L-arginine administration ameliorates serum and pulmonary cytokine response after gut ischemia-reperfusion in immature rats

Abstract

Small intestinal ischemia-reperfusion (IR) has been demonstrated to result in both local mucosal injury and systemic injuries. The exact role of nitric oxide (NO) in intestinal IR is unclear. We propose that NO and some other cytokines change in the reperfusion period and these changes are associated with lung injury. The aim of this study was to determine the effect of supplementing NO substrate, L-arginine (L-arg), on serum and pulmonary cytokine production during small intestinal IR in immature rats. Immature rats underwent 60 min. of superior mesenteric artery occlusion followed by 90 min of reperfusion. L-arg (250 mg/kg) was given intravenously to the experimental group (IR+L-arg) which received L-arg after 45 min of intestinal ischemia. Serum and lung endothelin-1 (ET-1), NO, malondialdehyde (MDA), and tumor necrosis factor alpha (TNFalpha) were measured. Sham operation (SHAM) and intestinal IR (IR) groups were performed as control. The lavage fluid of the lung was collected by bronchoalveolar lavage (BAL) and white blood cells and polymorphonuclear cells (PMNs) were immediately counted to identify lung damage. When L-arg was given during small intestinal IR, serum NO concentration increased significantly in IR+L-arg group (162.17+/-42.93 micromol/L) when compared with IR group (87.57+/-23.17 micromol/L, t = 3.190, P = 0.008<0.01). Serum MDA reduced significantly in IR+L-arg group (8.93+/-1.50 nmol/L) when compared with SHAM (23.78+/-7.81 nmol/L, t = 3.243, P = 0.007<0.01) and IR (25.54+/-9.32 nmol/L, t = 3.421, P = 0.006<0.01). ET-1 level in lung tissues was significantly lower in IR+L-arg group (13.81+/-7.84 pg/mL) than that in SHAM (35.52+/-10.82 pg/mL, t = 2.571, P = 0.03<0.05) and IR (50.83+/-22.05 pg/mL, t = 3.025, P = 0.009<0.01) groups. MDA contents in lung tissues were significantly lower in IR+L-arg group (10.73+/-1.99 nmol/L) than in SHAM (16.62+/-2.28 nmol/L, t = 3.280, P = 0.007<0.01) and IR (21.90+/-4.82 nmol/L, t = 3.322, P = 0.007<0.01) groups. Serum and lung TNFalpha concentrations were not significantly different in three groups. NO contents in lung homogenates and white blood cell counts in BAL had no significant difference in three groups; but the percentage of PMNs in BAL was 13.50+/-8.92, 33.20+/-16.59, and 22.50+/-6.09 in SHAM, IR, and IR+L-arg groups, respectively. Small intestinal IR induced increases of pulmonary neutrophil infiltration in immature rats. Neutrophil infiltration in lung tissues was reduced by L-arg administration but remained higher than in SHAM group. L-arg administration during intestinal IR enhances serum NO production, reduces serum MDA and lung ET-1 and MDA levels, resulting in the improvement of systemic endothelial function. L-arg supplementation before reperfusion may act as a useful clinical adjunct in the management of intestinal IR, thus preventing the development of adult respiratory distress syndrome, even multiple organ dysfunction syndrome (MODS).