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Phosphodiesterase-5 inhibitors ameliorate structural kidney damage in a rat model of contrast-induced nephropathy.
Food and Chemical Toxicology ( IF 4.3 ) Pub Date : 2020-07-02 , DOI: 10.1016/j.fct.2020.111535
Andrei Mihai Iordache 1 , Ana Maria Buga 2 , Dana Albulescu 3 , Ramona Constantina Vasile 4 , Radu Mitrut 5 , George Georgiadis 6 , Ioannis-Erineos Zisis 6 , Charalampos Mamoulakis 7 , Aristidis Tsatsakis 8 , Anca Oana Docea 9 , Daniela Calina 1
Affiliation  

The aim of the study was to investigate the potential of sildenafil and tadalafil to ameliorate structural kidney damage in contrast-induced nephropathy (CIN). A rat model of CIN was developed by dehydration, administration of a nitric oxide inhibitor and a prostaglandin synthesis inhibitor (L-NAME/indomethacin) and contrast media exposure to iopromide. The effect of pre-treatment with sildenafil, tadalafil or N-acetyl cysteine (NAC) for 7 days prior to CIN induction was investigated. All animals were sacrificed at 24 h after CIN induction and both kidneys were collected. Histopathological examination was performed under light microscopy in serial tissue sections stained with hematoxylin and eosin. CIN group showed hydropic changes of the renal tubules (proximal and distal convoluted tubules and Henle's loop), an increased Bowman space with lobulated glomerulus and alteration of macula densa region of distal convolute tubules. The groups pretreated with sildenafil and tadalafil showed nearly normal histological aspects of renal tissue. The group pretreated with NAC showed similar but less intense histopathologic changes compared to CIN group. Sildenafil and tadalafil pre-treatment ameliorates CIN-related structural kidney damage and the protective potential of these agents is superior to NAC.



中文翻译:

磷酸二酯酶5抑制剂可减轻对比剂诱发的肾病大鼠模型的肾脏结构损害。

该研究的目的是研究西地那非和他达拉非改善造影剂诱发的肾病(CIN)中肾脏结构损害的潜力。通过脱水,给予一氧化氮抑制剂和前列腺素合成抑制剂(L-NAME /吲哚美辛)以及造影剂暴露于碘普罗胺来开发CIN大鼠模型。研究了在CIN诱导前用西地那非,他达拉非或N-乙酰半胱氨酸(NAC)预处理7天的效果。CIN诱导后24小时处死所有动物,并收集两个肾脏。在光学显微镜下对经苏木精和曙红染色的连续组织切片进行组织病理学检查。CIN组显示肾小管(近端和远端的曲折小管和Henle's loop)发生水肿性改变,鲍曼间隙增大,肾小球小叶化,远端回旋小管黄斑区改变。用西地那非和他达拉非预处理的组显示出几乎正常的肾脏组织学方面。与CIN组相比,经NAC预处理的组显示出相似但较不强烈的组织病理学改变。西地那非和他达拉非预处理可改善CIN相关的肾脏结构损害,这些药物的保护潜力优于NAC。

更新日期:2020-07-07
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