N-Acetyl-l-Cysteine Ameliorations RenalFunction Early After Renal Ischemia and Reperfusion; it is not Protective over a LongTerm under a High-Sodium Diet in Rats

IF 0.4 Q4 PHARMACOLOGY & PHARMACY Journal of Pharmacology & Pharmacotherapeutics Pub Date : 2023-08-08 DOI:10.1177/0976500x231189327
R. C. Pereira, C. Romão, Beatriz Santos Geoffroy Corrêa, W. Dominguez, L. Furukawa
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Abstract

To evaluate the early and late effects of N-acetyl-l-cysteine (NAC) treatment on renal ischemia and reperfusion (I/R) insult in adult Wistar rats influenced by chronic high sodium (HS) intake. Adult male Wistar rats (8 weeks of age) received an HS (8.0% NaCl) or normal sodium (NS; 1.3% NaCl) diet and NAC (600 mg/L) in drinking water or normal water. At 11 weeks of age, the rats underwent a renal I/R procedure. They followed for 10 weeks after I/R, at the 1st, 2nd, 4th, and 10th weeks, in which tail blood pressure (tBP) and renal function were evaluated. And renal renin gene expression was evaluated in the 10th week after I/R. During the study, it was observed that the tBP remained consistently higher in the HS-I/R+water group compared to the NS-I/R+water group. However, in the early weeks following I/R (1st, 2nd, and 4th weeks), the tBP was lower in the HS-I/R+NAC group than in the HS-I/R+water group. In the 10th week after I/R, the serum creatinine levels were higher in both the HS-I/R+NAC and NS-I/R+NAC groups compared to the HS-I/R+water and NS-I/R+water groups. Conversely, the creatinine clearance was higher in the HS-I/R+NAC group than in the HS-I/R+ group in the 2nd week following I/R. Additionally, the urinary protein levels were higher in the HS-I/R+NAC group than in the NS-I/R+NAC group in the 10th week after I/R. It was also observed that NAC treatment resulted in increased renal renin gene expression in the 10th week following I/R. After renal I/R in animals given HS, NAC treatment was initially effective in lowering blood pressure or increasing creatinine clearance. However, these positive effects did not persist over the long term, resulting in decreased kidney function and increased blood pressure. Furthermore, the renin-angiotensin-aldosterone system was increased by HS intake, and the benefits of the NS diet were less effective than those of the HS diet. Thus, NAC provides temporary protection only in the early stages following an insult.
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n -乙酰-l-半胱氨酸对肾缺血再灌注早期肾功能的改善作用长期高钠饮食对大鼠没有保护作用
探讨n -乙酰半胱氨酸(NAC)治疗对慢性高钠(HS)所致成年Wistar大鼠肾缺血再灌注(I/R)损伤的早期和晚期影响。成年雄性Wistar大鼠(8周龄)给予HS (8.0% NaCl)或正常钠(NS;1.3% NaCl)日粮和NAC (600 mg/L)在饮用水或正常水中。在11周龄时,大鼠进行肾脏I/R手术。I/R后随访10周,分别于第1、2、4、10周,评估尾血压(tBP)和肾功能。在I/R后第10周检测肾素基因表达。在研究过程中,观察到HS-I/R+水组的tBP始终高于NS-I/R+水组。然而,在I/R后的前几周(第1、2和4周),HS-I/R+NAC组的tBP低于HS-I/R+水组。I/R后第10周,HS-I/R+NAC组和NS-I/R+NAC组血清肌酐水平均高于HS-I/R+水组和NS-I/R+水组。相反,在I/R后第2周,HS-I/R+NAC组的肌酐清除率高于HS-I/R+组。此外,在I/R后第10周,HS-I/R+NAC组的尿蛋白水平高于NS-I/R+NAC组。还观察到NAC治疗导致I/R后第10周肾素基因表达增加。在给予HS的动物肾脏I/R后,NAC治疗最初在降低血压或增加肌酐清除率方面有效。然而,这些积极作用并没有长期持续,导致肾功能下降和血压升高。此外,高脂饮食增加了肾素-血管紧张素-醛固酮系统,高脂饮食的效果不如高脂饮食。因此,NAC仅在遭受侮辱后的早期阶段提供临时保护。
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