Intestinal Mucosal Injury Scores Research Articles

Lactobacillus complex capsules ameliorate aspirin-related small intestinal mucosal injury: a prospective, randomized, controlled clinical trial

Objectives Aspirin can reduce cardiovascular disease risk; however, it can increase the risk of gastrointestinal injury. Lactobacilli have some protective effects; however, there are few studies on their effects on humans. This study investigates the effects of Lactobacillus complex capsule treatment on the aspirin-related small intestinal mucosal injury. Methods This single-center, prospective, randomized controlled clinical trial included 69 patients using enteric-coated aspirin for >1 month between May and December 2019. After baseline magnetically controlled capsule endoscopy (MCCE), patients with aspirin-related small intestinal mucosal injury were randomly assigned (1:1) to receive enteric-coated aspirin and Lactobacillus complex capsules containing a combination of Lactobacillus rhamnosus I, Lactobacillus rhamnosus II, and Enterococcus faecium (probiotics group) or enteric-coated aspirin only (control group) for 2 months. After treatment, the patient underwent MCCE again. The primary outcome was the change in small intestinal mucosal injury scores from baseline to post-intervention. Results Twenty-five patients in the probiotics group and 28 in the control group completed the trial. The decrease in small intestinal mucosal injury scores from baseline to post-intervention was significantly greater in the probiotics group than that in the control group (p < .001). The improvement rates of red spots and erosions in the probiotics group were higher compared with the control group (p = .027 and .022, respectively), and the improvement rate of small intestinal ulcers in the probiotics group was 75.0%; however, there was no improvement in the control group. Conclusion Lactobacillus complex capsules can ameliorate aspirin-related small intestinal mucosal injury.

Histone deacetylase inhibitor attenuates intestinal mucosal injury in fatally scalded rats.

BackgroundSevere burns, trauma and shock can cause intestinal epithelial barrier dysfunction, which can lead to intestinal endotoxemia and even sepsis and multi-organ dysfunction. Many studies have shown that histone deacetylase inhibitors (HDACIs) can improve cell tolerance to hypoxia and inflammation, thus protecting the functions of important organs in the body, and at the same time, inhibiting the degradation of tight junction (TJ) proteins, protecting the intercellular barrier, and reducing tissue edema and organ damage. However, the mechanism is unclear.MethodsEighty male Sprague-Dawley rats (weighing 280–300 g) with a 50% total body surface area full-thickness dermal burn were randomly assigned to 4 groups (20 rats/group): sham control (SC group), scald + normal saline (SN group), scald + 2-methyl-2pentenoic acid (2M2P group), and scald + valproic acid (VPA group). After scalding, we measured the following parameters at various time intervals postburn injury: intestinal mucosal injury score, diamine oxidase (DAO) activity, intestinal protein expression of acetyl histone H3 at K9 (Ac-H3K9), hypoxia inducible factor 1α (HIF-1α), erythropoietin (EPO), zonula occludens-1 (ZO-1), endothelial nitric oxide synthase (eNOS) content, nitric oxide (NO) content, and intestinal mucosal blood flow (IMBF).ResultsIntestinal mucosa showed significant morphologic injury at 4 and 8 hours after scalding that was attenuated by VPA. DAO activity in the VPA group was significantly decreased compared with the other scald groups. At 4 and 8 hours after scalding, VPA enhanced Ac-H3K9 and ZO-1 expression and decreased HIF-1α and EPO expression in the intestine compared with the other scald groups. At 4 and 8 hours after scalding, eNOS and NO protein content and IMBF in the VPA group were markedly increased compared with the other scald groups.ConclusionsHDACIs attenuated intestinal mucosal injury in fatally scalded rats. This may have involved VPA enhancing Ac-H3K9 and ZO-1 expression, inhibiting HIF-1α and EPO expression and inducing eNOS and NO increments.

