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冻干水果提取物通过调节庆大霉素诱导的肾毒性小鼠模型中的诱变和氧化应激,减轻急性氧化还原稳态失衡。

-Lyophilized Fruit Extract Attenuated Acute Redox-Homeostatic Imbalance via Mutagenic and Oxidative Stress Modulation in Mice Model on Gentamicin-Induced Nephrotoxicity.

作者信息

Petkova-Parlapanska Kamelia, Stefanov Ivaylo, Ananiev Julian, Georgiev Tsvetelin, Hadzhibozheva Petya, Petrova-Tacheva Veselina, Kaloyanov Nikolay, Georgieva Ekaterina, Nikolova Galina, Karamalakova Yanka

机构信息

Department of Chemistry and Biochemistry, Medical Faculty, Trakia University, 11 Armeiska Str., 6000 Stara Zagora, Bulgaria.

Department of General and Clinical Pathology, Forensic Medicine and Deontology, Faculty of Medicine, Trakia University, 11 Armeiska Str., 6000 Stara Zagora, Bulgaria.

出版信息

Pharmaceuticals (Basel). 2025 Jan 13;18(1):85. doi: 10.3390/ph18010085.

Abstract

Gentamicin (GM) administration is associated with decreased metabolism, increased oxidative stress, and induction of nephrotoxicity. L., containing flavonoids, anthocyanins, and phytosterols, possesses antioxidant and anti-inflammatory potential. The present study aimed to investigate the nephroprotective and anti-inflammatory potential of lyophilized fruit extract () to reduce acute oxidative stress and residual toxicity of GM in a 7-day experimental model in Balb/c rodents. The extract was lyophilized (300 rpm; 10 min; -45 °C) to improve pharmacological properties. Balb/c mice were divided into four (n = 6) groups: controls; extract per os (120 mg kg day bw); GM (200 mg kg day bw) (4); and GM + therapy. The activities of antioxidant and renal enzymes, cytokines, and levels of oxidative stress biomarkers-Hydroxiproline, CysC, GST, KIM-1, PGC-1α, MDA, GSPx-were analyzed by ELISA tests. The ROS and RNS levels, as well as 5-MSL-protein oxidation, were measured by EPR spectroscopy. The antioxidant-protective effect of extract (120 mg kg) was demonstrated by reduced MDA, ROS, and RNS and increased activation of endogenous enzymes. Furthermore, extract significantly reduced the expression of IL-1β, IL-6, IL-10, TNF-α, IFN-γ, and KIM-1 and regulated collagen/protein (PGC-1α and albumin) deposition in renal tissues. Histological evaluation confirmed that (120 mg kg) attenuated renal dysfunction and structural damage by modulating oxidative stress and acute inflammation and could be used as an anti-fibrotic alternative in GM nephrotoxicity.

摘要

庆大霉素(GM)的使用与代谢降低、氧化应激增加以及肾毒性的诱导有关。L.含有黄酮类化合物、花青素和植物甾醇,具有抗氧化和抗炎潜力。本研究旨在探讨冻干水果提取物()在Balb/c啮齿动物的7天实验模型中减轻GM急性氧化应激和残留毒性的肾保护和抗炎潜力。将提取物冻干(300转/分钟;10分钟;-45°C)以改善药理特性。将Balb/c小鼠分为四组(n = 6):对照组;口服提取物(120毫克/千克体重/天);GM(200毫克/千克体重/天)(4);以及GM + 治疗组。通过ELISA试验分析抗氧化和肾酶、细胞因子的活性以及氧化应激生物标志物——羟脯氨酸、胱抑素C、谷胱甘肽S-转移酶、肾损伤分子-1、过氧化物酶体增殖物激活受体γ共激活因子-1α、丙二醛、谷胱甘肽过氧化物酶的水平。通过电子顺磁共振光谱法测量活性氧和活性氮水平以及5-MSL-蛋白质氧化。提取物(120毫克/千克)的抗氧化保护作用通过降低丙二醛、活性氧和活性氮以及增加内源性酶的激活来证明。此外,提取物显著降低白细胞介素-1β、白细胞介素-6、白细胞介素-10、肿瘤坏死因子-α、干扰素-γ和肾损伤分子-1的表达,并调节肾组织中胶原蛋白/蛋白质(过氧化物酶体增殖物激活受体γ共激活因子-1α和白蛋白)的沉积。组织学评估证实,(120毫克/千克)通过调节氧化应激和急性炎症减轻了肾功能障碍和结构损伤,可作为GM肾毒性的抗纤维化替代物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f464/11768164/5e11eadd2eb6/pharmaceuticals-18-00085-sch001.jpg

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