Peripheral leucocyte count variations in rectal cancer treatment.

AIM: Mortality after curative surgery for rectal cancer is increased if surgery is not performed within a week of completed short course radiotherapy. A link to the suppression of leucocytes after neoadjuvant radiotherapy has been suggested. This study investigates the effects of radiotherapy on peripheral leucocyte counts, complications and survival. METHOD: Patient data variables from a retrospective database (Local and National Swedish Registries) of a total of 926 consecutive patients treated for rectal cancer disease at two surgical units (1993-2004) were analysed for leucocyte counts and mortality. In all 310 patients received radiotherapy. Mean follow-up time was 2.8 years. RESULTS: There was a marked suppression of leucocytes in the irradiated groups coupled with a reduction in leucocyte response to surgery (p<0.05) compared to non-irradiated patients. Long course radiotherapy resulted in a better postoperative leucocyte response. Irradiated patients with a low post/preoperative leucocyte ratio had higher complication rates. No association between leucocyte response and survival was seen in the irradiated group. CONCLUSIONS: Postoperative leucocytosis is impaired after neoadjuvant radiotherapy, independent of latency period to surgery. Irradiated patients with a suppression of leucocyte response had significantly higher complication rates. The true extent of survival could not be measured in radiotherapy groups due to the short median follow-up period.

Endotoxin- and D-galactosamine-induced liver injury improved by the administration of Lactobacillus, Bifidobacterium and blueberry.

BACKGROUND: D-galactosamine together with lipopolysaccharide can lead to a pronounced secretion by Kupffer cells of pro-inflammatory mediators, which have been shown to be early and important mediators of liver injury. Probiotics and dietary supplementation with fruit or vegetable extracts with high content of antioxidants, such as blueberry, could be beneficial in protecting against hepatotoxicity. AIMS: To investigate whether blueberry and probiotics could attenuate liver injury induced by D-galactosamine and lipopolysaccharide. SUBJECTS: Sprague-Dawley rats were used. METHODS: Six experimental groups: acute liver injury control and five groups of liver injury treated by blueberry alone or by each of the probiotics strains (Lactobacillus plantarum DSM 15313 and Bifidobacterium infantis DSM 15159) with and without blueberry. Samples were collected 24 h after induction for bacterial test, liver function test, short chain fatty acids, myeloperoxidase, cytokines, malondialdehyde and glutathione. RESULTS: Alanine aminotransferase levels decreased significantly in all groups compared to liver injury control and DSM 15313 groups. Bilirubin, liver TNF-alpha, myeloperoxidase and acetic acid in cecum content decreased significantly in all groups, while liver glutathione values increased significantly in all groups compared to liver injury control. Liver IL-1beta and bacterial translocation to the liver and mesenteric lymph nodes decreased significantly in all groups except B. infantis DSM 15159 group compared to the liver injury control. Enterobacteriaceae count in cecum decreased significantly in the groups with blueberry plus probiotics compared to the other groups. CONCLUSION: Blueberry and probiotics exert protective effects on acute liver injury. They reduce the hepatocytes injury, the inflammation and the pro-inflammatory cytokines, and improve the barrier functions and antioxidant activity.

Manipulation of nitric oxide in an animal model of acute liver injury. The impact on liver and intestinal function