Hyperbaric Oxygen Treatment Improves Intestinal Barrier Function After Spinal Cord Injury in Rats

Intestinal barrier dysfunction is often observed clinically after spinal cord injury (SCI) and seriously affects long-term quality of life. Hyperbaric oxygen (HBO) treatment has been proved to promote barrier function recovery after injury, but the influence of HBO on intestinal barrier function following SCI is unclear. We aimed to investigate the effect and mechanisms of HBO treatment on intestinal barrier function by measuring the level of tight junction (TJ) proteins and the Ras homolog (Rho)/Rho-associated coiled-coil forming protein kinase (ROCK) signaling pathway. SCI model was established in rats, and the animals were randomly assigned into three groups: sham-operation group (SH), SCI group and SCI+HBO group. In the SCI+HBO group, the rats inhaled 100% O2 for 1 h at 2.0 atmospheres absolute pressure (ATA) once per day after surgery. Neurological function and intestinal permeability were assessed after surgery, and the jejunum tissue was excised for histological and intestinal barrier function evaluations. The protein levels of TJ and the Rho/ROCK signaling pathway were also measured. The results showed that in the SCI group, intestinal mucosal injury score, intestinal permeability, and levels of Rho and ROCK1 were higher, and TJ proteins occludin and ZO-1 were lower than those in the SH group (P < 0.01). HBO treatment significantly inhibited the expression of Rho and ROCK1, increased occludin and ZO-1 expression, decreased intestinal permeability, and alleviated intestinal mucosal injury as compared with the SCI group (P < 0.05, P < 0.01). The SCI+HBO group showed higher Basso–Beattie–Bresnahan (BBB) scores relative to the SCI group on postoperative days 7 and 14 (P < 0.01). There was a significant negative correlation between BBB score and intestinal mucosal injury score in rats after HBO treatment (P < 0.05). We concluded from this study that HBO treatment promoted the expression of TJ proteins possibly through inhibiting Rho/ROCK signaling pathway, which protected the intestinal barrier function and improved the intestinal permeability after SCI in rats.

Bioartificial liver attenuates intestinal mucosa injury and gut barrier dysfunction after major hepatectomy: Study in a porcine model

The aim of this study was to evaluate whether bioartificial liver support can attenuate gut mucosa injury in a porcine model of posthepatectomy liver dysfunction. Posthepatectomy liver failure was induced in pigs combining major (70%) liver resection and ischemia/reperfusion injury. An ischemic period of 150minutes was followed by reperfusion for 24hours. Animals were divided randomly into 2 groups: a control group (n=6) that received standard critical care and a bioartificial liver support group (Hepat, n=6) that were subjected to extracorporeal liver support for 6 hours during reperfusion. Intestinal mucosal injury, bacterial translocation, and endotoxin translocation were evaluated in all animals. Intestinal mucosa was also evaluated with markers of oxidative injury and immunohistochemical staining for caspase3. When compared with median values, the control group, animals in the Hepat group had a lesser intestinal mucosal injury score (4.0 [range:2.0-5.0] vs 1.0 [range:1.0-2.0]; P<.01), decreased bacterial translocation in the portal and the systemic circulation at 24hours of reperfusion (P<.05), and decreased portal and systemic endotoxin levels at 24hours (P<.05). At 24hours after reperfusion, mucosal protein carbonyls and malondialdehyde levels were decreased in Hepat animals (0.57nmol/mg [range:0.32-0.70] vs 0.33nmol/mg [range:0.03-0.53] and 3.85nmol/mg [range:3.01-6.43] vs 3.27nmol/mg [range:1.46-3.55], respectively; P<.05). There was no difference in tissue caspase staining. Bioartificial liver support seems to attenuate intestinal mucosal injury and gut barrier dysfunction after major hepatectomy.

Early prediction of intestinal mucosal barrier function impairment by elevated serum procalcitonin in rats with severe acute pancreatitis.

