Display Settings:


Send to:

Choose Destination
See comment in PubMed Commons below
Int J Clin Exp Pathol. 2013;6(1):13-23. Epub 2012 Nov 20.

Myenteric denervation in gastric carcinogenesis: differential modulation of nitric oxide and annexin-A1.

Author information

  • 1Department of Anatomy, São José do Rio Preto School of Medicine-FAMERP São Paulo, SP, Brazil.


This study evaluated the properties of endogenous nitric oxide synthases (NOS) and annexin-A1 (ANXA1) and determined how they can be exploited in the N-methyl-N-nitro-N-nitrosoguanidine (MNNG)-induced gastric carcinogenesis and myenteric denervation model. Male Wistar rats were treated with MNNG and/or aminoguanidine (AG) for 20 weeks. In another set of experiments, rats with nondenervated and denervated stomachs were treated with MNNG or water for 28 weeks. Fragments of the pyloric region were processed for histopathology, NOS activity, and immunohistochemistry to explore the activity and expression of constitutive (cNOS) and inducible (iNOS) NO synthase and their relationship with annexin-A1 (ANXA1) expression. NO inhibition by AG increased the percentage of animals with adenocarcinomas (~29%) compared with the untreated MNNG group (~4%). Myenteric denervation did not alter NOS activity. cNOS activity was significantly greater in nondernervated and denervated stomachs with or without lesions (P<0.001) than iNOS activity (P<0.01), as confirmed by immunohistochemistry. Further, cNOS activity in normal stomachs and outside the lesion area was considerably higher than inside it (P<0.01). By densitometric analysis of nondenervated and denervated stomachs, ANXA1 expression was modulated in epithelial and inflammatory cells (mast cells and neutrophils), wherein significant alterations were induced by lesion development and myenteric denervation. In conclusion, NO protects against the development of gastric adenocarcinomas. The pattern of ANXA1 expression was not associated with NOS activity or expression, suggesting that NO and ANXA1 act in gastric tumors in disparate pathways.


Benzalkonium chloride; N-methyl-N-nitro-N-nitrosoguanidine; immunohistochemistry; inflammation; lipocortin-1; nitric oxide synthase

[PubMed - indexed for MEDLINE]
Free PMC Article

Images from this publication.See all images (5)Free text

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for PubMed Central
    Loading ...
    Write to the Help Desk