Enteral nutrition affects nitric oxide levels in both peripheral blood and liver tissue in an experimental model of postoperative sepsis

Background

Sepsis is a common postoperative complication, leading to the augmentation of the oxidative stress induced by the operation itself. Numerous studies have emphasized the role of nitric oxide (NO) in influencing hepatic function during sepsis.

Aim and methods

The present study was designed to investigate the role of enteral nutrition on the postoperative sepsis-induced NO production, as an index of oxidative stress. Five groups of 10 male Wistar rats were subjected to midline laparotomy and feeding gastrostomy. Ten rats were allowed to recover from operation stress for 10 days and served as controls. The remaining 40 rats were allocated to receive through gastrostomy either enteral feeding (Fresubin-HP Energy, Fresenius-Kabi, 2 ml/hour, 75 kcal/day) or water for 24 hours, after which they were subdivided into two other groups by intraperitoneal injection of 10 mg/kg Escherichia coli lipopolysacchardie (LPS) (Difco 0111:B4; Sigma Chemicals) or placebo. Two hours later all rats were sacrificed, having first been subjected to blood and liver tissue sampling. The NO production was quantified by measuring the total nitrite plus nitrate concentration in serum samples and in liver tissue homogenates, by means of a spectrophotometric method that uses a modification of the Griess reaction. NO synthase mRNA expression was examined in the homogenate of liver tissue in RNAzol by RT-PCR.

Results

A basal production of NO was found in the serum of control rats. The operation itself was found to induce a significant increase (P < 0.01) of NO levels in the serum and the injection of LPS further induced NO levels (P < 0.001). Enteral feeding was found to significantly decrease (P < 0.01) NO levels in both groups. In contrast, NO in liver homogenates was found significantly increased (P < 0.05) in enteral nutrition plus LPS-treated rats compared with placebo feeding plus LPS. Interestingly, LPS was found to induce inducible NO synthase (iNOS) mRNA expression in liver tissue, regardless of the enteral feeding, while liver from placebo (no LPS) treated animals did not express iNOS mRNA.

Conclusion

These findings indicate that early enteral feeding leads to a reduction of the circulating NO levels induced by operation and sepsis, but increases hepatic NO levels, probably via the effect of the LPS-induced iNOS on the increased L-arginine uptake.