The aim of this study was to evaluate serum procalcitonin (PCT) levels as a prognostic indicator of intestinal barrier function impairment in rats with severe acute pancreatitis (SAP). Thirty-six male Sprague Dawley rats were randomly grouped into SAP group (injected sodium taurocholate via biliopancreatic duct), Gln group (gavaged with glutamine after modeling), and control group. Blood, pancreatic, and terminal ileum tissues were obtained from the rats after 6hof modeling. Serum amylase (Amy) levels were determined using an automatic biochemical detector, while endotoxin (ET), diamine oxidase (DAO), and PCT levels were measured by ELISA test. The pathology of pancreatic and small intestine tissues were observed. PCT protein expression in intestinal tissues were detected by immunohistochemistry and western blot. Pancreatic and intestinal injuries in Gln group were significantly lower than SAP group. Serum amylase, DAO, and PCT levels in SAP and Gln groups differed greatly and were significantly higher than control group. Immuno-histochemistry and western blot results showed that PCT protein expression levels in small intestine tissues of SAP group were higher than Gln group and control group. Serum PCT levels had a significant correlation with serum endotoxin, DAO levels and intestinal mucosal injury scores. PCT expression in serum and intestinal tissues in SAP rats increased significantly in the early stages of SAP, and was closely related to the onset and degree of intestinal barrier function impairment. Thus, our results showed that measuring serum PCT can be used to predict intestinal mucosal barrier function impairment in SAP rats.

Pyruvate Is Superior to Citrate in Oral Rehydration Solution in the Protection of Intestine via Hypoxia-Inducible Factor-1 Activation in Rats With Burn Injury.

Recent studies have suggested that pyruvate-enriched oral rehydration solution (Pyr-ORS) may be superior to the standard bicarbonate-based ORS in the protection of intestine from ischemic injury. The aim of this study was to compare the effects of Pyr-ORS with citrate-enriched ORS (Cit-ORS) on the intestinal hypoxia-inducible factor-1 (HIF-1)-erythropoietin (EPO) signaling pathway for enteral rehydration in a rat model of burn injury. Rats were randomly assigned to 4 groups (N = 20, 2 subgroups each: n = 10): scald sham (group SS), scald with no fluid resuscitation (group SN), scald and resuscitation with enteral Cit-ORS (group SC), and scald and resuscitation with enteral Pyr-ORS (group SP). At 2.5 and 4.5 hours after a 35% total body surface area (TBSA) scald, intestinal mucosal blood flow (IMBF), contents of HIF-1, EPO, endothelial nitric oxide synthase (eNOS), nitric oxide (NO), barrier protein (ZO-1), levels of serum diamine oxidase (DAO), and intestinal mucosal histology injury score were determined. Serum DAO activities in the scalded groups were significantly elevated, but less raised in group SP than in group SC, at 2.5 hours and at 4.5 hours after the scald. Further, group SP more profoundly preserved intestinal HIF-1 expression compared with group SC at the 2 time points. Compared with group SC, group SP had markedly elevated intestinal EPO, eNOS, and NO levels at the same time points, respectively (P < .05). Similarly, IMBF and ZO-1 levels were significantly higher in group SP than in group SC. Intestinal mucosal histopathological scores were statistically higher at 2.5 hours and 4.5 hours after scalding but were more attenuated in group SP than in group SC (P < .05). Immunofluorescence expression of intestinal mucosal ZO-1 was consistent with the above changes. The above parameters were also significantly different between groups SC and SN (all P < .05). Pyr-ORS provides a superior option to Cit-ORS for the preservation of intestinal blood flow and barrier function and the attenuation of histopathological alterations in enteral resuscitation of rats with burn injury. Its underlying mechanism may be closely related to the pyruvate in activation of intestinal HIF-1-EPO signaling cascades.