Background: Nitric oxide may have a protective effect on the liver during endotoxemia and chronic inflammation. There is evidence that it maintains liver and intestinal tissue integrity during inflammatory processes. We evaluated the impact of altering nitric oxide release on acute liver injury; the associated gut injury and bacterial translocation; at different time intervals. Methods: An acute rat liver injury model induced by D-galactosamine was used. Sprague Dawley rats were divided into four main groups: normal control; acute liver injury control; acute liver injury + N-nitro-L-arginine methyl ester (L-NAME); acute liver injury + L-NAME + L-arginine. Each group was divided into three subgroups according to the different time intervals (6; 12; 24 hours) after the induction of the liver injury. Liver enzymes and bilirubin were evaluated; as well as bacterial translocation; cecal and colonic microflora; and histological study of liver; ileum and cecum. Results:Liver enzymes increased significantly at all time intervals in acute liver injury + L-NAME compared to liver injury control groups. Bacterial translocation increased significantly in liver injury + L-NAME groups; at 6 hours to the liver; at 12 hours to the liver and mesenteric lymph nodes (MLNs); and at 24 hours to arterial and portal blood; liver and MLNS. Inhibition of nitric oxide increased significantly the Enterobacteriaceae count in cecum compared to normal and liver injury control groups. The G-negative anaerobes increased significantly in the colon compared to the liver injury control group. Conclusion: Inhibition of nitric oxide in an acute liver injury model potentiates the liver injury as evidenced by increased appearance of hepatocellular necrosis and elevated liver enzymes and bilirubin. It increases the Enterobacteriaceae in both cecum and colon and G-negative anaerobes in the colon. It also increases bacterial translocation to extra-intestinal sites. The increased bacterial translocation could be one of the mechanisms potentiating liver injury and nitric oxide may be pathophysiologically involved. Further studies are required to confirm this hypothesis

Identification of the translocating bacteria in rats with acute liver injury and their relation to the bacterial flora of the intestinal mucosa.

The bacterial flora of the intestine and the bacteria found in liver, mesenteric lymph nodes, portal and arterial blood after D-galactosamine-induced liver injury, with and without pretreatment with Lactobacillus plantarum DSM 9843, were studied in the rat. Dominating representatives were identified to species level by 16S rDNA sequencing and typed by randomly amplified polymorphic DNA (RAPD) and by restriction endonuclease analysis (REA) for strain definition. It was proven that bacterial strains from the intestine occur at extraintestinal sites after liver injury. Lactobacillus spp. dominated the intestinal flora and were also the most frequently found genus in the liver and the mesenteric lymph nodes. Some of the blood isolates, identified as Staphylococcus aureus, Proteus vulgaris and Bacteroides merdae, were not found as a dominating part of the mucosal flora. Treatment with L. plantarum before liver injury decreased translocation and made the intestinal flora increasingly dominated by lactobacilli.

Inhibition of matrix metalloproteinases enhances breaking strength of colonic anastomoses in an experimental model.

BACKGROUND: The breaking strength of colonic anastomoses declines after operation to a minimum at days 3-4, with a subsequent risk of anastomotic dehiscence. The mechanism is thought to be collagen degradation by matrix metalloproteinases (MMPs). This study examined the pathogenic role of MMPs on the mechanical strength of colonic anastomoses by giving the synthetic broad-spectrum MMP inhibitor BB-1101 systemically. METHODS: Forty-eight male Sprague-Dawley rats were treated daily for 7 days with BB-1101 30 mg/kg or vehicle alone (control) starting 2 days before operation. The breaking strength of standardized left-sided colonic anastomoses was measured on postoperative days 1, 3 and 7. RESULTS: Serum BB-1101 levels were increased at 100 nmol/l in BB-1101-treated rats. The anastomotic breaking strength was 48 per cent higher (P = 0.02) in BB-1101-treated animals compared with controls on postoperative day 3. Neither collagen accumulation nor infiltration of neutrophils in the anastomotic area was influenced by BB-1101 treatment. Net deposition of new collagen in subcutaneous sponges was unaffected by the BB-1101. CONCLUSION: The enhanced breaking strength of colonic anastomoses during the critical early postoperative phase found after administration of a broad-spectrum MMP inhibitor implies that MMPs might increase the risk of anastomotic dehiscence. Presented in part to the third joint meeting of the European Tissue Repair Society and the Wound Healing Society in Bordeaux, France, 24-28 August 1999, and published in abstract form in Wound Repair Regen 1999; 7: A321

Administration of Lactobacillus plantarum 299v reduces side-effects of external radiation on colon anastomotic healing in an experimental model.

