N-acetylcysteine attenuates kidney injury in rats subjected to renal ischaemia-reperfusion.
BACKGROUND
The aim of the present study is to examine the effects of N-acetylcysteine (NAC), a thiol-containing anti-oxidant, on renal function and morphology, and biomarkers of oxidative stress, in rats subjected to renal ischaemia-reperfusion (IR).


METHODS
Sprague-Dawley rats underwent unilateral nephrectomy and either contralateral renal IR (40 min of renal arterial clamping), or sham manipulation. Treatment groups were: (1) IR-Saline, (2) IR-NAC, (3) Sham-Saline and (4) Sham-NAC. The N-acetylcysteine was administered in a dose of 200 mg/kg intraperitoneally at 24, 12 and 2 h before, and 24, 48 and 72 h after, renal IR. Plasma creatinine was measured on days 1, 3 and 7 after IR, and kidney histology was assessed on day 7. In separate groups of animals we measured renal levels of the anti-oxidant glutathione, markers of systemic oxidative stress (plasma ascorbyl radical, urinary 8-iso-prostaglandin F2alpha), and glomerular filtration rate (GFR) by 51Cr-EDTA clearance, on day 1 after renal IR.


RESULTS
Treatment with NAC ameliorated the decline in GFR and reduced hyperkalaemia on day 1 (P<0.05), lowered plasma creatinine levels on days 1 and 3 (P<0.05), and decreased renal interstitial inflammation on day 7 (P<0.05), after renal IR. Kidney glutathione levels decreased significantly in group IR-Saline in response to IR (P<0.05), but were completely repleted in group IR-NAC. Groups with renal IR injury and acute renal failure showed increased plasma ascorbyl radical levels, and elevated urinary 8-iso-prostaglandin F2alpha excretion, compared with sham (P<0.05). N-acetylcysteine treatment reduced plasma ascorbyl concentrations 24 h after renal IR (P<0.05), but had no effect on the rate of urinary 8-iso-prostaglandin F2alpha excretion.


CONCLUSIONS
N-acetylcysteine improves kidney function, and reduces renal interstitial inflammation, in rats subjected to renal IR. These effects were associated with increased renal glutathione levels, and decreased plasma ascorbyl concentrations, suggesting that NAC attenuates renal and systemic oxidative stress in this model.
Nitescu
Nicoletta
N
Department of Anaesthesiology and Intensive Care, Institute of Surgical Sciences, The Sahlgrenska Academy at Göteborg University, Sahlgrenska University Hospital, S-413 45 Göteborg, Sweden. nicoletta.nitescu@vgregion.se
Ricksten
Sven-Erik
SE
Marcussen
Niels
N
Haraldsson
Börje
B
Nilsson
Ulf
U
Basu
Samar
S
Guron
Gregor
G
D000111:Acetylcysteine / Q000494:pharmacology*; D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000473:pathology; D000704:Analysis of Variance; D000818:Animals; D001707:Biopsy, Needle; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D005919:Glomerular Filtration Rate / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012079:Renal Circulation / Q000187:drug effects; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D018709:Statistics, Nonparametric
D003404:Creatinine; D005978:Glutathione; D000111:Acetylcysteine