Effect of N-acetylcysteine on blood and tissue lipid peroxidation in lipopolysaccharide-induced obstructive jaundice.
In obstructive jaundice, free radical production is increased and antioxidative activity is reduced. N-Acetylcysteine (NAC) has a beneficial effect with anti-inflammatory and antioxidant activity, acting as a free radical scavenger. NAC inhibits inducible nitric oxide synthase, suppresses cytokine expression/release, and inhibits adhesion molecule expression and nuclear factor kappa B. The aim of this study was to investigate the effects of NAC on liver/renal tissue and serum lipid peroxidation in lipopolysaccharide (LPS)-induced obstructive jaundice. We randomized 60 rats into 6 groups: group 1, Sham; group 2, obstructive jaundice (OJ) induced after bile-duct ligation; group 3, OJ + NAC (100 mg kg- 1 subcutaneously); group 4, OJ + LPS (10 mg kg-1); group 5, OJ + NAC + LPS; and group 6, OJ + LPS + NAC. For each group, the biochemical markers of lipid peroxidation and the antioxidant products were measured in serum and liver/renal tissue after sacrifice. Almost all lipid peroxidation products levels were increased and antioxidant products levels were decreased in groups who received LPS (groups 4, 5, and 6), but the effect was less remarkable when NAC was administered before LPS (group 5). The same trend was seen for groups with OJ +/- LPS who did not received NAC or received it after induced toxemia (groups 2, 4, and 6) as compared to groups 1 and 3. Moreover, in the case of OJ + LPS, rats treated with NAC before LPS (group 5) had lower lipid peroxidation products levels and higher antioxidant products levels as compared to those who did not received NAC (group 4). This phenomenon was not reproducible with NAC administered after LPS (group 6). Thus, results of this study showed that NAC prevents the deleterious effects of LPS in obstructive jaundice by reducing lipid peroxidation in serum and liver/renal tissue if administered before LPS. Nonetheless, NAC failed to prevent the lipid peroxidation in the case of established endotoxemia in obstructive jaundice.
Caglikulekci
Mehmet
M
Department of General Surgery, Mersin University Medical School, Mersin, Turkey. mcaglikulecki@yahoo.com
Dirlik
Musa
M
Pata
Cengiz
C
Plasse
Marylene
M
Tamer
Lulufer
L
Ogetman
Zekai
Z
Ercan
Bahadir
B
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D001205:Ascorbic Acid / Q000097:blood; D001652:Bile Ducts; D004912:Erythrocytes / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D041781:Jaundice, Obstructive / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D008026:Ligation; D015227:Lipid Peroxidation / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D016166:Free Radical Scavengers; D008070:Lipopolysaccharides; D017392:Thiobarbituric Acid Reactive Substances; D008315:Malondialdehyde; D000254:Sodium-Potassium-Exchanging ATPase; D005978:Glutathione; D001205:Ascorbic Acid; D000111:Acetylcysteine