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Induction of nitric oxide synthase and concomitant suppression of superoxide dismutases in experimental colitis in
H G Seo1, I Takata, M Nakamura
1Department of Biochemistry, Osaka University School of Medicine, Japan.
Abstract:
Reactive oxygen species are thought to play an important role in some bowel diseases. In order to evaluate the participation of nitric oxide and superoxide in such diseases, we examined the expression of nitric oxide synthase (NOS) and superoxide dismutase (SOD) as well as their activities in whole excised colons of rats with colitis induced by intralumenal administration of 2,4,6-trinitrobenzenesulfonic acid. A marked increase in the inducible form of NOS mRNA was detected and NOS activity was coincidentally augmented in the group administered unbuffered TNBS (pH 1.0), in which severe inflammation was revealed by microscopic examination and myeloperoxidase activity of invading neutrophils in the tissues. The levels of the Mn- and Cu,Zn-SOD proteins as well as SOD activity were suppressed, although expression of the Mn-SOD mRNA was enhanced in colitis tissues. The elevation of NOS activity and the suppression of SOD activity occurred concomitantly at the stage of severe inflammation. This would increase peroxynitrite formation from superoxide and nitric oxide and enhance the tissue damage in experimental colitis.
Insights
Reactive oxygen species contribute to bowel diseases. This study found increased nitric oxide synthase (NOS) and decreased superoxide dismutase (SOD) activity in experimental colitis, suggesting a role in tissue damage.
Area of Science:
- Gastroenterology
- Biochemistry
- Pathology
Background:
- Reactive oxygen species (ROS) are implicated in the pathogenesis of inflammatory bowel diseases.
- Nitric oxide (NO) and superoxide (O2-) are key ROS that can interact to form peroxynitrite, a potent oxidant.
Purpose of the Study:
- To investigate the roles of nitric oxide synthase (NOS) and superoxide dismutase (SOD) in experimental colitis.
- To correlate the expression and activity of NOS and SOD with the severity of inflammation.
Main Methods:
- Induction of colitis in rats using 2,4,6-trinitrobenzenesulfonic acid (TNBS).
- Assessment of NOS and SOD expression (mRNA and protein) and enzyme activity in colon tissues.
- Microscopic examination and myeloperoxidase activity assay to quantify inflammation and neutrophil infiltration.
Main Results:
- TNBS-induced colitis showed a significant increase in inducible NOS mRNA and NOS activity, correlating with severe inflammation.
- Levels of Mn-SOD and Cu,Zn-SOD proteins and their activities were suppressed in colitis tissues.
- Mn-SOD mRNA expression was enhanced, despite reduced protein levels and activity.
Conclusions:
- Elevated NOS activity and suppressed SOD activity occur during severe experimental colitis.
- This imbalance likely promotes peroxynitrite formation, contributing to enhanced tissue damage in colitis.