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

• Published in: Journal of pharmacology & pharmacotherapeutics 2023-06, Vol.14 (2), p.142-152
• Main Authors: Pereira, Rafael Canavel, Romão, Carolina Martinez, Corrêa, Beatriz Santos Geoffroy, Dominguez, Wagner Vasques, Furukawa, Luzia Naôko Shinohara
• Format: Article
• Language: English
• Subjects: Blood pressure; Creatinine; Gene expression; Ischemia
• ISSN: 0976-500X; 0976-5018
• DOI: 10.1177/0976500X231189327

Objectives 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. Materials and Methods 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. Results 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. Conclusion 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.