Caffeic Acid Phenethyl Ester Alleviates Mesenteric Ischemia/Reperfusion Injury

ABSTRACTPurpose: We aimed to investigate the effects of caffeic acid phenethyl ester (CAPE) on intestinal mucosal injury induced by superior mesenteric occlusion. Methods: This experimental study was conducted on 48 male Wistar-albino rats. The animals were randomly allocated into four groups: (i) Sham-operated group, laparotomy without intestinal ischemia/reperfusion (IR) injury (n = 12); (ii) Sham + CAPE group, identical to group 1 except for CAPE treatment (10 μmol/kg, intravenously) (n = 12); (iii) Intestinal IR group, 60 min of superior mesenteric ischemia followed by 3 hr of reperfusion (n = 12); and (iv) (IR + CAPE)-treated group, 10 μmol/kg injection of CAPE intravenously 30 min before the reperfusion period (n = 12). We evaluated the degree of intestinal mucosal injury on a grading scale, histopathologically, and by measuring oxidative stress markers and antioxidant parameters, biochemically. Intestinal edema was estimated by using wet/dry weight ratios. The plasma proinflammatory cytokine levels were measured. Animal survival was observed up to one week. Results: Intestinal mucosal injury scores were significantly decreased with CAPE administration (p < .05). CAPE treatment significantly reduced oxidative stress markers in the intestinal tissues (p < .05) and the plasma proinflammatory cytokine levels (p < .05), and significantly increased antioxidant parameters in the intestinal tissues (p < .05). Intestinal edema was significantly alleviated by CAPE treatment (p < .05). The survival rates of CAPE-treated IR animals were significantly higher than IR-subjected rats (p < .05). Conclusion: This study clearly showed that CAPE treatment significantly alleviated the intestinal mucosal injury caused by superior mesenteric ischemia/reperfusion. Further clinical studies are required to clarify whether CAPE has a useful role in reperfusion injury during particular surgeries in which IR-induced organ injury occurs.

Antioxidant Treatment Attenuates Intestinal Mucosal Damage and Gut Barrier Dysfunction After Major Hepatectomy. Study in a Porcine Model

BackgroundThis study aims to evaluate whether injury of gut mucosa in a porcine model of post-hepatectomy liver dysfunction can be prevented using antioxidant treatment with desferrioxamine. MethodsPost-hepatectomy liver failure was induced in pigs combining major (70%) liver resection and ischemia/reperfusion injury. An ischemic period of 150 minutes, was followed by reperfusion for 24 h. Animals were randomly divided into a control group (n = 6) and a desferrioxamine group (DFX, n = 6). DFX animals were treated with continuous IV infusion of desferrioxamine 100 mg/kg. Intestinal mucosal injury (IMI), bacterial and endotoxin translocation (BT) were evaluated in all animals. Intestinal mucosa was also evaluated for oxidative markers. ResultsDFX animals had significantly lower IMI score (3.3±1.2 vs. 1.8 ± 0.9, p < 0.05), decreased BT in the portal circulation at 0 and 12 h of reperfusion (p = 0.007 and p = 0.008, respectively), decreased portal endotoxin levels at 6 (p = 0.006) and 24 h (p = 0.004), decreased systemic endotoxin levels (p = 0.01) at 24 h compared to controls. Also, 24 h post-reperfusion mucosal malondialdehyde and protein carbonyls were decreased in DFX animals compared to controls (4.1±1.2 vs. 2.5 ± 1.2, p = 0.05 and 0.5±0.1 vs. 0.4 ± 0.1, p = 0.04 respectively). ConclusionDesferrioxamine seems to attenuate mucosal injury from post-hepatectomy liver dysfunction possibly through blockage of iron-catalyzed oxidative reactions.

EVALUATİON OF EFFECTS OF S-METHYL ISOTHİOUREA AND MELATONİN ON INTESTİNAL ISCHEMİA/REPERFUSİON INJURY IN RATS

The present study was designed to evaluate whether the administration of s-methylisothiourea and melatonin has protective potential in intestinal ischemia/reperfusion injury. Forty male Sprague-Dawley rats were divided into five groups. Ileal specimens were obtained to determine the levels of malondialdehyde, protein carbonyl content, levels of antioxidant enzymes and evaluation of histologic changes. Combination of s-methylisothiourea and melatonin, led to a statistically significant increase in activities of antioxidant enzymes with a decrease in malondialdehyde and protein carbonyl content and intestinal mucosal injury scores. It was shown; combination of SMT and melatonin may exert more promised results.

