Histopathological Changes In Pancreas Research Articles

Glycyrrhizin suppresses the expressions of HMGB1 and relieves the severity of traumatic pancreatitis in rats.

BackgroundHigh mobility group box 1 (HMGB1) plays important roles in a large variety of diseases; glycyrrhizin (GL) is recognized as an HMGB1 inhibitor. However, few studies have focused on whether glycyrrhizin can potentially improve the outcome of traumatic pancreatitis (TP) by inhibiting HMGB1.MethodsA total of 60 male Wistar rats were randomly divided into three groups (n = 20 in each): Control group, TP group and TP-GL group. Pancreatic trauma was established with a custom-made biological impact machine-III, and GL was administered at 15 minutes after the accomplishment of operation. To determine survival rates during the first 7 days after injury, another 60 rats (n = 20 in each) were grouped and treated as mentioned above. At 24 hours of induction of TP, the histopathological changes in pancreas were evaluated and serum amylase levels were tested. Serum tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and HMGB1 were measured using enzyme linked immunosorbent assay. HMGB1 expressions in pancreas were measured using immunohistochemical staining, Western blot and Real-Time PCR analysis.ResultsSerum levels of HMGB1, TNF-α and IL-6 were increased dramatically in TP group at 24 hours after induction of TP. However, these indicators were reduced significantly by GL administration in TP-GL group comparing with TP group (P<0.05). Meanwhile, survival analysis showed that the seven-day survival rate in TP-GL group was significantly higher than that in TP group (85% versus 65%, P<0.05). GL treatment significantly decreased the pancreatic protein and mRNA expressions of HMGB1 and ameliorated the pancreatic injury in rats with TP.ConclusionsGlycyrrhizin might play an important role in improving survival rates and ameliorating pancreatic injury of TP by suppression of the expressions of HMGB1 and other proinflammatory cytokine.

Transforming growth factor (TGF)-β-induced microRNA-216a promotes acute pancreatitis via Akt and TGF-β pathway in mice.

Both transforming growth factor β (TGF-β) and MicroRNA-216a (miR-216a) were reported to be upregulated during acute pancreatitis (AP). Moreover, miR-216a can be induced by TGF-β. This study aimed to investigate how TGF-β and miR-216a involved in the pathogenesis of AP both in a mouse model and in rat pancreatic acinar AR42J cells. Cerulein-induced AP mouse model was established and pretreated with a TGF-β inhibitor, SB431542. Serum amylase, lipase, tumor necrosis factor (TNF)-α, interleukin 6 (IL-6), TGF-β and histopathological changes of pancreas were determined. Expression of miR-216a was detected by quantitative real-time RT-PCR. Bioinformatics was utilized to predict the targets of miR-216a. Expression levels of phosphatase and tensin homolog (PTEN), mothers against decapentaplegic homolog 7 (Smad7), TGF-β receptor I, total Akt and pAkt were detected by Western blot. SB431542 significantly decreased serum amylase, lipase, TNF-α, IL-6, TGF-β, histopathological changes of pancreas and expression of miR-216a in cerulein-induced mouse (P < 0.05). TGF-β induced miR-216a in AR42J cells. PTEN and Smad7 were identified to be the possible targets of miR-216a. Transfection of miR-216a mimics (or inhibitors) in AR42J cells downregulated (or upregulated) the expression of PTEN and Smad7, thus affected the expression of downstream pAkt and TGF-β receptor I. The expression changes of these protein caused by miR-216a can be regulated by SB431542 both in mouse model and AR42J cells. TGF-β promotes AP by inducing miR-216a targeting PTEN and Smad7, thus through PI3K/Akt and TGF-β feedback pathway.

Antidiabetic activities of oligosaccharides of Ophiopogonis japonicus in experimental type 2 diabetic rats

The aim of the present study is to investigate the antidiabetic properties of oligosaccharides of Ophiopogonis japonicus (OOJ) in experimental type 2 diabetic rats. OOJ was administered orally in doses of 225 and 450mg/kg body weight to high-fat diet and low-dose streptozotocin (STZ)-induced type 2 diabetic rats for 3 weeks. The results showed that OOJ treatment could increase body weight, decrease organ related weights of liver and kidney, reduce fasting blood glucose level, and improve oral glucose tolerance in diabetic rats. Moreover, increased glycogen content in liver and skeletal muscle, reduced urinary protein excretion, higher hepatic GCK enzyme activity, lower hepatic PEPCK enzyme activity, enhanced GLP-1 level, decreased glucagon level and alleviated histopathological changes of pancreas occurred in OOJ-treated diabetic rats by comparison with untreated diabetic rats. This study demonstrates, for the first time to our knowledge, that OOJ exerts remarkable antidiabetic effect in experimental type 2 diabetes mellitus, thus justifying its traditional usage.

