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

Author(s)

Polli-Lopes, Ana Claudia ^[1] ; Estofolete, Cassia F. ^[1] ; Oliani, Sonia M. ^[2] ; Zucoloto, Sergio ^[3] ; Cunha, Fernando Q. ^[4] ; Gil, Cristiane D. ^[5]

Affiliation

^[1] Sao Jose do Rio Preto Sch Med FAMERP, Dept Anat, Sao Paulo - Brazil

^[2] Inst Biocincias Letras & Cincias Exatas IBILCE UN, Dept Biol, Sao Jose Do Rio Preto, SP - Brazil

^[3] Ribeirao Preto Sch Med FMRP USP, Dept Pathol, Ribeirao Preto, SP - Brazil

^[4] Ribeirao Preto Sch Med FMRP USP, Dept Pharmacol, Ribeirao Preto, SP - Brazil

^[5] Fed Univ Sao Paulo UNIFESP, Dept Morphol & Genet, BR-04023900 Sao Paulo - Brazil

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY; v. 6, n. 1, p. 13-23, 2013.
• Web of Science Citations: 6

Abstract

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 (similar to 29%) compared with the untreated MNNG group (similar to 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. (AU)

• FAPESP's process: 08/05722-6 - Study of galectin-3 and Annexin-A1 expression in the inflammatory cells during experimental model of gastric tumorigenesis in rats
• Grantee: Cássia Fernanda Estofolete
• Support Opportunities: Scholarships in Brazil - Scientific Initiation