Effects of oral administration of (L)-arginine, (L)-NAME and allopurinol on intestinal ischemia/reperfusion injury in rats.

AIMS: Intestinal ischemia/reperfusion (I/R) injury is implicated in many clinical conditions, and it performs a fundamental role in their pathophysiologies. Oral administration of antioxidants and nitric oxide (NO) donors ameliorate intestinal injury. Here, the effects of l-arginine, allopurinol and N(G)-nitro-l-arginine methyl ester (l-NAME) were investigated. MAIN METHODS: One hundred twenty-eight male Wistar rats were separated into 4 groups and subjected to occlusion of the superior mesenteric artery for 60 min. The Control group did not receive any substance before the surgical operation. However, the 3 other groups received the following: l-arginine (800 mg/kg body weight; l-Arg group), l-NAME (50mg/kg; l-NAME group) or allopurinol (100mg/kg; Allo group). Each substance was given by mouth in 3 equal doses 24, 12 and 1h before the surgical operation. Each group was then divided into 4 subgroups, which underwent different durations of reperfusion (0, 1, 8 or 24h). At the end of each time point, blood and tissue samples were collected, and histological examinations were performed. Serum nitrite and catalase, intestinal tissue myeloperoxidase (MPO), inducible nitric oxide synthase (iNOS) and nitrotyrosine (NT) levels were determined. KEY FINDINGS: At each reperfusion time point, the Allo group exhibited the mildest histological lesions in contrast to the l-NAME group, which showed the most severe lesions. MPO was decreased significantly in the Allo and l-Arg groups during reperfusion, and allopurinol administration caused earlier and stronger effect. iNOS and NT levels were higher in the l-Arg group and lower in the Allo group. Serum nitrite and catalase were increased in the l-NAME group after 24h. SIGNIFICANCE: Oral administration of allopurinol exerted a strong and protective effect on the intestinal tissue that was subjected to I/R earlier than l-arginine. This finding was also supported with the MPO, iNOS and NT data.

Time-dependent alterations in serum NO concentration after oral administration of L-arginine, L-NAME, and allopurinol in intestinal ischemia/reperfusion.

OBJECTIVE: To study the effect of oral administration of a nitric oxide (NO) donor L-arginine (L-Arg), a NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) and an inhibitor of xanthine oxidase, allopurinol (Allo), on serum NO concentration and catalase activity after intestinal ischemia/reperfusion (I/R) in rats. METHODS: Male Wistar rats receivedper os L-Arg (800 mg/kg) or L-NAME (50 mg/kg) or Allo (100 mg/kg) 24 hrs, 12 hrs and 1 hr before underwent 1 hr occlusion of superior mesenteric artery followed by 1 hr of reperfusion (L-Arg(IR1), L-NAME(IR1) and Allo(IR1) respectively) or 1 hr occlusion followed by 8 hrs of reperfusion (L-Arg(IR8), L-NAME(IR8) and Allo(IR8) respectively). There was one group underwent 1 hr occlusion (I), a group underwent 1 hr occlusion followed by 1 hr reperfusion (IR1), a group subjected to 1 hr occlusion followed by 8 hrs of reperfusion (IR8) and a last group that served as control (C). Serum NO concentration and catalase activity were measured. RESULTS: After 1 hr of reperfusion serum NO concentration was elevated in IR1 and L-Arg(IR1) groups compared with group C but not in L-NAME(IR1) and Allo(IR1) group. Catalase activity was enhanced in L-NAME(IR1) group. Interestingly, serum NO concentration was increased after 8 hrs of reperfusion in all groups (IR8, L-Arg(IR8), L-NAME(IR8) and Allo(IR8)) compared with control while catalase activity did not show significant difference in any group. CONCLUSIONS: The results of the present study show that NO concentration is elevated in serum after intestinal I/R and the elevation sustained after administration of L-Arg but not after administration of L-NAME or Allo after 1 hr reperfusion. However, after 8 hrs of reperfusion NO concentration was increased in all groups studied, focusing attention on its possible important role in a complicated situation such as intestinal I/R that involves intestine and other organs. Serum catalase activity does not seem to be affected by per os supplementation of L-Arg or Allo in intestinal I/R.