Histopathological Lesions in the Pancreas of a Rat Model of Diabetes Induced with Complete Freund's Adjuvant and Low-Dose Streptozotocin*)

Neither injection of complete Freund's adjuvant (CFA) alone nor the administration of low doses of streptozotocin (STZ) to rats produced remarkable histopathological changes in the endocrine pancreas, but treatment with the combination of both resulted in necrosis of beta cells. When the combination of CFA/STZ was given two times, necrosis progressed, and the beta cell reserve was depleted to such an extend that persistent hyperglycemia ensued. These changes were associated with a significant reduction in the apparent islet size. A single injection of CFA induced pancreatitis and inflammatory lesions in the exocrine parenchyma with no insular involvement. Three injections caused extensive destruction of pancreatic acinar tissue but only moderate beta cell injury in the minority of islets. Apart from mild degranulation of beta cells, treatment with STZ did not produce histopathological changes in the pancreas. These results suggest that the acute inflammatory process induced by CFA may initially damage the beta cells, increasing thereby their susceptibility to the action of STZ.

Effects of methylprednisolone on neurocyte apoptosis in rats with severe acute pancrcatitis

Objective To investigate the effects of methylprednisolone on neurocyte apoptosis in rats with severe acute pancreatitis(SAP).Methods Thirty-six SD rats were divided into sham operation group,SAP group and methylprednisolone group(12 rats in each group).SAP model was constructed by injecting 5%sodium taurodeoxycholate into biliary-pancreatic duct.Serum amylase,interleukin-6(IL-6),tumor necrosis factor α (TNF-α),volume of aseites and histopathological changes of pancreas were determined.The mRNA expressions of Bcl-2 and Bax in brain tissue were analyzed by RT-PCR.and neuroeyte apoptosis was detected by TUNEL method.Results The levels of serum IL-6 and TNF-α were significantly increased:the expression of Bcl-2 mRNA in brain tissue was down-regulated;the expression of Bax mRNA was up-regulated;the Bcl-2/Bax ratio Was decreased:the apoptosis of the neurocytes was increased in SAP group.Compared with SAP group,the levels of serum IL-6 and TNF-α were significantly decreased;the expression of Bcl-2 mRNA was unchanged but the expression of Bax mRNA was down-regulated in brain tissue,so the Bcl-2/Bax ratio was elevated significantly;the rate of the ueurocyte apoptosis in brain tissue were reduced in methylprednisolone group.Conclusions The apoptosis of neurocytes in brain tissue may be one of the factors causing pancreatic encephalopathy.Methylprednisoione can inhibit the release of IL-6 and TNF-α.improve the balance of Bcl-2 and Bax expression and decrease the apoptosis of neurocytes in brain tissue. Key words: Panereatitis,acute; Methylprednisolone; Apoptosis; Neurocyte

Blocking of monocyte chemoattractant protein-1 (MCP-1) activity attenuates the severity of acute pancreatitis in rats

Monocyte chemoattractant protein-1 (MCP-1) has been shown to affect the progression of various inflammatory disorders, including pancreatitis. To investigate the role of MCP-1 in acute pancreatitis and to seek possible therapeutic means, we evaluated the effect of a plasmid expression vector containing a dominant-negative mutant MCP-1 gene (mMCP-1). Two rat models of acute pancreatitis were employed that used either cerulein (for mild pancreatitis) or a mixture of 5% taurocholic acid and trypsin (for severe pancreatitis). At 6 h after induction of acute pancreatitis with or without injection of mMCP-1, serum amylase levels and cytokine levels, as well as morphological evaluation of the pancreas, were determined. Survival rates were also evaluated. Severe pancreatitis was significantly reduced by mMCP-1 injection. mMCP-1 decreased serum levels of amylase, IL-6, IL-10, and LDH, and improved the survival rate 48 h after disease onset. Histopathological changes of pancreas and lungs were also improved by mMCP-1. MCP-1 appears to be involved in the progression of severe forms of acute pancreatitis. Our data suggested that MCP-1 is a candidate as a therapeutic target to treat acute pancreatitis.

