Effects of the nitric oxide donor molsidomine on the early stages of liver damage in rats with bile duct ligation: a biochemical and immunohistochemical approach.
This study aimed to evaluate the effects of the nitric oxide donor molsidomine on the early stages of liver damage and biochemical changes in rats with bile duct ligation (BDL). Forty prepubertal male Sprague-Dawley rats weighing 125-140 g were studied. Group 1 rats (sham-control, n = 10) were not subjected to any surgical manipulation. Group 2 rats (BDL/untreated, n = 10) were subjected to BDL but no drug was administered. Group 3 rats (BDL/L-NAME, n = 10) received a daily dose of N(G)-nitro-L-arginine methyl ester (L-NAME) intraperitoneally for 7 days after BDL. Group 4 rats (BDL/molsidomine, n = 10) received a daily dose of molsidomine by gastric tube for 7 days after BDL. After 1 week, biochemical and histological evaluations were performed and the liver hydroxyproline content was measured. Serum bilirubin and liver enzymes were significantly increased in the BDL/untreated, BDL/L-NAME and BDL/molsidomine groups in comparison with the sham-control group 1 week after BDL. However, the liver enzymes were significantly decreased in the BDL/molsidomine group in comparison with the BDL/untreated and BDL/L-NAME groups. In the BDL/L-NAME group, proliferation of portal and periportal biliary ductules with disorganization of the hepatocyte plates, dilated portal spaces and areas of polymorphonuclear leukocyte infiltration, fibrosis and hepatocyte necrosis were observed. In the BDL/molsidomine group, polymorphonuclear leukocyte infiltration, hepatocyte necrosis and fibrosis were rarely seen. The hydroxyproline content in the liver was increased 1 week after obstruction in the BDL/untreated and BDL/L-NAME groups when compared to BDL/molsidomine group. Collagen type-IV expression was not observed in the BDL/molsidomine group in contrast to the BDL/untreated and BDL/L-NAME groups. In conclusion, during 1 week of treatment, the nitric oxide donor molsidomine improved hepatic fibrosis in the hepatic parenchyma and did not affect serum bilirubin values, but positively affected the serum aspartate aminotransferase and alanine aminotransferase values.
Oztürk
H
H
Department of Pediatric Surgery, Dicle University Medical School, Diyarbakir, Turkey. ozturkhayrettin@hotmail.com
Yağmur
Y
Y
Buyukbayram
H
H
Dokucu
A I
AI
Gurel
A
A
D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002779:Cholestasis / Q000188:drug therapy* / Q000473:pathology; D003094:Collagen / Q000032:analysis; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006909:Hydroxyproline / Q000032:analysis; D007150:Immunohistochemistry; D008026:Ligation; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008981:Molsidomine / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009336:Necrosis; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D005723:gamma-Glutamyltransferase / Q000097:blood
D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D003094:Collagen; D008981:Molsidomine; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D006909:Hydroxyproline; D019331:NG-Nitroarginine Methyl Ester