OBJECTIVE: Preoperative radiotherapy of patients with rectal carcinoma is frequently used to reduce the incidence of local recurrence. However, the radiation therapy is associated with several complications, including diarrhea, retarded anastomotic healing and mucosal atrophy. Exogenous administration of lactobacilli has been demonstrated to be effective in stimulating intestinal mucosal growth and reduce mucosal inflammation. The objective of this study was to examine the effects of Lactobacillus plantarum 299v administration on external radiation injury in colon anastomotic healing at different time points. MATERIAL AND METHODS: Sprague-Dawley rats were treated with Lb. plantarum 299v or saline as control and received external radiation of the lower abdomen (10 Gy/day) on day 3 and 7 of the experiment. After 4 days, a colonic resection with anastomosis was performed. Animals were sacrificed on 4th, 7th and 11th day postoperatively. Body weight, white blood cell (WBC) count, mucosal myeloperoxidase (MPO) activity, hydroxyproline, nucleotide, DNA and RNA content, colonic bacterial microflora, bacterial translocation and histology were evaluated. RESULTS: On the 4th postoperative day body weight, WBC and MPO decreased significantly after radiation. On the 7th postoperative day MPO decreased after radiation. In the two irradiated groups it decreased significantly in the Lb. plantarum group compared to the radiated group without treatment. Collagen concentration on the 7th postoperative day was significantly higher in Lb. plantarum group without radiation compared to the group with radiation without Lb. plantarum. On the 11th postoperative day MPO was significantly higher in irradiated rats without treatment compared to Lb. plantarum treatment. The collagen concentration increased significantly in the irradiated Lb. plantarum group compared to the other two groups. CONCLUSION: The collagen content decreased and MPO activity increased significantly of the colonic anastomosis in irradiated rats without treatment compared to those treated with Lb. plantarum. It therefore seems that administration of Lactobacillus plantarum 299v reduces the intestinal injury and inflammation following external radiation and improves the colonic anastomotic healing.

Effects of different probiotic strains of Lactobacillus and Bifidobacterium on bacterial translocation and liver injury in an acute liver injury model.

Septic complications represent frequent causes of morbidity in liver diseases and following hepatic operations. Most infections are caused by the individual own intestinal microflora. The intestinal microflora composition is important in physiological and pathophysiological processes in the human gastrointestinal tract, but their influence on liver in different situations is unclear. We therefore studied the effect of different Lactobacillus strains and a Bifidobacterium strain on the extent of liver injury, bacterial translocation and intestinal microflora in an acute liver injury model. Sprague-Dawley rats were divided into five groups: acute liver injury control, acute liver injury + B. animalis NM2, acute liver injury + L. acidophilus NMI, acute liver injury + L. rhamnosus ATCC 53103, and acute liver injury + L. rhamnosus DSM 6594 and L. plantarum DSM 9843. The bacteria were administered rectally daily for 8 days. Liver injury was induced on the 8th day by intraperitoneal injection of D-galactosamine (1.1 g/kg BW). Samples were collected 24 h after the liver injury. Liver enzymes and bilirubin serum levels, bacterial translocation (to arterial and portal blood, liver and mesenteric lymph nodes (MLNs)), and intestinal microflora were evaluated. L. acidophilus NM1; L. rhamnosus ATCC 53103, and L. rhamnosus DSM 6594 + L. plantarum DSM 9843 decreased bacterial translocation compared to the liver injury control group. B. animalis NM2 increased bacterial translocation to the mesenteric lymph nodes. The levels of alanine aminotransferase (ALAT) were significantly lower in the L. acidophilus, L. rhamnosus ATCC 53103, L. rhamnosus DSM 6594 + L. plantarum DSM 9843 groups compared to the liver injury group. The L. rhamnosus and L. rhamnosus + L. plantarum groups significantly reduced ALAT levels compared to the B. animalis group. All administered bacteria decreased the Enterobacteriaceae count in the cecum and colon. Administration of different lactobacilli and a Bifidobacterium strain in an acute liver injury rat model, has shown different effects on bacterial translocation and hepatocellular damage. L. acidophilus, L. rhamnosus, and L. rhamnosus + L. plantarum reduced bacterial translocation and hepatocellular damage. B. animalis NM2 increased bacterial translocation to the mesenteric lymph nodes and did not affect hepatocellular damage.

