneous insulin.
本研究考察了口服负载胰岛素的壳聚糖纳米珠(INS-CsNBs)及其果胶-糊精(PD)包衣对链脲佐菌素(STZ)诱导的Wistar大鼠糖尿病的治疗效果。该研究还评估了胰腺组织匀浆中的抗氧化作用、血清中的胰岛素、C肽以及炎症标志物白细胞介素-1β和白细胞介素-6(IL-1β和IL-6)。此外,还进行了胰岛素颗粒的组织病理学和免疫组织化学检查、氧化应激、核因子κB(NF-κB P65)和沉默调节蛋白-1(SIRT-1)蛋白检测,以及胰腺组织中核因子红细胞2相关因子2(Nrf2)、血红素加氧酶-1(HO-1)、B细胞淋巴瘤2(Bcl2)和Bcl-2相关X蛋白(Bax)的基因表达研究。用STZ诱导糖尿病后,将大鼠分为6组:正常对照组(C)、糖尿病对照组(D)以及用PD壳包衣的INS-CsNBs(50 IU/kg)治疗的糖尿病组(NF)、游离口服胰岛素(10 IU/kg)(FO)、CsNBs-PD壳(50 IU/kg)(NB)和皮下胰岛素(10 IU/kg)(Sc)。大鼠每日接受治疗,持续四周。用PD壳包衣的INS-CsNBs治疗糖尿病大鼠可显著改善血糖水平,提高抗氧化活性,降低NF-κB P65、IL-1β和IL-6水平,上调Nrf-2和HO-1,与糖尿病组相比,组织学结构和完整性也有明显改善。口服INS-CsNBs的效果与皮下注射胰岛素相当。总之,口服负载胰岛素的果胶-糊精壳Cs-NBs对STZ诱导的糖尿病具有改善作用,避免了皮下注射胰岛素的缺点。