Effects of aminoguanidine and melatonin on intestinal ischemia/reperfusion injury in rats: An assessor-blinded, controlled experimental study

Background: The reactive oxygen and nitrogen species generated during reperfusion of tissue are characteristic of intestinal ischemia and reperfusion (IIR) injury. Objective: This study was designed to assess whether the administration of aminoguanidine (AG), a selective nitric oxide synthase inhibitor, and/or melatonin has protective potential in IIR injury. Methods: Male Wistar albino rats (age, 3–4 weeks; weight, 100–150 g) were divided in a nonrandom fashion into 5 groups of equal size: group 1, IIR injury + AG 100 mg/kg; group 2, IIR injury + melatonin 10 mg/kg; group 3, IIR injury + AG 100 mg/kg + melatonin 10 mg/kg; group 4, sham operation; and group 5, IIR injury alone. Sixty minutes of intestinal ischemia and 4 hours of reperfusion were carried out in all but the sham-operation group. Ileal specimens were obtained from all rats to determine the extent of histologic changes, measure tissue concentrations of malondialdehyde (MDA) and protein carbonyl (PC), and assess the activity of superoxide dismutase (SOD) and glutathione peroxidase (GPx). Specimens were also assessed and scored by a pathologist blinded to the experiment and the data. Results: Forty rats were divided into 5 groups of 8 each; all 40 survived until study end. In the IIR injury-alone group, mean (SD) MDA concentration and PC content were significantly higher than that of the sham-operation group, and SOD and GPx activity were significantly lower: MDA concentration, 0.86 (0.03) versus 0.54 (0.01) mmol/g protein, respectively; PC content, 0.60 (0.02) versus 0.34 (0.01) mmol/g protein; SOD activity, 104.33 (43.14) versus 2954.72 (109.55) U/g protein; and GPx activity, 10.44 (0.63) versus 24.34 (1.77) U/g protein (all, P < 0.001). Administration of AG, melatonin, and the AG/melatonin combination was associated with significantly higher SOD (1802.31 [102.35], 1776.50 [58.41], and 1924.28 [98.10] U/g protein, respectively) and GPx (17.36 [1.23], 15.96 [1.08], and 18.06 [1.72] U/g protein) activity and significantly lower MDA concentration (0.62 [0.02], 0.64 [0.02], and 0.56 [0.01] mmol/g protein) and PC content (0.53 [0.03], 0.51 [0.01], and 0.49 [0.02] mmol/g protein) compared with the IIR injury-alone group ( P < 0.001). Mean intestinal mucosal injury scores were significantly lower in the 3 treatment groups (2.12 [0.35], 1.75 [0.46], and 1.12 [0.35]) compared with the IIR injury-alone group (3.87 [0.35]; all, P < 0.001). Conclusion: In this study, AG, melatonin, or both administered in combination were associated with improvements in oxidative markers in this rat model of IIR injury.

Curcumin Nutrition for the Prevention of Mesenteric Ischemia–Reperfusion Injury: An Experimental Rodent Model

Background Curcumin is an anti-oxidant molecule known to be a potent inhibitor of nuclear factor-κB (NF-κB). It has been shown to attenuate ischemia/reperfusion (I/R) injury in several organ systems. In this study, we sought to investigate the effects of curcumin on the prevention of superior mesenteric artery I/R injury in rats. Methods Wistar albino rats were randomly allocated to 3 groups: group I, sham operated ( n = 10); group II, I/R injury only ( n = 10); group III, curcumin-treated I/R cohort ( n = 10). Group I animals underwent laparotomy without I/R injury. After group II animals underwent laparotomy, 60 minutes of superior mesenteric artery ligation were followed by 3 hours of reperfusion. In the curcumin group, 15 days before I/R, curcumin (40 mg/kg) was administered by gastric gavage. All animals were sacrificed at the end of reperfusion. Intestinal tissue samples were obtained to investigate intestinal mucosal injury; in addition we estimated levels of myeloperoxidase (MPO) activity, malondialdehyde (MDA), nitric oxide (NO), glutathione (GSH), interleukin (IL)-6, and tumor necrosis factor (TNF)-α. Results There were statistically significant decreases in GSH levels, along with an increase in intestinal mucosal injury scores, MPO activity, MDA levels, NO, IL-6, and TNF-α in group I when compared with groups II and III ( P = .01). Curcumin treatment in group III produced a significant increase in GSH levels, as well as a decrease in intestinal mucosal injury scores, MPO activity, MDA, and NO levels when compared with group II ( P < .05). Conclusion This study showed that curcumin treatment significantly attenuated reperfusion injury in a superior mesenteric artery I/R model in rats.

