Publication: Ultrastructural evaluation of the effect of N-acetylcysteine on methotrexate nephrotoxicity in rats
Authors
Çaglar, Yıdız ; Özgür, Hülya ; Matur, Irem ; Yenilmez, Ebru Dündar ; Tuli, Abdullah ; Gönlüsen, Gülfiliz ; Polat, Sait
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Publisher
F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología
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DOI
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info:eu-repo/semantics/article
Description
Abstract
The aim of this study is to investigate the
possible protective effect of N-Acetylcysteine (NAC)
against the likely methotrexate (MTX) toxicity on the
kidney using ultrastructural together with biochemical
data. Moreover, the immunohistochemical detection of
Ki67 nuclear antigen is to be evaluated. Fifteen male
Wistar albino rats, weighing 240-290 g, were divided
into three equal groups: Rats receiving MTX alone, rats
receiving MTX plus NAC treatment, and rats comprising
the control group. MTX (18 mg/kg/day, body weight) in
dissolved physiologic saline was administered
intraperitoneally to rats during 3 days. For the MTX plus
NAC group, N-Acetylcysteine (300 mg/kg/day, body
weight) was administered together with MTX. At the
end of the third day, all the rats were killed with cervical
dislocation to obtain blood and tissue samples.
Application of MTX principally induced prominent large
vacuolization in the proximal convoluted tubule cells,
and focal thickening in the glomerular basal lamina of
some glomeruli. A decrease in tissue SOD (superoxide
dismutase) and GSH-Px (glutathione peroxidase), and an
increase in serum urea nitrogen and creatinine and in
tissue MDA (malondialdehyde) levels were also seen in
the MTX group. These changes were significantly
reversed in the MTX-plus-NAC-treated group. Most of
the vacuoles in the proximal convoluted tubule cells
disappeared. Furthermore, an increase in antioxidant
enzyme activities, a decrease in serum urea nitrogen and
creatinine, and tissue MDA levels were all significant.
Additionally, an increase in the number of Ki67 positive-
stained cells in proximal tubules was also noted. In
conclusion, NAC may be a promising substance against
MTX-induced renal damage. It might be useful to use
NAC supplementally to minimize MTX-induced
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Citation
Histology and Histopathology, vol. 28, nº 7 (2013)
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