AI Summary & Key Takeaways
AI InsightThis effect is not related to the synthesis of prostaglandins, but does seem to be related to nitric oxide mediated pathways.
📌 3 Key Takeaways
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-a). 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 2ml 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 udministration 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±234mmol/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.
Özet
Bu çalışmada sıçanlarda alkolün oluşturduğu gastrik mukozal hasar modeli kullanılarak, pentoksifilinin (PTX) koruyucu rolü; prostaglandinler (PG), nitrik oksit (NO) ve serbest oksijen radikalleriyle olan ilişkisi incelenmiştir. Altı gruba ayrılan (n=8-10) sıçanlara 2 ml %98'lik alkol orogastrik yolla verilerek gastrik hasar oluşturulmuştur. Bundan 30 dak. sonra hayvanlar sakrifiye edilerek midelerinde gelişen mukozal hasar makroskopik ve mikroskopik olarak değerlendirilmiş, mide pH'sı ölçülmüş, ayrıca dokuda malondialdehid (MDA) ve okside ve redükte glutatyon (GSSG ve GSH) düzeyleri tayin edilmiştir. Gruplara alkolden 1 saat önce; Grup 1: serum fizyolojik (SF) intraperitoneal (i.p.) 1 ml, Grup 2: 100 mg/kg PTX i.p., Grup 3: 1 ml SF subcutan (s.c.) 1 saat sonra 100 mg/kg PTX i.p., Grup 4: 5mg/kg dozda indometazin s.c. 1 saat sonra 100 mg/kg PTX i.p., Grup 5: 1 ml SF 1 saat sonra 100 mg/kg PTX i.p., Grup 6: 60 mg/kg dozda L-NAME (NO sentez inhibitörü)1 saat sonra 100 mg/kg PTX i.p. uygulanmıştır. Alkolden önce PTX ile yapılan ön tedavi makroskopik ve mikroskopik lezyon skorunu anlamlı şekilde azaltmıştır (sırasıyla; 27.5±19.5'e karşı 10.6±3.7, p<0.05 ve 1.87±0.83'e karşı 0.88±0.60, p<0.05). PTX verilen grupta MDA düzeyi 351.1±94 nmol/g yaş doku iken kontrol grubunda 624.3±234 bulunmuştur (p=0.01), GSH/GSSG oranı ise benzer bulunmuştur. İndometazin verilerek PG sentezinin inhibe edilmesi deney sonuçlarını etkilemezken, L-NAME verilmesi gastrik mukozal hasarı belirgin şekilde artırmıştır. Sonuç olarak, sıçanlarda alkolle oluşturulan gastrik mukozal hasarda pentoksifilin koruyucu bir rol oynamakta ve bu etki PG'lerden bağımsız, NO ile ilişkili mekanizmalar üzerinden gerçekleşmektedir.