Administration of L-arginine reduces the delay of the healing process caused by ibuprofen. Implication of COX and growth factors expression
S. Sánchez-Fidalgo1, I. Martín-Lacave2, M. Illanes2, L. Bruseghini3, A. Esteras3 and V. Motilva3
1Departament of Pharmacolgy, Faculty of Pharmacy, University of Seville, Spain, 2Department of Normal and Pathological Citology and Histology, Faculty of Medicine, University of Seville, Spain and 3Zambon Group, Sta. Perpetua de Mogoda, Barcelona, Spain
Offprint requests to: Dr Virginia Motilva, Departament of Pharmacology, Faculty of Pharmacy, University of Seville, 41012 Seville. Fax: + 34 954 233765 . e-mail: motilva@us.es
Summary. The objective of the present study has been to advance knowledge of the gastric role played by the amino acid L-Arginine (L-Arg) in the evolution of a chronic gastric ulcer. In order to clarify it, L-Arg alone or together with Ibuprofen have been administrated in an experimental acetic acid chronic ulcer, analysing characteristic parameters of an active curative process, such as PGE2 production, COX expression, and also angiogenesis, proliferation/apoptosis and growth factors expression. Our results reveal that L-Arg is favourable in the healing process improving the curative course. Ibuprofen caused a delay in ulcer healing, more evident 14 days after ulcer induction; COX-2 expression was increased at the 7th day although no signal of protein could be detected after 14 days; PGE2 production was inhibited in intact and ulcerated areas at both times assayed. In contrast, treatment with L-Arg reduced the delay of the lesion, the increment in COX-2 expression induced by Ibuprofen, and was able to maintain PGE2 levels similar to the control group after 14 days. Additionally, the histological study showed that the healing effects of L-Arg might be associated with an increased angiogenesis and FGF-2 expression. These actions could be considered key factors in the healing response associated with L-Arg administration. However, the proliferation study assayed with the PCNA-immunostaining method did not reveal significant differences, as the same as the apoptosis analysis. In conclusion, the coupling of L-Arg to Ibuprofen is an attractive alternative to Ibuprofen administration alone because it not only attenuates but also improves the evolution of chronic lesions through mechanisms that implicate endogenous PG and FGF-2-associated pathways, which allow an increase of angiogenesis process. Histol Histopathol 20, 437-447 (2005).
Key words: NSAID, L-Arginine, COX, FGF-2, angiogenesis, chronic gastric ulcer
DOI: 10.14670/HH-20.437