Tempol reduces bacterial translocation after ischemia/reperfusion injury in a rat model of superior mesenteric artery occlusion

We investigated whether Tempol, a water-soluble antioxidant, prevents the harmful effects of superior mesenteric ischemia/reperfusion on intestinal tissues in rats. The rats were divided into three groups of 10. In group 1, the superior mesenteric artery (SMA) was isolated but not occluded, and in groups 2 and 3 the superior mesenteric artery was occluded for 60 min. After that, the clamp was removed and reperfusion began. In group 3, 5 min before the start of reperfusion, a bolus dose of 30 mg/kg Tempol was administered intravenously and continued at a dose of 30 mg/kg for 60 min. All animals were euthanized after 24 h and tissue samples were collected for analysis. There was a significant increase in myeloperoxidase activity, malondialdehyde levels, and the incidence of bacterial translocation in group 2, with a decrease in glutathione levels. These parameters were found to be normalized in group 3. The intestinal mucosal injury score in group 2 was significantly higher than those in groups 1 and 3. Tempol prevents bacterial translocation while precluding the harmful effects of ischemia/reperfusion injury on intestinal tissues in a rat model of superior mesenteric artery occlusion.

Pyrrolidine dithiocarbamate prevents 60 minutes of warm mesenteric ischemia/reperfusion injury in rats

Background Pyrrolidine dithiocarbamate (PDTC) is a low-molecular-weight thiol antioxidant and potent inhibitor of nuclear factor-κB (NF-κB) activation. It has been shown to attenuate harmful effects of ischemia/reperfusion (I/R) injury in many organs. In recent animal studies, destructive effects of reperfusion injury has been demonstrated. In this study, we aimed to investigate whether PDTC prevents harmful effects of superior mesenteric I/R injury in rats. Methods Wistar-albino rats were randomly allocated into the following 4 groups: (1) sham-operated group—these animals underwent laparotomy without I/R injury (group I, n = 12); (2) sham+PDTC group—identical to sham-operated rats except for the administration of PDTC (100 mg/kg intravenous bolus) 30 minutes prior to the commencement of the experimental period (group II, n = 12); (3) I/R group—these animals underwent laparotomy and 60 minutes of ischemia followed by 120 minutes of reperfusion (group III, n = 12); (4) PDTC-treated group (100 mg/kg, intravenously, before the I/R, group IV, n = 12). All animals were killed, and intestinal tissue samples were obtained for investigation of intestinal mucosal injury, myeloperoxidase (MPO) activity, malondialdehyde (MDA) levels, glutathione (GSH) levels, and intestinal edema. Results There was a statistically significant decrease in GSH levels, along with an increase in intestinal mucosal injury scores, MPO activity, MDA levels, and intestinal tissue wet-to-dry weight ratios in group III when compared to groups I, II, and IV ( P < .05). However, PDTC treatment led to a statistically significant increase in GSH levels, along with a decrease in intestinal mucosal injury scores, MPO activity, MDA levels, and intestinal tissue wet-to-dry weight ratios in group IV ( P < .05). Conclusions This study showed that PDTC treatment significantly prevented the reperfusion injury caused by superior mesenteric I/R. Further clinical studies are needed to clarify whether PDTC may be a useful therapeutic agent to use in particular operations where the reperfusion injury occurs.

