Beneficial effects of N-acetylcysteine on sodium taurocholate-induced pancreatitis in rats.
BACKGROUND
Acute pancreatitis (AP) is a complex disease associated with significant complications and a high rate of mortality. Although several mechanisms are put forward, oxidative stress seems the most important early event in the pathophysiology of AP. Therefore, we evaluated the beneficial effects of N-acetylcysteine (NAC), a strong antioxidant, in experimental AP.


METHODS
Forty-nine Sprague-Dawley rats were used. Acute pancreatitis (AP) was induced by the intraductal infusion of sodium taurocholate. Rats were divided into seven groups (each containing seven rats): control, sham-operated (saline-treated, 3.5 and 12 h), non-treated AP (3.5 and 12 h) and NAC-treated AP (3.5 and 12 h). Treated rats received intraperitoneal (i.p.) NAC 1000 mg/kg 24 h before and just before the induction of pancreatitis.


RESULTS
Rats with AP had extensive parenchymal and fat necrosis and NAC treatment at 12 h reduced tissue necrosis significantly (P < 0.05). NAC treatment at 12 h reduced leukocytic infiltration significantly (P < 0.05). Edema and hemorrhage were significantly increased in the AP groups when compared to controls (P < 0.001). NAC treatment reduced edema and hemorrhage at both 3.5 and 12 h slightly but not significantly. The total pathological mean score was significantly increased in the AP groups (P < 0.05) and it was reduced by NAC treatment (P < 0.05). NAC treatment decreased plasma amylase and lipase levels significantly (P < 0.05). While glutathione peroxidase (GPx) activity of pancreatic tissue was similar in the NAC-treated and AP groups, hepatic tissue GPx activity was lower in the AP groups, and NAC treatment restored it (P < 0.05). NAC had no effect on pancreatic superoxide dismutase level. In the NAC-treated rats, the serum NO(2)/NO(3) (nitrite/nitrate) level was significantly increased in the 3.5-h group when compared to the respective AP group (P < 0.05). NAC treatment also significantly reduced the serum concentration of the lipid peroxidation product, malondialdehyde, at 12 h (P < 0.05).


CONCLUSIONS
NAC treatment had beneficial effects in sodium taurocholate-induced AP in rats. It reduced pancreatic tissue necrosis and lipid peroxidation. In our study, the mechanism underlying the beneficial effects of NAC seemed to be its antioxidant activity, either by increasing hepatic GPx activity, or by a direct scavenging effect on free radicals, thus enhancing the production of and/or inhibiting the degradation of nitric oxide.
Yagci
Gokhan
G
Department of General Surgery, Gulhane Military Medical Academy, Etlik, Ankara, Turkey.
Gul
Husamettin
H
Simsek
Abdurrahman
A
Buyukdogan
Varol
V
Onguru
Onder
O
Zeybek
Nazif
N
Aydin
Ahmet
A
Balkan
Mujdat
M
Yildiz
Oguzhan
O
Sen
Dervis
D
D000111:Acetylcysteine / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology*; D000208:Acute Disease; D000681:Amylases / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology*; D002756:Cholagogues and Choleretics; D005979:Glutathione Peroxidase / Q000378:metabolism; D008049:Lipase / Q000097:blood; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D010195:Pancreatitis / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D013656:Taurocholic Acid; D013997:Time Factors
D000975:Antioxidants; D002756:Cholagogues and Choleretics; D009566:Nitrates; D009573:Nitrites; D008315:Malondialdehyde; D013656:Taurocholic Acid; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D008049:Lipase; D000681:Amylases; D000111:Acetylcysteine