Inhibition of nitric oxide production and the effects of arginine and Lactobacillus administration in an acute liver injury model.

OBJECTIVE: To study the effect of inhibiting nitric oxide production and the effects of arginine and lactobacilli administration in an acute liver injury (LI) model. SUMMARY BACKGROUND DATA: Infectious complications caused by enteric bacteria are common in patients with liver diseases and those who have undergone liver surgery. Increased bacterial translocation has been proposed as one underlying mechanism. Lactobacilli constitute an integral part of the normal gastrointestinal microecology; they are involved in host metabolism and have many beneficial properties. Arginine has numerous roles in cellular metabolism and may be metabolized by lactobacilli in some cases. We have previously shown that rectal administration of Lactobacillus plantarum DSM 9843 (strain 299v), with and without arginine, in an acute LI model significantly reduces the extent of the LI and reduces bacterial translocation. To clarify the pathogenetic mechanisms, we studied the role of nitric oxide in the effects of L. plantarum and arginine in acute LI, as determined by bacterial translocation, ileal, cecal, and colonic nucleotides, RNA, and DNA. METHODS: Male Sprague-Dawley rats were used. L. plantarum, 2% arginine, and/or N-nitro-L-arginine methyl ester (L-NAME), as appropriate, were administered rectally once daily for 8 days. Acute LI was induced on the eighth day by intraperitoneal injection of D-galactosamine (1.1 g/kg body weight), and samples were collected after 24 hours. Bacterial translocation was evaluated by culture of portal and arterial blood, mesenteric lymph nodes, and liver tissue. Liver enzymes and bilirubin were assayed in the serum. The bacterial load in the cecum and colon was determined. Ileal, cecal, and colonic mucosal nucleotides, RNA, and DNA were evaluated. RESULTS: The levels of liver enzymes and bilirubin were lower in liver-injured rats supplemented with arginine and Lactobacillus, and this effect was abolished by the addition of L-NAME. Inhibition of nitric oxide production (by L-NAME) increased bacterial translocation in many groups. L-NAME administration increased the cecal and colonic bacterial count and decreased the levels of mucosal nucleotides, RNA, and DNA. CONCLUSIONS: Inhibition of nitric oxide production modulated the effects of arginine and L. plantarum in this acute LI model. L-NAME potentiated the LI, as indicated by elevation of liver enzymes and bilirubin, and it also increased bacterial translocation and the cecal and colonic bacterial count. Increased bacterial translocation could be one of the mechanisms by which LI is potentiated.

Inhibition of nitric oxide modulates the effect of oral arginine supplementation in acute liver injury.

BACKGROUND: Arginine possesses numerous unique and advantageous biochemical and pharmacologic properties. We have previously shown that arginine supplementation in an acute liver injury model reduces both the extent of the liver injury and bacterial translocation. We therefore studied the role of nitric oxide on the effects of oral arginine supplementation in acute liver injury, bacterial translocation, ileal and cecal mucosal nucleotides, and RNA and DNA, to investigate pathogenetic mechanisms. METHODS: Sprague-Dawley rats were divided into normal, liver injury control, N-nitro-L-arginine methyl ester (L-NAME), arginine, and L-NAME + arginine supplementation groups. Oral supplementation was performed daily through a nasogastric tube for 8 days. Acute liver injury was induced on the 8th day by intraperitoneal injection of D-galactosamine (1.1 g/kg body weight). Twenty-four hours after the liver injury, liver function tests, bacterial translocation, and ileal and cecal mucosal nucleotides, RNA, and DNA were evaluated. RESULTS: Bilirubin and liver enzymes increased significantly in the L-NAME group compared with the arginine group, whereas the liver enzymes increased significantly compared with the liver injury control group. In the L-NAME group the number of bacteria translocated to the portal and arterial blood increased significantly compared with all groups. In the arginine group the bacteria translocated to the liver and mesenteric lymph nodes decreased significantly compared with the liver injury control and L-NAME groups. The ileal and cecal mucosal nucleotides, RNA, and DNA in the arginine group increased significantly compared with the normal, liver injury, and L-NAME groups. CONCLUSIONS: Nitric oxide plays a role in the beneficial effect of the arginine supplementation in acute liver injury. It significantly improves the liver damage indicated by the increase of liver enzymes when its production was inhibited by L-NAME. Nitric oxide has a role in bacterial translocation since the number of bacteria significantly increased in arterial and portal blood when L-NAME was used to inhibit its production. Furthermore, arginine supplementation improved mucosal nucleotides, RNA, and DNA in ileum and colon.

