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Objectives We investigated the positive effect of silibinin after IV administration as silibininhydroxypropyl-ß-cyclodextrin lyophilized product, by measuring gene expression and liver tissue protein levels of tumor necrosis factor-a, interleukin-6, monocyte chemoattractant protein-1, matrix metalloproteinases matrix metalloproteinases and tissue inhibitor of matrix metalloproteinases-2. Methods 63 Wistar rats of age 13.24±4.40 weeks underwent ischemia/reperfusion (I/R) injury of the liver. The animals were randomized into three groups: Sham (S; n = 7); Control (C; n-28); silibinin (Si; n-28). The C and Si groups underwent 45 min ischemia. Si received silibinin-hydroxypropyl-ß-cyclodextrin intravenously immediately before reperfusion at a dose of 5 mg/kg. Both groups were further divided into 4 subgroups, based on euthanasia time (i.e., 60, 120, 180 and 240 min). Key findings qRT-PCR results confirmed the statistically significant reduction of the expression of the pro-inflammatory factors at 240 min after I/R injury (tumor necrosis factor-a: P < 0.05; MCR1: P < 0.05) and matrix metalloproteinases (matrix metalloproteinases 2: P < 0.05; matrix metalloproteinases 3: P < 0.05) and the increase of tissue inhibitor of matrix metalloproteinases-2 in liver tissue in the Si group. Moreover, results of immunohistochemistry levels confirmed that at 240 min pro-inflammatory factors (tumor necrosis factor-a: P < 0.05; MCR1: P < 0.05) and matrix metalloproteinases (matrix metalloproteinases 2: P < 0.05; matrix metalloproteinases 3: P < 0.05) had a statistically significantly lower expression in the Si group while tissue inhibitor of matrix metalloproteinases-2 had a higher expression. Conclusions Silibinin may have a beneficial effect on the protection of the liver. [ABSTRACT FROM AUTHOR]

Introduction: we present a rat experimental model used to evaluate the possible reduction in the extent of pancreatic tissue injury in acute pancreatitis cases, after administration of eugenol. Methods: one hundred and twenty Wistar rats were used, which were randomly assigned in 3 groups: sham (n=20), control (n=50) and eugenol (n=50). Acute pancreatitis was induced by biliopancreatic ligation in the control and eugenol groups, but not in the Sham group. In the eugenol group, eugenol was administered per-os. Five histopathological parameters, such as edema, inflammatory infiltration, duct dilatation, hemorrhage and acinar necrosis were evaluated. Results: at 72 h from acute pancreatitis induction, the total histological score was diminished in the eugenol group (p<0.0005) and duct dilatation and inflammatory infiltration were reduced compared to the control group (p<0.05). In addition, at 72 h, eugenol reduced pancreatic myeloperoxidase activity (p<0.0005). Conclusion: eugenol, a highly free radical scavenger agent, may have a preventive role in acute pancreatic injury, as it was evident in our rat experimental model. [ABSTRACT FROM AUTHOR]

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Background: Remote kidney damage is a sequel of hepatic ischemia-reperfusion (I/R) injury. Silibinin is the main ingredient of the milk thistle plant seed extract with known antioxidant and hepatoprotective activity. Our study investigates the nephroprotective potential of intravenously administered silibinin, as a lyophilized SLB-hydoxypropyl-beta-cyclodextrin product, in hepatic I/R injury. Material and methods: 63 Wistar rats were divided into three groups: Sham (virtual intervention); Control (45 min ischemia and reperfusion); and Silibinin (200 μL intravenous silibinin administration after 45 min of ischemia). Kidney tissues were collected to determine TNF-α, M30 and histopathological changes at predetermined time intervals. Results: Comparing Sham vs. Control groups, proved that hepatic I/R injury increased renal TNF-α and M30 expression. Deterioration was observed in hyperemia/filtration of renal parenchyma and tubules, cortical filtration, tubular necrosis and edema (tissue swelling index). Intravenous silibinin administration and comparison of the Control vs. Silibinin groups showed a statistically significant decrease in TNF-α levels at 240 min following I/R (p < 0.0001), and in M30 at 180 min (p = 0.03) and 240 min (p < 0.0001). Renal parameters have significantly decreased in: hyperemia/filtration of renal parenchyma at 120 min (p = 0.003), 180 min (p = 0.0001) and 240 min (p = 0.0002); hyperemia/filtration of renal tubules at 120 min (p = 0.02), 180 min (p = 0.0001) and 240 min (p = 0.0005); cortical filtration (240 min - p = 0.005); tubular necrosis (240 min - p = 0.021); and edema (240 min - p = 0.001). Conclusion: Our study confirms that hepatic I/R injury causes remote renal damage while the intravenous administration of silibinin leads to statistically significant nephroprotective action. [ABSTRACT FROM AUTHOR]

