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Role of inducible nitric oxide synthase in dextran sulphate sodium-induced colitis
1The Second Department of Internal Medicine, National Defense Medical College, School of Medicine, Tokorozawa, Saitama, Japan.
Background:
Different authors have postulated both toxic and protective effects for nitric oxide (NO) in the pathophysiology of active inflammation.
Aim:
To examine the role of NO, especially that produced by the inducible form of nitric oxide synthase (iNOS), by investigating the effects of NOS inhibitors and NO donors on inflammation in experimental acute colitis.
Methods:
Acute colitis was induced in rats by dextran sulphate sodium (DSS). White blood cell counts and levels of thiobarbituric acid reactants in the portal blood were determined, as were histological changes in the colonic mucosa. We then evaluated the effects of N(G)-nitro-L-arginine methyl ester (L-NAME), aminoguanidine (AG) and an NO donor on DSS-induced changes in these inflammatory parameters.
Results And Conclusions:
Inhibition of NO production by either L-NAME or AG worsened DSS-induced inflammation, suggesting a protective role for NO in acute colitis. On the other hand, a NO donor also exaggerated DSS-induced inflammatory parameters, suggesting that acute colitis may be aggravated by either too much or too little NO. These results suggest that medical treatment of ulcerative colitis must aim for maintenance of appropriate NO levels in the intestinal mucosa.
Insights
Nitric oxide (NO) plays a dual role in acute colitis. Inhibiting NO worsened inflammation, but excessive NO donors also aggravated symptoms, indicating a need for balanced NO levels in ulcerative colitis treatment.
Area of Science:
- Gastroenterology
- Immunology
- Pharmacology
Background:
- Nitric oxide (NO) has been implicated in active inflammation, with conflicting reports on its toxic and protective roles.
- The specific contribution of inducible nitric oxide synthase (iNOS)-derived NO in inflammatory conditions remains unclear.
Purpose of the Study:
- To investigate the role of NO, particularly iNOS-derived NO, in experimental acute colitis.
- To evaluate the effects of nitric oxide synthase (NOS) inhibitors and NO donors on inflammation.
Main Methods:
- Acute colitis was induced in rats using dextran sulphate sodium (DSS).
- Inflammatory markers assessed included white blood cell counts, thiobarbituric acid reactants in portal blood, and colonic mucosal histology.
- The effects of N(G)-nitro-L-arginine methyl ester (L-NAME), aminoguanidine (AG), and an NO donor were examined.
Main Results:
- Inhibition of NO production using L-NAME or AG exacerbated DSS-induced colitis.
- Administration of an NO donor also worsened inflammatory parameters in DSS-induced colitis.
Conclusions:
- NO appears to have a protective role in acute colitis, as its inhibition worsened the condition.
- Both insufficient and excessive NO levels can aggravate acute colitis, suggesting a critical balance is required.
- Therapeutic strategies for ulcerative colitis should focus on maintaining optimal NO levels within the intestinal mucosa.