Effect of Lactobacillus supplementation with and without arginine on liver damage and bacterial translocation in an acute liver injury model in the rat.

In acute liver failure following hepatitis, toxic insults, or after major liver surgery, there is an increased bacterial translocation from the gut. This may explain some of the infectious complications seen in these conditions. To elucidate mechanisms and find possible preventive measures, we investigated the effect of rectal administration of arginine and probiotic bacteria (Lactobacillus spp.) on bacterial translocation and the extent of liver failure. Sprague-Dawley rats were used and five different Lactobacillus strains (Lb. reuteri R2LC, Lb. rhamnosus DSM 6594 (= strain 271), Lb. plantarum DSM 9843 (= strain 299v), Lb. fermentum 8704:3 (= strain 245), and Lb. reuteri (= strain 108) were administered rectally once daily for 8 days with and without 2% arginine. Acute liver injury (ALI) was induced on the eighth day by intraperitoneal injection of D-galactosamine (1.1 g/kg body weight), and samples were collected after 24 and 48 hours. Bacterial translocation was evaluated by bacterial culture from portal and arterial blood, mesenteric lymph nodes, and liver tissue. Liver enzymes and bilirubin were evaluated in the serum. The bacterial load in the cecum and colon was determined and the liver histopathological changes were studied. There was no mortality at any time. The liver enzymes and bilirubin decreased in some of the groups supplemented with lactobacilli with and without arginine compared with the ALI control group. The incidence of bacterial translocation and the number of the translocated bacteria decreased significantly in some of the supplemented groups. Lb. plantarum + arginine administration significantly reduced the level of the released liver enzymes, hepatocellular necrosis and inflammatory cell infiltration, bacterial translocation, and the number of Enterobacteriaceae in the cecum and colon. Rectal administration of different Lactobacillus strains with and without arginine in an ALI model significantly modulates the extent of the liver failure and reduces bacterial translocation. Lb. plantarum DSM 9843 (= strain 299v) with or without arginine seemed superior to the other Lactobacillus strains. The beneficial effect of arginine administration alone indicates a possible role of nitric oxide and polyamines in this process, and the lactobacilli may execute their action via the same mechanisms or via bacterial antagonism and/or enhancement of systemic and intestinal mucosal immunity.

Effect of oral supplementation of lactobacilli on bacterial translocation in acute liver injury induced by D-galactosamine.

BACKGROUND/AIM: Bacterial infections and sepsis are frequent complications of acute liver injury, with a high share in the mortality and morbidity of this condition. Bacterial translocation from the gut may play an important role in the high rate of infections observed. In this experiment the effect of different oral supplementation on bacterial translocation was evaluated in acute liver injury induced by D-galactosamine in the rat. METHODS: Rats were given oral supplements of lactulose, neomycin, Lactobacillus reuteri R2LC, and Lactobacillus plantarum DSM 9843 for 1 week. Liver injury was induced by intraperitoneal administration of 1.1 g/kg D-galactosamine. Twenty-four hours later, rats were sacrificed and liver enzymes and histology, intestinal bacterial count and microflora, intestinal mucosal histology, DNA and RNA content, bacterial translocation to blood, mesenteric lymph nodes, and liver, and serum endotoxin were studied or measured. RESULTS: Lactulose was highly effective in prevention of liver injury and bacterial translocation. Neomycin and Lactobacillus plantarum DSM 9843 showed a moderate effect in prevention of liver injury and bacterial translocation. Intestinal bacterial count and microflora were affected by different treatment modalities. No endotoxin concentration was found in any of the experimental groups. Both lactobacilli could significantly improve the mucosal proliferative state. CONCLUSIONS: Oral supplementation of lactulose with anti-endotoxin effect could successfully prevent the liver injury and the subsequent bacterial translocation in acute liver injury induced by administration of D-galactosamine in the rat. This effect was irrespective of the intestinal bacterial alteration or mucosal proliferative state.

