Could nephrotoxicity due to colistin be ameliorated with the use of N-acetylcysteine?
OBJECTIVE
The protective effect of N-acetylcysteine (NAC) on nephrotoxicity due to contrast nephropathy and reperfusion-induced ischemia has been reported in experimental models. However, its efficacy on colistin-induced nephrotoxicity has not been elucidated yet. The primary aim of this study was to evaluate the nephrotoxic effect of colistin and to investigate the possible protective effect of NAC on colistin-induced nephrotoxicity. The secondary aim was to research the systemic effects of nephrotoxicity-induced oxidative stress on the lung.


METHODS
Eighteen female Sprague-Dawley rats were randomly assigned and were given (a) 1 ml/kg sterile saline, (b) 300,000 IU/kg/day colistin, and (c) 300,000 IU/kg/day colistin and 150 mg/kg NAC for six consecutive days.


RESULTS
Plasma blood urea nitrogen (BUN), creatinine, urinary creatinine, urinary protein, plasma TNF-alpha levels, renal tissue superoxide dismutase (SOD) and malondialdehyde (MDA) activity and immunocytochemical findings were evaluated. Colistin exerted nephrotoxicity and achieved a significant increase in plasma BUN and creatinine levels and renal tissue SOD levels. NAC exhibited no significant effect on biochemical parameters but reduced renal tissue SOD level and reversed immunocytochemical staining of inducible nitric oxide synthase (i-NOS) and neurotrophin-3. Increased oxidative stress in the lung tissue of the rats treated with colistin has also been documented. Additionally, NAC significantly reduced the immunostaining of endothelial NOS (e-NOS) and i-NOS in the lung tissue.


CONCLUSIONS
Colistin-induced renal toxicity may be attributable to oxidative damage. The combined treatment of colistin plus NAC seems to have a beneficial role in restoration of the oxidant injury which may be related to its antioxidant effect.
Ozyilmaz
Ezgi
E
Department of Pulmonary Disease, Cukurova University Faculty of Medicine, Balcali, 01320 Adana, Turkey. ezgiozyilmaz@hotmail.com
Ebinc
Fatma Ayerden
FA
Derici
Ulver
U
Gulbahar
Ozlem
O
Goktas
Guleser
G
Elmas
Cigdem
C
Oguzulgen
I Kivilcim
IK
Sindel
Sukru
S
D000111:Acetylcysteine / Q000627:therapeutic use*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D003091:Colistin / Q000633:toxicity*; D005260:Female; D007674:Kidney Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control*; D008168:Lung / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley
D000900:Anti-Bacterial Agents; D000111:Acetylcysteine; D003091:Colistin