title: N-acetylcysteine attenuates renal alterations induced by senescence in the rat.
abstract: The aim of this study was to evaluate the effects of N-acetylcysteine (NAC) on renal function, as well as on sodium and water transporters, in the kidneys of aged rats. Normal, 8-month-old male Wistar rats were treated (n=6) or not (n=6) with NAC (600 mg/L in drinking water) and followed for 16 months. At the end of the follow-up period, we determined inulin clearance, serum thiobarbituric acid reactive substances (TBARS), serum cholesterol, and urinary phosphate excretion. In addition, we performed immunohistochemical staining for p53 and for ED-1-positive cells (macrophages/monocytes), together with Western blotting of kidney tissue for NKCC2, aquaporin 2 (AQP2), urea transporter A1 (UT-A1) and Klotho protein. At baseline, the two groups were similar in terms of creatinine clearance, proteinuria, cholesterol, and TBARS. At the end of the follow-up period, NAC-treated rats presented greater inulin clearance and reduced proteinuria, as well as lower serum cholesterol, serum TBARS, and urinary phosphate excretion, in comparison with untreated rats. In addition, NAC-treated rats showed upregulated expression of NKCC2, AQP2, and UT-A1; elevated Klotho protein expression, low p53 expression, and few ED-1 positive cells. In conclusion, we attribute these beneficial effects of NAC (the significant improvements in inulin clearance and in the expression of NKCC2, AQP2, and UT-A1) to its ability to decrease oxidative stress, inhibit p53 expression, minimize kidney inflammation, and stimulate Klotho expression.
authors.affiliation: Laboratory for Medical Research, Nephrology Department, University of São Paulo School of Medicine, São Paulo, Brazil.
authors.forename: Maria Heloisa M
authors.initials: MH
authors.lastname: Shimizu
authors.forename: Rildo A
authors.initials: RA
authors.lastname: Volpini
authors.forename: Ana Carolina
authors.initials: AC
authors.lastname: de Bragança
authors.forename: Renata
authors.initials: R
authors.lastname: Campos
authors.forename: Daniele
authors.initials: D
authors.lastname: Canale
authors.forename: Talita R
authors.initials: TR
authors.lastname: Sanches
authors.forename: Lúcia
authors.initials: L
authors.lastname: Andrade
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Seguro
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000367:Age Factors; D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D051399:Aquaporin 2 / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D016922:Cellular Senescence; D002784:Cholesterol / Q000097:blood; D053331:Ectodysplasins / Q000378:metabolism; D005966:Glucuronidase / Q000378:metabolism; D007150:Immunohistochemistry; D007444:Inulin / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D000090265:Klotho Proteins; D008297:Male; D026901:Membrane Transport Proteins / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010710:Phosphates / Q000652:urine; D051381:Rats; D017208:Rats, Wistar; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism; D064466:Solute Carrier Family 12, Member 1; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D000096982:Urea Transporters
chemical_list: D000111:Acetylcysteine; D000975:Antioxidants; D051399:Aquaporin 2; D015415:Biomarkers; D002784:Cholesterol; D053331:Ectodysplasins; D005966:Glucuronidase; D007444:Inulin; D000090265:Klotho Proteins; D026901:Membrane Transport Proteins; D010710:Phosphates; D028021:Sodium-Potassium-Chloride Symporters; D064466:Solute Carrier Family 12, Member 1; D017392:Thiobarbituric Acid Reactive Substances; D016159:Tumor Suppressor Protein p53; D000096982:Urea Transporters; C496025:Aqp2 protein, rat; C578716:Slc12a1 protein, rat