Sabra Mahmoud S, Allam Essmat A H, El-Aal Mohamed Abd, Hassan Nessma H, Mostafa Al-Hassan Mohammed, Ahmed Ahmed A N
Pharmacology Department, Faculty of Veterinary Medicine, Assiut University, Assiut, 71526, Egypt.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Assiut University, Assiut, 71526, Egypt.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Jan;398(1):933-950. doi: 10.1007/s00210-024-03303-4. Epub 2024 Aug 2.
In acute renal failure (ARF), the glomerular filtration rate is reduced, and nitrogenous waste products accumulate persistently, which can last anywhere from a few hours to several days. There is hope for a reversal of the rapid loss of renal function caused by this condition. This study, with gentamicin-induced acute ARF as a prospective setting, sets out to examine the reno-protective benefits of virgin coconut oil (VCO) and GSH. Furthermore, the study evaluated the effect of medication nanoparticle compositions on several kidney function markers. The induction of ARF is achieved with the intraperitoneal injection of gentamicin. To assess renal function, rats underwent 24 h of dehydration and hunger before their deaths. The study examined various aspects, including kidney function tests, markers of oxidative stress, histology of kidney tissue, inflammatory cytokines, immunohistochemistry expression of nuclear factor-kappa B (NF-κB), and specific biomarkers for kidney tissue damage, such as kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL). The results of our study indicated that the combination of VCO and GSH, using both regular and nanoparticle formulations, had a better protective impact on the kidneys compared to using either drug alone. The recovery of renal tissue and serum markers, which are symptomatic of organ damage, indicates improvement. This was also demonstrated by the reduction in tubular expression of TNF-α, IL-1β, KIM-1, and NGAL. The immunohistochemical studies showed that the combination therapy, especially with the nanoforms, greatly improved the damaged cellular changes in the kidneys, as shown by higher levels of NF-κB. The study shows that VCO and GSH, when administered individually or combined, significantly improve ARF in a gentamicin-induced rat model, highlighting potential therapeutic implications. Notably, the combined nanoparticulate formulations exhibit substantial effectiveness.
在急性肾衰竭（ARF）中，肾小球滤过率降低，含氮废物持续积累，这种情况可持续数小时至数天。由这种病症导致的肾功能快速丧失有望得到逆转。本研究以前瞻性的庆大霉素诱导急性ARF为背景，着手研究初榨椰子油（VCO）和谷胱甘肽（GSH）的肾脏保护益处。此外，该研究评估了药物纳米颗粒组合物对几种肾功能标志物的影响。通过腹腔注射庆大霉素来诱导ARF。为评估肾功能，大鼠在处死前经历24小时脱水和饥饿。该研究考察了多个方面，包括肾功能测试、氧化应激标志物、肾组织组织学、炎性细胞因子、核因子-κB（NF-κB）的免疫组化表达以及肾组织损伤的特异性生物标志物，如肾损伤分子-1（KIM-1）和中性粒细胞明胶酶相关脂质运载蛋白（NGAL）。我们的研究结果表明，与单独使用任何一种药物相比，使用常规和纳米颗粒制剂的VCO和GSH组合对肾脏具有更好的保护作用。肾组织和血清标志物的恢复是器官损伤的症状表现，这表明情况有所改善。TNF-α、IL-1β、KIM-1和NGAL肾小管表达的降低也证明了这一点。免疫组化研究表明，联合治疗，尤其是纳米形式的联合治疗，极大地改善了肾脏受损的细胞变化，NF-κB水平升高即表明了这一点。该研究表明，单独或联合使用VCO和GSH可显著改善庆大霉素诱导的大鼠模型中的ARF，突出了潜在的治疗意义。值得注意的是，联合纳米颗粒制剂显示出显著的有效性。
