Althobaiti Fayez, Taher Ehab S, Ahmed Alkeridis Lamya, Ibrahim Ateya M, El-Shafai Nagi, A Al-Shuraym Laila, Fericean Liana, Imbrea Florin, A Kassab Mohamed, Farrag Foad A, Abdeen Ahmed, Almalki Daklallah A, Al-Farga Ammar, Afifi Mohamed, Shukry Mustafa
Department of Biotechnology, College of Science, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
Department of Basic Medical and Dental Sciences, Faculty of Dentistry, Zarqa University, Zarqa 13110, Jordan.
ACS Omega. 2024 May 21;9(22):23949-23962. doi: 10.1021/acsomega.4c02285. eCollection 2024 Jun 4.
has been the subject of plentiful studies due to its purported health advantages; nevertheless, additional investigation is required to determine whether several chronic diseases may be treated or avoided with its nanoform. Therefore, we set out to examine nanoparticles (SNPs) to protect against kidney impairment caused by Streptozotocin (STZ) in diabetic rats, precisely focusing on its effect and the cellular intracellular pathways involved. Male Wistar rats were assigned into four groups: Group 1 was set as control, comprising the normal rats; group 2 was administered SNPs (0.5 mg/kg BW, once/day) orally for 84 consecutive days; group 3, STZ-diabetic rats were injected with STZ (65 mg/kg BW); and group 4, in which the diabetic rats were treated with SNPs. After inducing diabetes in rats for 84 days, the animals were euthanized. The results disclosed that SNP treatment substantially ( < 0.05) improved the glucose and glycated hemoglobin levels (HbA1c %), insulin, C-peptide, and cystatin C deterioration in diabetic rats. Furthermore, SNP administration significantly lowered ( < 0.05) nitric oxide (NO) and malondialdehyde (MDA) levels in renal tissue and enhanced kidney function metrics, as well as improved the antioxidant capacity of the renal tissue. In addition, oral SNPs overcame the diabetic complications concerning diabetic nephropathy, indicated by downregulation and upregulation of apoptotic and antiapoptotic genes, respectively, along with prominent modulation of the antiangiogenic marker countenance level, improving kidney function. SNP modulated the nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 (NRF2/HO-1) pathways and inhibited the nuclear factor-κB (NF-κB) expression, strengthening the SNP pathways in alleviating diabetic nephropathy. The histopathology results corroborated the obtained biochemical and molecular observations, suggesting the therapeutic potential of SNPs in diabetic nephropathy via mechanisms other than its significant antioxidant and hypoglycemic effects, including modulation of antiangiogenic and inflammatory mediators and the NRF2/HO-1 pathways.
由于其所谓的健康益处，它一直是大量研究的主题；然而，需要进一步研究以确定其纳米形式是否可以治疗或预防几种慢性疾病。因此，我们着手研究纳米颗粒（SNPs）对糖尿病大鼠中链脲佐菌素（STZ）引起的肾脏损伤的保护作用，具体关注其作用及相关的细胞内信号通路。雄性Wistar大鼠被分为四组：第1组设为对照组，由正常大鼠组成；第2组连续84天每天口服SNPs（0.5mg/kg体重）；第3组，给STZ诱导的糖尿病大鼠注射STZ（65mg/kg体重）；第4组，用SNPs治疗糖尿病大鼠。在大鼠诱导糖尿病84天后，将动物安乐死。结果显示，SNPs治疗显著（P<0.05）改善了糖尿病大鼠的血糖、糖化血红蛋白水平（HbA1c%）、胰岛素、C肽和胱抑素C的恶化情况。此外，给予SNPs显著降低（P<0.05）了肾组织中一氧化氮（NO）和丙二醛（MDA）水平，增强了肾功能指标，并提高了肾组织的抗氧化能力。此外，口服SNPs克服了与糖尿病肾病相关的糖尿病并发症，分别通过凋亡和抗凋亡基因的下调和上调以及抗血管生成标志物面容水平的显著调节来表明，改善了肾功能。SNPs调节了核因子红细胞2相关因子2和血红素加氧酶-1（NRF2/HO-1）信号通路，并抑制了核因子-κB（NF-κB）的表达，加强了SNPs在减轻糖尿病肾病中的信号通路。组织病理学结果证实了所获得的生化和分子观察结果，表明SNPs在糖尿病肾病中的治疗潜力，其机制除了显著的抗氧化和降血糖作用外，还包括调节抗血管生成和炎症介质以及NRF2/HO-1信号通路。
