Magnesium supplementation combined with N-acetylcysteine protects against postischemic acute renal failure.
Magnesium is a potent vasodilator whose effects have not been evaluated in renal ischemia. The antioxidant properties of N-acetylcysteine (NAC) partially protect animals from ischemic/reperfusion injury. This study was designed to evaluate magnesium supplementation, alone or combined with NAC, on ischemic acute renal failure. Rats were maintained on normal diets, supplemented or not with MgCl(2).6H(2)O (1% in drinking water) for 23 d, and some rats received NAC (440 mg/kg body wt) on days 20 to 23. On day 21, ischemia was induced by clamping both renal arteries for 30 min. Five groups were studied: Normal, ischemia, ischemia+magnesium, ischemia+NAC, and ischemia+magnesium+NAC. GFR (inulin clearance), renal blood flow (RBF), FEH(2)O, and FENa were determined. Serum magnesium was decreased in ischemia-only rats. Magnesium prevented postischemia GFR and RBF decreases but did not protect against tubular damage. However, NAC completely restored the tubular damage induced by ischemia/reperfusion. Semiquantitative immunoblotting showed that NAC prevented the decreased expression of Na-K-2Cl co-transporter and aquaporin 2 after renal ischemia/reperfusion. Untreated rats with acute renal failure demonstrated markedly decreased endothelial nitric oxide synthase expression. Significantly, treatment with NAC, magnesium, or both completely inhibited downregulation of endothelial nitric oxide synthase. The tubular necrosis scores were lower in rats that were treated with NAC alone or with the magnesium-NAC combination. Magnesium prevented postischemia GFR and RBF decreases but did not protect against tubular damage. The NAC protected tubules from ischemia, decreased infiltrating macrophages/lymphocytes, and had a mild protective effect on GFR. In ischemic/reperfusion injury, renal function benefits more from the magnesium-NAC combination than from magnesium alone.
de Araujo
Magali
M
Department of Nephrology, Laboratory of Basic Research, University of São Paulo School of Medicine, São Paulo, Brazil.
Andrade
Lucia
L
Coimbra
Terezila M
TM
Rodrigues
Adilson C
AC
Seguro
Antonio Carlos
AC
D000111:Acetylcysteine / Q000008:administration & dosage / Q000627:therapeutic use*; D058186:Acute Kidney Injury / Q000517:prevention & control*; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D019587:Dietary Supplements; D004195:Disease Models, Animal; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007511:Ischemia / Q000517:prevention & control; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D015636:Magnesium Chloride / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology*
D015636:Magnesium Chloride; D052250:Nitric Oxide Synthase Type III; D000111:Acetylcysteine