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Gastroprotection by pentoxyfilline against stress-induced gastric damage. Role of lipid peroxidation, antioxidizing enzymes and proinflammatory cytokines.
J Physiol Pharmacol. 2004 Jun; 55(2):337-55.JP

Abstract

Impairment of blood perfusion in gastric mucosa results in the formation of erosions and ulcers. Nitric oxide (NO), produced via activity of NO-synthase (NOS), appears to be a one of major factors, involved in the regulation of the gastric blood flow (GBF). Inhibition of this enzyme by N-nitro-L-arginine (L-NNA) results in local decrease of NO production, reduces GBF and impairs gastric mucosal integrity, the effects that can be reversed by the pretreatment with L-arginine, the NOS substrate. However, little information is available regarding the contribution of reactive oxygen species (ROS)-induced lipid peroxidation and NO to the mechanism of gastric mucosal integrity. Therefore, the aim of our present study was to determine the action of pentoxyfilline (PTX), an inhibitor of tumor necrosis factor alpha (TNFalpha) with or without NOS inhibition by L-NNA administration in rats with water immersion and restraint stress (WRS)-induced gastric lesions. Experiments were carried out on 100 male Wistar rats. The gastric blood flow (GBF) was measured using laser Doppler flowmeter. The area of gastric lesions was determined by planimetry and the levels of proinflammatory cytokines (IL-1beta and TNFalpha) were measured by ELISA. Colorimetric assays were employed to determine gastric mucosal levels of lipid peroxidation products, such as malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) and antioxidant enzymes including superoxide dismutase (SOD) activity, as well as tissue concentration of reduced glutathione (GSH). Administration of PTX significantly attenuated the gastric lesions, induced by 3.5 h of WRS and this was accompanied by the rise in the GBF and a significant decrease in plasma proinflammatory cytokines (IL-1beta and TNFalpha) levels, as well as the reduction of lipid peroxidation. Exposure of rats to WRS suppressed the SOD and GSH activities and these effects were reversed by PTX. The protective and hyperemic effects of PTX, as well as an increase in mucosal SOD activity and GSH concentration were counteracted by pretreatment with L-NNA, but restored by the pretreatment with L-arginine, a NOS substrate. We conclude that PTX exerts beneficial, gastroprotective effect against WRS-induced gastric lesions due to enhancement in gastric microcirculation, possibly mediated by the enhanced NOS activity as well as local action of NO and by the attenuation of oxidative metabolism and generation proinflammatory cytokines.

Authors+Show Affiliations

Department of Physiology Jagiellonian University School of Medicine, Cracow, Poland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15213357

Citation

Kwiecień, S, et al. "Gastroprotection By Pentoxyfilline Against Stress-induced Gastric Damage. Role of Lipid Peroxidation, Antioxidizing Enzymes and Proinflammatory Cytokines." Journal of Physiology and Pharmacology : an Official Journal of the Polish Physiological Society, vol. 55, no. 2, 2004, pp. 337-55.
Kwiecień S, Brzozowski T, Konturek PC, et al. Gastroprotection by pentoxyfilline against stress-induced gastric damage. Role of lipid peroxidation, antioxidizing enzymes and proinflammatory cytokines. J Physiol Pharmacol. 2004;55(2):337-55.
Kwiecień, S., Brzozowski, T., Konturek, P. C., Pawlik, M. W., Pawlik, W. W., Kwiecień, N., & Konturek, S. J. (2004). Gastroprotection by pentoxyfilline against stress-induced gastric damage. Role of lipid peroxidation, antioxidizing enzymes and proinflammatory cytokines. Journal of Physiology and Pharmacology : an Official Journal of the Polish Physiological Society, 55(2), 337-55.
Kwiecień S, et al. Gastroprotection By Pentoxyfilline Against Stress-induced Gastric Damage. Role of Lipid Peroxidation, Antioxidizing Enzymes and Proinflammatory Cytokines. J Physiol Pharmacol. 2004;55(2):337-55. PubMed PMID: 15213357.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Gastroprotection by pentoxyfilline against stress-induced gastric damage. Role of lipid peroxidation, antioxidizing enzymes and proinflammatory cytokines. AU - Kwiecień,S, AU - Brzozowski,T, AU - Konturek,P C, AU - Pawlik,M W, AU - Pawlik,W W, AU - Kwiecień,N, AU - Konturek,S J, PY - 2004/03/02/received PY - 2004/05/07/accepted PY - 2004/6/24/pubmed PY - 2004/12/23/medline PY - 2004/6/24/entrez SP - 337 EP - 55 JF - Journal of physiology and pharmacology : an official journal of the Polish Physiological Society JO - J Physiol Pharmacol VL - 55 IS - 2 N2 - Impairment of blood perfusion in gastric mucosa results in the formation of erosions and ulcers. Nitric oxide (NO), produced via activity of NO-synthase (NOS), appears to be a one of major factors, involved in the regulation of the gastric blood flow (GBF). Inhibition of this enzyme by N-nitro-L-arginine (L-NNA) results in local decrease of NO production, reduces GBF and impairs gastric mucosal integrity, the effects that can be reversed by the pretreatment with L-arginine, the NOS substrate. However, little information is available regarding the contribution of reactive oxygen species (ROS)-induced lipid peroxidation and NO to the mechanism of gastric mucosal integrity. Therefore, the aim of our present study was to determine the action of pentoxyfilline (PTX), an inhibitor of tumor necrosis factor alpha (TNFalpha) with or without NOS inhibition by L-NNA administration in rats with water immersion and restraint stress (WRS)-induced gastric lesions. Experiments were carried out on 100 male Wistar rats. The gastric blood flow (GBF) was measured using laser Doppler flowmeter. The area of gastric lesions was determined by planimetry and the levels of proinflammatory cytokines (IL-1beta and TNFalpha) were measured by ELISA. Colorimetric assays were employed to determine gastric mucosal levels of lipid peroxidation products, such as malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) and antioxidant enzymes including superoxide dismutase (SOD) activity, as well as tissue concentration of reduced glutathione (GSH). Administration of PTX significantly attenuated the gastric lesions, induced by 3.5 h of WRS and this was accompanied by the rise in the GBF and a significant decrease in plasma proinflammatory cytokines (IL-1beta and TNFalpha) levels, as well as the reduction of lipid peroxidation. Exposure of rats to WRS suppressed the SOD and GSH activities and these effects were reversed by PTX. The protective and hyperemic effects of PTX, as well as an increase in mucosal SOD activity and GSH concentration were counteracted by pretreatment with L-NNA, but restored by the pretreatment with L-arginine, a NOS substrate. We conclude that PTX exerts beneficial, gastroprotective effect against WRS-induced gastric lesions due to enhancement in gastric microcirculation, possibly mediated by the enhanced NOS activity as well as local action of NO and by the attenuation of oxidative metabolism and generation proinflammatory cytokines. SN - 0867-5910 UR - https://www.unboundmedicine.com/medline/citation/15213357/Gastroprotection_by_pentoxyfilline_against_stress_induced_gastric_damage__Role_of_lipid_peroxidation_antioxidizing_enzymes_and_proinflammatory_cytokines_ L2 - http://www.jpp.krakow.pl/journal/archive/06_04/pdf/337_06_04_article.pdf DB - PRIME DP - Unbound Medicine ER -