Effect of timing of glutamine-enriched enteral nutrition on intestinal damage caused by irradiation

Intestinal mucosal damage and bacterial translocation are clinical problems that may be caused by the use of ionizing radiation. Glutamine (Gln) support reduces the mucosal barrier in several ways. This study was undertaken to investigate the effect of timing of Gln-enriched enteral nutrition (EN) on bacterial translocation and mucosal damage due to radiotherapy (RT). A rat model of whole body irradiation was designed in which a single dose of 485 cGy was given. A total of 50 rats were randomly assigned to the following 5 groups, each of which comprised 10 rats: (1) balanced rat chow given for 8 days without RT (group 1); (2) balanced rat chow given 4 days before and 4 days after RT (group 2); (3) Gln-enriched EN given 4 days before RT (group 3); (4) Gln;enriched EN given 4 days after RT (group 4); and (5) Gln-enriched EN given 4 days before and 4 days after RT (group 5). Mesenteric lymph node and ileum samples were removed for evaluation of bacterial translocation (BT) and histopathologic investigation, respectively. BT and intestinal mucosal injury scores in all rats that received RT were higher than in rats without RT. No difference was seen in parameters between groups 3 and 4 (P>.05, P>.016, respectively); BT and intestinal mucosal injury scores of group 5 were significantly lower than those of groups 3 and 4 (P<.05, P<.016, respectively). Meanwhile, the BT and mesenteric injury scores of group 5 were significantly lower than those of group 2 (P<.05, P<.016, respectively). As a result, intestinal injury due to RT was significantly decreased by Gln-enriched EN support given before and after whole body RT.

Soluble complement receptor type 1 ameliorates the local and remote organ injury after intestinal ischemia-reperfusion in the rat.

We examined the role of C activation in ischemia reperfusion injury by inhibiting C activation in a rat model of mesenteric arterial occlusion. In anesthetized rats, 60 min of mesenteric arterial occlusion was followed by 3 h of reperfusion. PBS alone or containing soluble C receptor 1 (3 or 6 mg) was administered i.v. Controls underwent laparotomy without ischemia. Relative serum C activities were assessed by hemolytic assay, neutrophil (polymorphonuclear leukocyte) sequestration by tissue content of myeloperoxidase (MPO) activity, intestinal mucosal injury by histologic grading, lung vascular permeability by the ratio of bronchoalveolar lavage to blood concentration of radiolabeled BSA, and endothelial cell injury was quantified by measurement of plasma factor VIII-related Ag. After reperfusion, PBS-treated animals had increased intestinal MPO (0.048 +/- 0.007 U/g) compared to sham (0.022 +/- 0.005 U/g (p less than 0.05)) and intestinal mucosal injury score (2.490 +/- 0.221) compared to sham (0.331 +/- 0.045 (p less than 0.05)). Treatment with 6 mg soluble C receptor 1 15 min before reperfusion reduced intestinal MPO (0.017 +/- 0.003 U/g (p less than 0.05)) and mucosal injury (1.733 +/- 0.168 (p less than 0.05)) compared to PBS control. PBS-treated animals also demonstrated increased lung MPO (0.314 +/- 0.025 U/g vs 0.085 +/- 0.018 in sham (p less than 0.05)) and increased lung permeability (bronchoalveolar lavage/blood cpm 11.32 +/- 1.35 x 10(-3) vs sham 2.22 +/- 0.19 x 10(-3) (p less than 0.05)). Treatment with 6 mg soluble C receptor 1 15 min before reperfusion or at reperfusion reduced the lung permeability (bronchoalveolar lavage/blood cpm 3.90 +/- 0.79 x 10(-3) and 5.08 +/- 0.75, respectively (both p less than 0.05)) compared to PBS control, but did not reduce lung MPO (0.342 +/- 0.031 U/g and 0.246 +/- 0.025), respectively. Treatment with sCR1 also reduced the release of factor VIII-related Ag, 5-day mortality, and C hemolytic activity. In this model, C is a major mediator of intestinal injury and extraintestinal injury.