Abstract
Oxidative stress may represent a common link between chronic liver damage and hepatic fibrosis. Antioxidants and interferon seem to protect against hepatic stellate cell (HSC) activation and liver fibrosis. This study evaluated (1) the effect of the profibrotic agent dimethylnitrosamine (DMN) on the hepatic oxidative balance in the rat; (2) the role played by the antioxidant agent N-acetylcysteine (NAC); and (3) the antifibrotic effects of two different types of interferon-α: recombinant alpha-2b (rIFN-α) and leukocyte alpha (LeIFN-α). Five groups of rats received: (1) saline; (2) DMN; (3) DMN + NAC; (4) DMN + rIFN-α; and (5) DMN + LeIFN-α. Oxidative balance was evaluated by hepatic glutathione, TBARs, protein carbonyl, and sulfhydryl determination. Fibrosis was determined by hepatic hydroxyproline content and fibronectin (FN) staining (immunohistochemistry). DMN rats showed a diffuse FN deposition, an impaired oxidative balance, and higher hepatic hydroxyproline levels compared to that of controls. NAC administration significantly reduced FN deposition, increased hepatic glutathione, and decreased TBARs and protein carbonyls. Administration of IFN-α exerted different effects according to the type used. Both IFNs decreased FN deposition; however, LeIFN-α significantly improved histology and oxidative parameters compared to those of untreated DMN and rats treated with rIFN-α. This study shows the role of free radicals in this model of hepatic fibrosis; the protective effect of NAC against liver fibrosis; and the antifibrotic effect exerted by IFN-α (particularly LeIFN-α) independent of its antiviral activity.
| Original language | English |
|---|---|
| Pages (from-to) | 130-139 |
| Number of pages | 10 |
| Journal | Toxicology and Applied Pharmacology |
| Volume | 175 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Sep 1 2001 |
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Keywords
- Dimethylnitrosamine
- Interferon
- Liver fibrosis
- N-acetylcysteine
- Oxidative balance
ASJC Scopus subject areas
- Pharmacology
- Toxicology
Cite this
Increased oxidative stress in dimethylnitrosamine-induced liver fibrosis in the rat : Effect of N-acetylcysteine and interferon-α. / Vendemiale, Gianluigi; Grattagliano, Ignazio; Caruso, Maria Lucia; Serviddio, Gaetano; Valentini, Anna Maria; Pirrelli, Michele; Altomare, Emanuele.
In: Toxicology and Applied Pharmacology, Vol. 175, No. 2, 01.09.2001, p. 130-139.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Increased oxidative stress in dimethylnitrosamine-induced liver fibrosis in the rat
T2 - Effect of N-acetylcysteine and interferon-α
AU - Vendemiale, Gianluigi
AU - Grattagliano, Ignazio
AU - Caruso, Maria Lucia
AU - Serviddio, Gaetano
AU - Valentini, Anna Maria
AU - Pirrelli, Michele
AU - Altomare, Emanuele
PY - 2001/9/1
Y1 - 2001/9/1
N2 - Oxidative stress may represent a common link between chronic liver damage and hepatic fibrosis. Antioxidants and interferon seem to protect against hepatic stellate cell (HSC) activation and liver fibrosis. This study evaluated (1) the effect of the profibrotic agent dimethylnitrosamine (DMN) on the hepatic oxidative balance in the rat; (2) the role played by the antioxidant agent N-acetylcysteine (NAC); and (3) the antifibrotic effects of two different types of interferon-α: recombinant alpha-2b (rIFN-α) and leukocyte alpha (LeIFN-α). Five groups of rats received: (1) saline; (2) DMN; (3) DMN + NAC; (4) DMN + rIFN-α; and (5) DMN + LeIFN-α. Oxidative balance was evaluated by hepatic glutathione, TBARs, protein carbonyl, and sulfhydryl determination. Fibrosis was determined by hepatic hydroxyproline content and fibronectin (FN) staining (immunohistochemistry). DMN rats showed a diffuse FN deposition, an impaired oxidative balance, and higher hepatic hydroxyproline levels compared to that of controls. NAC administration significantly reduced FN deposition, increased hepatic glutathione, and decreased TBARs and protein carbonyls. Administration of IFN-α exerted different effects according to the type used. Both IFNs decreased FN deposition; however, LeIFN-α significantly improved histology and oxidative parameters compared to those of untreated DMN and rats treated with rIFN-α. This study shows the role of free radicals in this model of hepatic fibrosis; the protective effect of NAC against liver fibrosis; and the antifibrotic effect exerted by IFN-α (particularly LeIFN-α) independent of its antiviral activity.
AB - Oxidative stress may represent a common link between chronic liver damage and hepatic fibrosis. Antioxidants and interferon seem to protect against hepatic stellate cell (HSC) activation and liver fibrosis. This study evaluated (1) the effect of the profibrotic agent dimethylnitrosamine (DMN) on the hepatic oxidative balance in the rat; (2) the role played by the antioxidant agent N-acetylcysteine (NAC); and (3) the antifibrotic effects of two different types of interferon-α: recombinant alpha-2b (rIFN-α) and leukocyte alpha (LeIFN-α). Five groups of rats received: (1) saline; (2) DMN; (3) DMN + NAC; (4) DMN + rIFN-α; and (5) DMN + LeIFN-α. Oxidative balance was evaluated by hepatic glutathione, TBARs, protein carbonyl, and sulfhydryl determination. Fibrosis was determined by hepatic hydroxyproline content and fibronectin (FN) staining (immunohistochemistry). DMN rats showed a diffuse FN deposition, an impaired oxidative balance, and higher hepatic hydroxyproline levels compared to that of controls. NAC administration significantly reduced FN deposition, increased hepatic glutathione, and decreased TBARs and protein carbonyls. Administration of IFN-α exerted different effects according to the type used. Both IFNs decreased FN deposition; however, LeIFN-α significantly improved histology and oxidative parameters compared to those of untreated DMN and rats treated with rIFN-α. This study shows the role of free radicals in this model of hepatic fibrosis; the protective effect of NAC against liver fibrosis; and the antifibrotic effect exerted by IFN-α (particularly LeIFN-α) independent of its antiviral activity.
KW - Dimethylnitrosamine
KW - Interferon
KW - Liver fibrosis
KW - N-acetylcysteine
KW - Oxidative balance
UR - http://www.scopus.com/inward/record.url?scp=0035449657&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035449657&partnerID=8YFLogxK
U2 - 10.1006/taap.2001.9234
DO - 10.1006/taap.2001.9234
M3 - Article
C2 - 11543645
AN - SCOPUS:0035449657
VL - 175
SP - 130
EP - 139
JO - Toxicology and Applied Pharmacology
JF - Toxicology and Applied Pharmacology
SN - 0041-008X
IS - 2
ER -