The effects of antithrombin-III on inducible nitric oxide synthesis in experimental obstructive jaundice. An immunohistochemical study.
The absence of bile in the gastrointestinal tract stimulates bacterial overgrowth and bacterial translocation. In the response to endotoxin and LPS-induced endotoxemia which may be prevented by antithrombin-III (AT-III); endothelial cells; and various cells release cytokines, nitric oxide (NO) and other mediators. The purpose of this study was to examine blood NO levels and renal inducible NO synthase (iNOS) expression and determine whether AT-III has an inhibiting effect on renal injury and iNOS expression in obstructive jaundice (OJ). Forty rats were randomized into four groups: group A (Sham), group B (Sham+AT-III, 250 IU kg(-1)), group C (OJ), group D (OJ+AT-III, 250 IU kg(-1)). All animals were sacrificed on the 10th day and blood samples were taken for bilirubin and NO level determination. In addition, iNOS expression of the renal tissues was evaluated immunohistochemically. Blood NO levels were found to be 32.99 micromol l(-1) in group A, 32.26 micromol l(-1) in group B, 46.33 micromol l(-1) in group C, and 34.71 micromol l(-1) in group D. The intensity of iNOS staining in the OJ+AT-III group was less than the intensity of iNOS staining in the OJ group in the renal tissue. This study shows that OJ causes increased production of NO in blood and increased iNOS expression in the kidney. AT-III inhibits iNOS expression and reduces the level of blood NO. Thus, our findings indicate that under conditions of OJ, AT-III limits renal cellular injury by inhibiting LPS-induced iNOS expression.
D000818:Animals; D000990:Antithrombin III / Q000494:pharmacology*; D002779:Cholestasis / Q000201:enzymology* / Q000473:pathology; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects / Q000201:enzymology; D007684:Kidney Tubules / Q000201:enzymology / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000097:blood / Q000378:metabolism / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017208:Rats, Wistar; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*
D015842:Serine Proteinase Inhibitors; D009569:Nitric Oxide; D000990:Antithrombin III; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat