Intestinal ischemia and reperfusion injury in growing rats: Hypothermia and N‐acetylcysteine modulation

Abstract

Our objective was to evaluate intestinal ischemia-reperfusion injury in growing rats, modulated by hypothermia (I/RH) and N-acetylcysteine (NAC). We used 30 EPM-1 Wistar male rats, aged around 35 days, weighing 90 g. Rats were randomized into 5 groups with 6 animals in each: I/RH group, intestinal ischemia under hypothermia for 40 min and reperfusion for 30 min; I/RH-NAC group, same procedure but adding NAC (150 mg x kg(-1)), previously with ischemia; S-H group, topic hypothermia for 40 min, and observation for 30 min; I/R H-Ve group; and S-NAC group, NAC administration and observation for 70 min. All animals were heparinized and anesthetized with ketamine (60 mg kg(-1)) and xylazine (10 mg kg(-1)) intramuscularly. Surgical procedures were done under microsurgical technique (augmentation, 10x). After laparotomy, the superior mesenteric artery was dissected and clamped to promote ischemia. Topic hypothermia was obtained by using plastic bags at 4 degrees C, changed every 10 min. Rats were sacrificed by exsanguination, and blood samples were utilized to measure D(-)lactate. Intestinal fragments were removed for morphological study. Statistical analysis was done with nonparametric tests (P <or= 0.05). Concerning to D(-)lactate, the data showed biochemical tissue injury, with hypothermia only (S-H = 27 mg/dl), and this became more important when intestinal ischemia and reperfusion were associated to hypothermia (I/RH = 36 mg/dl). NAC decreased ischemia-reperfusion injury (I/RH-NAC = 19 mg/dl). Morphologic tissue injuries, evaluated by hematoxylin-eosin staining, showed grades 4 and 5 for the I/RH and I/RH-Ve groups, respectively, in contrast with other groups (I/RH-NAC = 2, S-H = 1, and S-NAC = 1). Based on our data, we conclude that intestinal ischemia reperfusion injury occurred morphologically as well as functionally, even under hypothermia. However, NAC showed a protective effect on the small bowel from ischemia-reperfusion injury.

Effect of N-Acetylcysteine Pretreatment of Deceased Organ Donors on Renal Allograft Function

“…Experimental studies have shown that NAC improves ischemia-reperfusion injuries in various organs, such as the liver 42 and the bowels. 43 The impact of NAC has been widely evaluated during various renal ischemia-reperfusion conditions including CI-AKI and renal transplantation. 7 , 22 , 28 , 29 , 36 The improvement of kidney injuries seems to result from several mechanisms associating decreased oxidative stress, nitric oxide-inhibiting effect leading to vasodilation, and preventive decrease in cytokine production and in apoptotic cell death.…”

Hypothermia as a Treatment for Birth Asphyxia

“…These include brain cooling, allopurinol, magnesium, minocycline, erythropoietin, insulinlike growth factor, MK-801, BAF (boc-aspartyl [OMe]-fluoromethylketone), topiramate, N-acetyl cysteine, and stem cells. 2,[19][20][21][22][23][24] Each of these therapies addresses one or more mechanisms involved in the multiple pathways contributing to brain injury as cited above. Of all of these potential therapies, brain cooling has the most experimental support.…”

Histological analysis of the intestinal wall of newborn rats submitted to hypoxia and reoxygenation to evaluate the protective effect of N-Acetylcysteine

“…In some experimental studies of ischemia and reperfusion 11,12,15 , the histopathological references used to measure protection were the classification of intestinal injury according to Chiu et al 25 and Ozdemir et al 23 , who used their own classification as parameters for histological evaluation. Montero et al 15 used the score proposed by Park et al 26 In the present study, we defined using the width and height of the intestinal villi obtained as parameters for the histological evaluation of the different groups.…”

“…formation of free radicals in various organs, especially in phenomena involving oxidative stress [13][14][15][16] .…”