The effects of Lactobacillus strains and oat fiber on methotrexate-induced enterocolitis in rats.

BACKGROUND & AIMS: Administration of methotrexate to rats on an elemental diet results in severe enterocolitis and death. Lactobacilli, an integral part of the healthy gastrointestinal microecology, may provide therapeutic benefits to help the recovery from enterocolitis. The purpose of this study was to evaluate the effects of lactobacilli and oatbase on methotrexate-induced enterocolitis in rats. METHODS: Rats received continuous intragastric infusion of elemental diet or with supplementation of oatbase, Lactobacillus reuteri R2LC, and Lactobacillus plantarum DSM 9843, with and without fermentation, from the beginning of the study. Methotrexate (20 mg/kg) was injected intraperitoneally on day 3, and the sampling was performed on day 6. RESULTS: Lactobacilli and oatbase decreased body weight loss and intestinal permeability and increased bowel mucosal mass in enterocolitic rats. Administration of lactobacilli, but not oatbase, decreased the intestinal myeloperoxidase level, reestablished intestinal microecology, and reduced bacterial translocation to extraintestinal sites. Both lactobacilli and oatbase reduced plasma endotoxin levels. The effects of lactobacilli were greater with fermentation than without fermentation or oatbase alone, and L. plantarum was more effective in reducing intestinal pathogens than L. reuteri. CONCLUSIONS: Exogenous administration of lactobacilli, especially L. plantarum with fermentation, is helpful in reducing the severity of enterocolitis in rats.

The effect of pretreatment with endotoxin and lactobacillus on bacterial translocation in acute liver injury.

OBJECTIVE: To evaluate the effect of pretreatment with endotoxin or Lactobacillus reuteri pretreatment on bacterial translocation after acute liver injury. DESIGN: Experimental study. SETTING: University department, Sweden. SUBJECTS: 96 Sprague-Dawley rats were divided into four groups of 24 each. Three of them received intraperitoneal D-galactosamine, the fourth received pyrogen free water and was used as the normal control. Twenty-four hours later the study was terminated and samples collected. INTERVENTIONS: Endotoxin and L reuteri R2LC were injected intraperitoneally three days, one week, and two weeks before induction of liver injury. MAIN OUTCOME MEASURES: Extent of liver injury and bacterial translocation to mesenteric lymph nodes, liver, and systemic blood. RESULTS: The extent of liver injury and rate of bacterial translocation were lower three days after pretreatment with endotoxin, than after pretreatment with L reuteri. There was no other difference among the other groups. High concentrations of serum endotoxin were detected three days after pretreatment with endotoxin. There were no significant changes in small intestinal and caecal bacterial counts. CONCLUSION: Pretreatment with endotoxin effectively prevented liver injury by D-galactosamine and subsequent bacterial translocation. Pretreatment with L reuteri had no beneficial effect.

Oral arginine supplementation in acute liver injury.

Acute liver failure is accompanied by a high rate of bacterial and septic complications. Arginine has a potent effect on the immune system and modulates bacterial clearance in septic models. We studied the effect of oral arginine supplementation on the extent of liver injury and the associated bacterial translocation in an acute liver injury model in rats. Sprague-Dawley rats were divided into normal, liver injury, and arginine supplemented groups. In the arginine group, 2% arginine was supplemented daily through a nasogastric tube for 8 d. Acute liver injury was induced on the eighth day by intraperitoneal injection of D-galactosamine (1.1 g/kg body wt). Samples were collected 24 h after the liver injury. In the arginine-supplemented group, alkaline phosphatase, bilirubin, and aspartate aminotransferase were reduced significantly compared with the acute liver injury control group. The results of bacterial translocation in the arginine-supplemented group showed a significantly reduced number of translocated bacteria to the liver and mesenteric lymph nodes than occurred in the acute liver injury group. The histological study of the liver in arginine-supplemented group showed scattered areas of hepatocellular necrosis and inflammatory cell infiltration, and in the acute liver injury group there were more and widespread hepatocellular necrosis and inflammatory cell infiltration. Oral supplementation of arginine in an acute liver injury model improves significantly the state of the liver injury and reduces bacterial translocation to the liver and mesenteric lymph nodes.

