Effects of long term exposure to lipopolysaccharide on gastric injury and iNOS production

Abstract

Abstract Introduction: Short-term ( Methods: Rats were given saline or the highly selective iNOS inhibitor 1400W(1mg/kg IP) followed 15 minutes later by saline or LPS (20mg/kg IP). After 24 hrs, rats were sacrificed, gastric fluid aspirated, macroscopic injury (computerized planimetry) measured and mucosa harvested for iNOS assessment (Western blot) (N >4 group; ANOVA). Results: As shown in Table 1, LPS caused macroscopic gastric injury, increased iNOS, and increased accumulation of alkaline fluid within the gastric lumen compared to saline controls. 1400W inhibited LPS induced macroscopic gastric injury and prevented gastric luminal fluid alkalinization but had no effect on gastric luminal fluid accumulation. LPS induced upregulation of gastric iNOS production was not inhibited by 1400W. Table 1Effects of LPS with and without selective iNOS inhibition on the stomach.SalineLPS1400W/ saline1400W/ LPSGastric injury (mm 2 ) ± SE0.125 ± 0.77.85 ± 2.1∗0.25 ± 0.72.8 ± 0.7∗∗iNOS (densitometric units) ± SE0.24 ± 0.010.68 ± 0.09∗0.22 ± 0.020.67 ± 0.07∗Gastric pH ± SE2 ± 0.17.3 ± 0.3∗2 ± 0.12.9 ± 0.5∗∗Gastric volume (ml) ± SE0.25 ± 0.041.5 ± 0.3∗0.37 ± 0.040.9 ± 0.2∗p ≤ 0.05 vs saline (ANOVA).∗∗p ≤ 0.05 vs LPS (ANOVA). Conclusions: This is the first study to report macroscopic gastric injury occurs after LPS administration alone. Moreover, the effects of LPS on gastric mucosal integrity and iNOS production persist even after 24 hrs. These data further suggest that septic patients may be at risk for gastritis due to upregulation of iNOS.