Introduction: Acinar cell death is a crucial event in acute pancreatitis (AP) and may occur either by apoptosis or necrosis. The aim of this study was to investigate the expression of the apoptosis associated proteins Fas and FasL in experimentally induced severe AP. Methods: AP was induced in 30 rats by injecting 0.2 ml of 4.5% sodium taurocholate solution into the biliopancreatic duct. Sham operated animals ( n = 30) and 10 normal controls were used for comparisons. Animals were killed at 6, 12, 24, 48, 72 hr and 1 week after operation (five animals at each time point) and both serum and pancreatic tissue were obtained. The severity of AP was graded by morphological evaluation and by measuring serum amylase levels. Acinar cell apoptosis was detected by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay. Tissue expressions of Fas and FasL were evaluated by immunohistochemistry. Results: Sodium taurocholate injection resulted in severe acute necrotizing pancreatitis as early as six hr after taurocholate infusion with gradually increasing severity and a peak at 72 hr, and a significant increase of serum amylase at 6 and 12 hr. Apoptotic acinar cells were observed between 48 and 72 hr. The expression of both Fas and FasL in pancreatic tissue was induced in comparison with normal controls. Fas expression in AP was higher and statistically significant at 24 hr whereas FasL expression was consistently lower with a statistical significance observed at 12 hr when compared to sham-operated animals suggesting Fas upregulation and FasL downregulation in this model of AP. Conclusions: Induction and sequential changes in the expressions of Fas and FasL occur during taurocholate induced severe AP in rats and their temporal modulation might associate with acinar cell death by apoptosis. [ABSTRACT FROM AUTHOR]

Introduction: Smoking is associated with loss of body weight (BW) and reduced appetite, while smoking abstinence with the opposite effect. The role of peripheral signaling by appetite-controlling hormones leptin and ghrelin is not clear. In the present study, the relationship of circulating leptin and ghrelin with BW and food intake rate (FIR) changes was studied during cigarette smoke exposure (CSE) and after its cessation in the rat. Methods: Male Wistar rats were subjected to CSE for 8 weeks by confinement to plexiglass chambers (Group S). Control animals were confined to identical chambers without smoke (Group C). During CSE and an equivalent follow-up period, BW and FIR was recorded and serum leptin and ghrelin levels were measured. Results: A sharp decrease in BW was noted during the first 4 weeks of CSE, while FIR, after a substantial decrease noted at Week 1, returned to control levels. Thereafter, rats started to regain their BW until they reached control levels by the 1st week postCSE. BW regain was accompanied by a rebound increase of FIR, which plateaued during the first 4 weeks postCSE and then normalized. Serum leptin was decreased in Group S during both periods, normalizing at the 7th week postCSE. Ghrelin levels did not differ between groups. Conclusions: Circulating leptin could not explain by its own BW and FIR changes during the first few week of CSE in rats, in contrast to the rest of the CSE period as well as after its cessation. Serum ghrelin levels did not justify BW and FIR changes. [ABSTRACT FROM AUTHOR]

The aim of the present study was to assess the survival of free and immobilized Lactobacillus casei ATCC 393 on apple pieces, contained in probiotic-fermented milk, after gastrointestinal (GI) transit and to investigate the potential regulation of intestinal microbial flora in a rat model. In in vitro GI stress tolerance tests, immobilized L. casei ATCC 393 exhibited significantly higher survival rates compared to free cells. At a second stage, probiotic-fermented milk produced by either free or immobilized cells was administered orally at a single dose or daily for 9 days in Wistar rats. By 12 h after single-dose administration, both free and immobilized cells were detected by microbiological and molecular analysis at levels ≥6 logCFU/g of feces. Moreover, daily administration led to significant reduction of staphylococci, enterobacteria, coliforms and streptococci counts. In conclusion, L. casei ATCC 393 contained in fermented milk survived GI transit and modulated intestinal microbiota. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Aim: The aim of the present study is to evaluate pathologic changes in the pancreatic parenchyma in an experimental model of acute pancreatitis (AP) following bilio-pancreatic duct ligation. An effort was made to clarify the role of apigenin, a substance that is well-known for its antioxidant and anti-inflammatory role and its likely beneficial activity to the pancreatic parenchyma following AP in rats. Material and method: One hundred twenty-six male Wistar rats 3–4 mo old and weighing 220–350 g were used. At time 0, the following groups were randomly assigned: group sham: rats were subjected to virtual surgery; group control: rats were subjected to surgery for induction of AP, by ligation of the bilio-pancreatic duct; group apigenin: rats were subjected to surgery for induction of AP and enteral feeding with apigenin. Pathologic changes of the pancreatic parenchymal and myeloperoxidase activity were measured at predetermined time intervals 6, 12, 24, 48, and 72 h. Result: From the pathologic reports, by comparing the control group with the apigenin group, an improvement of pancreatic tissue architecture following apigenin administration was observed. Inflammatory infiltration, edema, ductal dilation, and necrosis were reduced following apigenin administration over time (P = 0.049, P = 0.228, P = 0.387, P = 0.046). Treatment with apigenin significantly reduced the bilio-pancreatic duct ligation and evoked an increase in pancreatic myeloperoxidase activity (P = 0.030). Conclusion: Oral apigenin administration in rats, following experimentally induced pancreatitis, seems to protect the pancreatic tissue. Thus, apigenin administration to humans could potentially ameliorate the damages to the pancreas. [Copyright &y& Elsevier]