Pectin-supplemented enteral diet reduces the severity of methotrexate induced enterocolitis in rats.

BACKGROUND: Administration of methotrexate (MTX) to rats fed an elemental diet results in a high mortality from severe enterocolitis. Previous studies have shown that pectin is an important precursor of substrates for intestinal structure and function and may facilitate intestinal recovery after enterocolitis. The aim of this study is to evaluate the effect of pectin on MTX-induced enterocolitis in rats. METHODS: Rats received intragastric infusion of either 1% pectin-supplemented or pectin-free elemental diet from the beginning of the study via a gastrostomy. On the 4th day animals received either MTX, 20 mg/kg intraperitoneally, or saline injection and were killed on the 7th day for sampling. RESULTS: Pectin supplementation significantly decreased body weight loss, organ water content, and intestinal myeloperoxidase levels and increased mucosal protein, DNA, and RNA content in enterocolitis rats. The intestinal permeability was increased by administration of MTX, and pectin supplementation significantly reversed the increased permeability in the distal small bowel and colon. Pectin supplementation also lowered the magnitude of bacterial translocation, decreased plasma endotoxin levels, and restored bowel microecology. CONCLUSIONS: Pectin significantly decreased MTX-induced intestinal injury and improved bowel integrity.

The effect of endotoxin and Lactobacillus pretreatment on peritoneal macrophage behavior in acute liver injury in rat.

The effect of endotoxin and Lactobacillus R2LC pretreatment in acute liver injury, induced by D-galactosamine was studied. Administration of D-galactosamine resulted in much higher luminescent activity than the control (49.24 mV vs 19.75 mV), while there was no change detected on the metabolic response to phorbol-12-myristate-13-acetate (PMA) stimulation in the calorimeter. Pretreatment of animals with intraperitoneal administration of heat-killed Lactobacillus resulted in higher oxygen free radical production (105.46 mV) and a much higher metabolic response to PMA in microcalorimeter (24.63 pW per cell vs 13.03 in the control). On the other hand pretreatment with endotoxin resulted in higher luminometric response to PMA compared to liver injury group (65.87 mV), and no response in the microcalorimeter at all. Phagocytic activity was decreased from 86 to 59% after administration of D-galactosamine, and was not significantly influenced by any of the pretreatment modalities. This experiment showed that pretreatment with Lactobacillus resulted in increased macrophage metabolic activity, while endotoxin pretreatment rendered the macrophages unresponsive to subsequent stimulation. These findings may explain why pretreatment with endotoxin is beneficial in acute liver injury induced by D-galactosamine, but not with gram-positive bacteria including Lactobacillus.

Dynamics of bacterial translocation in acute liver injury induced by D-galactosamine in rat.

Bacterial translocation may play a role in acute liver injuries as high rates of infectious and septic complications are observed in these clinical conditions. Increased passage of endotoxin and translocating bacteria not only potentiates the extent of liver injury, but may also play a determining role in its final outcome. In this paper the incidence of bacteria] translocation in acute liver injury in rats is evaluated with other important pathological changes observed at different time points after liver injury induced by intraperitoneal administration of D-galactosamine. The bacterial translocation to the blood and other extraintestinal sites starts 3 h after induction of liver injury and is not found to be related to light microscopic changes in the liver or ileal or cecal mucosa, detectable levels of endotoxin in the portal blood, or DNA changes in the small and large intestinal mucosa, but corresponds to the release of liver enzymes in the serum.