Investigation the effects of 2-aminoethoxydiphenyl borate (2-APB) on aminoglycoside nephrotoxicity.

IF 1.1 4区 医学 Q4 MICROSCOPY Ultrastructural Pathology Pub Date : 2024-01-02 Epub Date: 2024-01-09 DOI:10.1080/01913123.2023.2278629
Özge Kendirlinan, Yurdun Kuyucu, Bilge Güzelel, Ebru Dündar Yenilmez, Abdullah Tuli, Gülşah Seydaoğlu, Ufuk Özgü Mete
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Abstract

Investigation the protective effect of transient receptor potential channel modulator 2-Aminoethoxydiphenyl Borate (2-APB) on aminoglycoside nephrotoxicity caused by reactive oxygen species, calcium-induced apoptosis and inflammation was aimed. Forty Wistar rats were divided (n=8) as follows: Control group; DMSO group; 2-APB group; Gentamicin group (injected 100 mg/kg gentamicin intramuscularly for 10 days); Gentamicin+ 2-APB group (injected 2 mg/kg 2-APB intraperitoneally, then after 30 minutes 100 mg/kg gentamicin was injected intramuscularly for 10 days). Blood samples were collected for biochemical analyses, kidney tissue samples were collected for light, electron microscopic and immunohistochemical investigations. In gentamicin group glomerular degeneration, tubular dilatation, vacuolization, desquamation of tubular cells and hyaline cast formation in luminal space and leukocyte infiltration were seen. Disorganization of microvilli of tubular cells, apical cytoplasmic blebbing, lipid accumulation, myelin figure like structure formation, increased lysosomes, mitochondrial swelling and disorganization of cristae structures, apoptotic changes and widening of intercellular space were found. TNF-α, IL-6 and caspase 3 expressions were increased. BUN and creatinine concentrations were increased. Increase in MDA levels and decrease in SOD activities were determined. Even though degeneration still continues in gentamicin+2-APB treatment group, severity and the area it occupied were decreased and the glomerular and tubule structures were generally preserved. TNF-α, IL-6, caspase 3 immunoreactivities and BUN, creatinine, MDA concentrations were reduced and SOD activities were increased markedly compared to gentamicin group. In conclusion, it has been considered that 2-APB can prevent gentamicin mediated nephrotoxicity with its anti-oxidant, anti-apoptotic and anti-inflammatory effects.

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2-氨基乙氧基二苯硼酸酯(2-APB)对氨基糖苷肾毒性的影响。
研究瞬时受体电位通道调节剂2-氨基乙氧基二苯硼酸盐(2-APB)对活性氧、钙诱导的细胞凋亡和炎症引起的氨基糖苷肾毒性的保护作用。Wistar大鼠40只(n=8),随机分为:对照组;DMSO组;2-APB组;庆大霉素组(肌肉注射庆大霉素100 mg/kg,持续10 d);庆大霉素+ 2- apb组(腹腔注射2 mg/kg 2- apb, 30 min后肌肉注射100 mg/kg庆大霉素,持续10 d)。采集血液样本进行生化分析,采集肾脏组织样本进行光镜、电镜和免疫组化检查。庆大霉素组可见肾小球变性、小管扩张、空泡化、小管细胞脱屑、管腔内透明样样形成及白细胞浸润。小管细胞微绒毛紊乱,顶端胞浆泡状,脂质堆积,髓鞘图状结构形成,溶酶体增多,线粒体肿胀,嵴结构紊乱,细胞凋亡改变,细胞间隙增宽。TNF-α、IL-6、caspase 3表达升高。BUN和肌酐浓度升高。MDA水平升高,SOD活性降低。庆大霉素+2-APB治疗组尽管变性仍在继续,但其严重程度和占地面积均有所降低,肾小球和小管结构基本保留。与庆大霉素组相比,TNF-α、IL-6、caspase 3免疫反应活性和BUN、肌酐、MDA浓度显著降低,SOD活性显著升高。综上所述,2-APB具有抗氧化、抗凋亡和抗炎作用,可预防庆大霉素介导的肾毒性。
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来源期刊
Ultrastructural Pathology
Ultrastructural Pathology 医学-病理学
CiteScore
2.00
自引率
10.00%
发文量
40
审稿时长
6-12 weeks
期刊介绍: Ultrastructural Pathology is the official journal of the Society for Ultrastructural Pathology. Published bimonthly, we are the only journal to be devoted entirely to diagnostic ultrastructural pathology. Ultrastructural Pathology is the ideal journal to publish high-quality research on the following topics: Advances in the uses of electron microscopic and immunohistochemical techniques Correlations of ultrastructural data with light microscopy, histochemistry, immunohistochemistry, biochemistry, cell and tissue culturing, and electron probe analysis Important new, investigative, clinical, and diagnostic EM methods.
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