Abstract: Adhesion to the intestine represents a critical parameter for probiotic action. In this study, the adhesion ability of Lactobacillus casei ATCC 393 to the gastrointestinal tract of Wistar rats was examined after single and daily administration of fermented milk containing either free or immobilized cells on apple pieces. The adhesion of the probiotic cells at the large intestine (cecum and colon) was recorded at levels ≥6 logCFU/g (suggested minimum levels for conferring a probiotic effect) following daily administration for 7 days by combining microbiological and strain-specific multiplex PCR analysis. Single dose administration resulted in slightly reduced counts (5 logCFU/g), while they were lower at the small intestine (duodenum, jejunum, ileum) (≤3 logCFU/g), indicating that adhesion was a targeted process. Of note, the levels of L. casei ATCC 393 were enhanced in the cecal and colon fluids both at single and daily administration of immobilized cells (6 and 7 logCFU/g, respectively). The adhesion of the GI tract was transient and thus daily consumption of probiotic products containing the specific strain is suggested as an important prerequisite for retaining its levels at an effective concentration. [Copyright &y& Elsevier]

Background: The objectives of the present study were to test the hypothesis that hepatocyte regenerating activity induced by radiofrequency ablation (RFA) of the liver is attenuated when performed under Pringle maneuver, and to investigate the potentially protective effect of mesna prophylactic administration. Materials and Methods: Wistar rats were subjected to liver RFA (group RFA), RFA plus Pringle maneuver for 30min (group RFA+P), RFA plus Pringle plus mesna (400mg/kg, per os, 3h prior to operation) (group RFA+P+M), Pringle only (group P), or sham operation (group S) after midline laparotomy. At 1h, liver oxidative state (glutathione to glutathione disulfide ratio–GSH/GSSG) and nuclear factor κB (NF-κB) activity were assessed in liver specimens. At 1, 3, and 6h, the levels of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) were measured in blood serum. At 24h, 48h, 1wk, and 3 wk, the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured in blood serum and the histopathologic profile and hepatocyte mitotic activity were assessed in liver specimens. Results: Mitotic activity was low but sustained in groups RFA and RFA+P+M, more intense in group P, while suppressed in group RFA+P. Histopathologic profile was deteriorated with lesions being more intense in group RFA+P but significantly less severe in group RFA+P+M. Oxidative stress was equally induced in all experimental groups. NF-κB was activated in groups RFA, RFA+P, and P, but not in group RFA+P+M. IL-6 and TNF-α serum levels were increased; the levels were significantly higher in group RFA+P, while lower in group RFA+P+M. Serum transaminases levels were increased during the first 48h. Conclusions: Hepatocyte regenerating activity is suppressed following liver RFA under Pringle maneuver. Prophylactic administration of mesna preserves hepatocyte regenerating capacity by attenuating acute inflammatory response and minimizing hepatic tissue injury in the non-ablated liver parenchyma. [Copyright &y& Elsevier]

Background: In this experimental study, we investigated the possibility of bacterial translocation, constituting a potential cause of infectious complications, after performing large volume hepatic radiofrequency ablation (RFA). Materials and Methods: Wistar rats were subjected to RFA of the left median liver lobe (approximately 28.5% of the liver volume) after midline laparotomy. At 30min, 24h, 48h, 72h or 1 wk postoperatively, (1) blood samples were collected from the portal and systemic circulation for assessment of endotoxin concentration, (2) tissue specimens were excised from mesenteric lymph nodes, non-ablated liver, pancreas, spleen, kidneys, and lungs for bacterial culture, and (3) segments of terminal ileum were excised for histopathologic examination, morphometric analysis, and apoptotic and mitotic rate estimation. At 1 and 48h, ileal mucosa was collected for oxidative state assessment on the basis of glutathione to glutathione disulfate (GSH/GSSG) ratio. Results: Endotoxin levels were increased in both the portal and systemic circulation. Intestinal bacteria were isolated from all the organs at all time points. Ileal mucosa became gradually atrophic, with a decrease in villous height and density. There was an increase of crypt apoptotic rate, a decrease of GSH/GSSG ratio, while there were only mild signs of inflammation. Conclusions: Large volume liver RFA in the rat resulted to endotoxemia and translocation of intestinal bacteria to proximal and distal to the intestine organs at both the early and late post-RFA periods. The intestinal mucosa barrier was disrupted as suggested by ileal mucosal atrophy, increased crypt apoptosis, and induction of oxidative stress. [Copyright &y& Elsevier]