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Sildenafil and tadalafil reduce the risk of contrast-induced nephropathy by modulating the oxidant/antioxidant balance in a murine model.
Food and Chemical Toxicology ( IF 3.9 ) Pub Date : 2019-12-09 , DOI: 10.1016/j.fct.2019.111038
Andrei Mihai Iordache 1 , Anca Oana Docea 2 , Ana Maria Buga 3 , Ovidiu Zlatian 4 , Marius Eugen Ciurea 5 , Otilia Constantina Rogoveanu 6 , Florin Burada 7 , Simona Sosoi 7 , Radu Mitrut 8 , Charalampos Mamoulakis 9 , Dana Albulescu 10 , Ramona Constantina Vasile 11 , Aristides Tsatsakis 12 , Daniela Calina 1
Affiliation  

The aim of the study was to evaluate the potential protective role of sildenafil and tadalafil in contrast-induced nephropathy (CIN) by modulating oxidative stress. Thirty Wistar male rats were equally assigned into five groups: sham, CIN, CIN + sildenafil (10 mg/kg bw/day), CIN + tadalafil (5 mg/kg bw/day) and CIN + N-Acetyl Cysteine (NAC) (100 mg/kg bw/day) as a positive control. CIN was induced by 12 h dehydration and administration of indomethacin (10 mg/kg bw), N-ω- nitro-L-arginine methyl ester (10 mg/kg bw), and iopromide (3 g/kg bw iodine). Blood was drawn prior to and 24 h after CIN induction for evaluating renal function and oxidative stress. In the CIN group, total antioxidant capacity (TAC), reduced glutathione (GSH) and catalase (CAT) levels were significantly decreased; and protein carbonyl (PROTC) and thiobarbituric reactive species (TBARS) were significantly increased compared to the sham group. Pre- Sildenafil and tadalafil pre-treatment reduced CIN risk and reversed oxidative stress almost to the sham group levels. These results suggest that PDE5Is can be good candidates for preventing CIN based on their ability to modulate the oxidant/antioxidant balance.

中文翻译:

西地那非和他达拉非通过调节鼠模型中的氧化剂/抗氧化剂平衡来降低造影剂诱发的肾病的风险。

该研究的目的是通过调节氧化应激来评估西地那非和他达拉非在对比剂诱发的肾病(CIN)中的潜在保护作用。将30只Wistar雄性大鼠平均分为五组:假手术,CIN,CIN +西地那非(10 mg / kg bw /天),CIN +他达拉非(5 mg / kg bw /天)和CIN + N-乙酰半胱氨酸(NAC) (100 mg / kg bw /天)作为阳性对照。通过脱水12小时并给予消炎痛(10 mg / kg bw),N-ω-硝基-L-精氨酸甲酯(10 mg / kg bw)和碘普罗胺(3 g / kg bw碘)诱导CIN。在CIN诱导之前和之后24小时抽血以评估肾功能和氧化应激。在CIN组中,总抗氧化剂能力(TAC),还原型谷胱甘肽(GSH)和过氧化氢酶(CAT)含量显着降低。与假手术组相比,蛋白羰基(PROTC)和硫代巴比妥反应性物种(TBARS)显着增加。西地那非和他达拉非前处理可降低CIN风险,并将氧化应激逆转至假组水平。这些结果表明,基于PDE5I调节氧化剂/抗氧化剂平衡的能力,它们可能是预防CIN的良好候选者。
更新日期:2019-12-09
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