关键词: ARF GSH Gentamicin KIM-1 NGAL Nanoparticles

来  源:   DOI:10.1007/s00210-024-03303-4

Abstract:
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.
摘要:
在急性肾衰竭(ARF)中,肾小球滤过率降低,含氮废物持续积累,可以持续几个小时到几天。有希望逆转由这种情况引起的肾功能的快速丧失。这项研究,以庆大霉素诱导的急性ARF为前瞻性背景,着手研究初榨椰子油(VCO)和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。通过腹膜内注射庆大霉素实现ARF的诱导。为了评估肾功能,老鼠在死前经历了24小时的脱水和饥饿。这项研究检查了各个方面,包括肾功能测试,氧化应激的标志物,肾组织的组织学,炎性细胞因子,核因子-κB(NF-κB)的免疫组化表达,和肾组织损伤的特定生物标志物,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,VCO和GSH的组合,使用常规和纳米颗粒配方,与单独使用这两种药物相比,对肾脏有更好的保护作用。肾组织和血清标志物的恢复,这是器官损伤的症状,表明改进。TNF-α的肾小管表达减少也证明了这一点。IL-1β,KIM-1和NGAL.免疫组织化学研究表明,联合治疗,尤其是纳米形式,大大改善了肾脏受损的细胞变化,如较高水平的NF-κB所示。研究表明,VCO和GSH,当单独或联合给药时,在庆大霉素诱导的大鼠模型中显著改善ARF,强调潜在的治疗意义。值得注意的是,组合的纳米颗粒制剂表现出实质性的有效性。
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