Protective effect of pentoxifyllin on alcohol induced gastric mucosal damage in rats: Relation with prostoglandin and nitric oxide

Abstract

Pentoxifylline (PTX) has been shown to increase tissue oxygen tension and improve tissue oxygen delivery. Early microcirculatory stasis is a major factor in gastric mucosal injury induced by ethanol in rats, PTX a methyl xanthine derivate prevents microcirculatory stasis and protects tissue by reducing tumour necrosis factor (TNF-?). This study investigated whether ptx induced protection involves nitric oxide mediated pathways or endogenous prostaglandins (PGs') production. Fifty-eight Swiss-Albino rats were divided into six groups and 2 ml of ethanol 98% was administered orogastrically to induce gastric mucosal injury. The animals were killed 30 minutes after gastric injury by cervical dislocation. In all groups, gastric mucosal injury was evaluated/measured by macroscopic and microscopic methods and glutathion ratio (GSH/GSSG) and malondialdehyde (MDA) levels in gastric tissue. One hour prior to ethanol administration the following were also administered Group 1: serum physiologic (SF) intraperitoneally (ip) 1 ml, Group 2:100 mg/kg PTX ip, Group 3:100 mg/kg PTX ip one hour following 1 ml SF subcutan (sc), Group 4: 100 mg/kg PTX ip one hour following 5 mg/kg indomethacin sc, Group 5: 100 mg/kg PTX ip one hour following 1 ml SF ip, Group 6:100 mg/kg PTX ip one hour after 60 mg/kg L-NAME (Nitric oxide synthesis inhibitor) ip subcutaneously. Results: PTX pretreatment prior to ethanol administration significantly reduced macroscopic and microscopic scores of gastric mucosal injury (10.6 ± 3.7 mm versus 27.5 ± 19.5, 0.88 ± 0.60 versus 1.87 ± 0.83, p < 0.05) respectively. PTX pretreatment also reduced MDA levels in gastric tissue 351.1 ± 94.0 versus 624.3 ± 234 mmol/gwettissue, (p < 0.01) but did not effect GSH/GSSG ratio. The experimental results of inhibition of endogenous PGs' synthesis was not affected by indomethacin, but administration of L-NAME significantly increased the gastric mucosal injury. Conclusion: PTX prevents ethanol induced gastric mucosal injury in rats. This effect is not related to the synthesis of prostaglandins, but does seem to be related to nitric oxide mediated pathways.