Therapeutic treatment with poly(ADP‐ribose) polymerase inhibitors attenuates the severity of acute pancreatitis and associated liver and lung injury

The mortality associated with acute pancreatitis (AP) is largely attributable to abnormalities that occur in distant organs and supportive care remains the only treatment for patients with these complications. Recently, prophylactic pharmacological blockade of poly(ADP-ribose) polymerase (PARP) enzymes has been shown to attenuate the severity of the disease. However, the clinical relevance of PARP inhibitors administered after the onset of AP remains uncertain. The aim of the present study was to investigate the therapeutic effects of PARP inhibitors in established AP. Mice were fed a choline/methionine-deficient/ethionine-supplemented (CMDE) diet to induce AP. PARP inhibitors were given at 36 h after the onset of CMDE diet. Severity of pancreatitis was assessed by measurements of serum amylase, lipase, IL-1beta and IL-6, and histological grading. Serum hepatic enzymes, myeloperoxidase (MPO) activity and morphological changes were measured as indicators of hepatic insult. Lung injury was evaluated by MPO activity and morphological changes. Survival rates of mice were monitored for 7 days. CMDE diet administration resulted in a significant increase in serum amylase, lipase, IL-1beta, IL-6, alanine aminotransferase and aspartate aminotranferase levels, indicating AP and associated liver injury. Analysis of the histopathological changes in pancreas, liver and lung revealed extensive tissue damage. Treatment of mice with PARP-inhibitors after the onset of AP was associated with a reduction in the severity of AP and, accordingly, with a reduced mortality rate. Our results support the therapeutic application of PARP inhibitors in the treatment of established AP.

Attenuation of streptozotocin mediated oxidative stress, hyperglycemia and toxicity in rats by treatment with B-20 drpos - a homoeopathic preparation

The present study is aimed at finding the effect of B-20 drops, a homoeopathic formulation, in streptozotocin (STZ) induced diabetic rats. B-20 drops comprises of the constituents derived from plants and other natural sources, and are generally prescribed by the homoeopathic physician, in cases of hyperglycemia and diabetes. The elevated levels of fasting blood glucose and pancreatic lipid peroxides observed in rats treated with STZ were significantly reduced by the treatment of B-20 drops. The reduced liver glycogen contents were also brought back to near normal level by B-20 drops treatment in STZ diabetic rats. STZ induced histopathological changes in pancreas and liver was also partially reversed by B-20 drops. The findings indicate that B-20 drops help in improving the glycogen stores in the liver and prevents STZ induced damage through free radicals by decreasing the pancreatic lipid peroxides levels.

Effects of diazinon at different doses on rat liver and pancreas tissues

Diazinon is one of the most widely used organophosphates in agriculture. Toxic effects of diazinon are due to the inhibition of acetylcholinesterase, an enzyme needed for proper nervous system function. This study was designed to investigate the effects of diazinon at different doses on pancreas and liver tissues and in which dose level diazinon shows its effects. Sixty male Wistar albino rats were included in this study. Animals were initially divided into control and diazinon given groups. There were 10 animals in the control group and 50 animals in diazinon administered group. The latter was divided into five equal subgroups: 25, 50, 100, 200 and 300 mg/kg of diazinon administered groups. Control group was given only saline. All animals in 300 mg/kg diazinon group died. After 24 h, rats were sacrificed under ether anesthesia. Tissue and blood samples were taken for biochemical and histopathological analysis. Sample tissues were examined under light microscope. In biochemical analysis, AST, ALT, LDH, amylase and lipase enzyme activities were measured. One-way ANOVA test was used to compare the groups. In 200 mg/kg diazinon given group, it has been observed some histopathological changes in pancreas and liver tissues. Cholinesterase activities were significantly decreased and alkaline phosphatase levels were increased in all diazinon given groups, when compared with the controls. There was statistically significant difference between the control and diazinon given groups by means of serum amylase, lipase, ALT and AST activities ( p < 0.05). LDH activities were significantly increased in 100 and 200 mg diazinon given groups, when compared with the controls ( p < 0.05). Histopathological changes were observed only in 200 mg diazinon given group. This evidence suggest that diazinon effect is dose dependent and this is possibly 10–15% of the LD 50 dose (200 mg/kg), which cause acute pancreatitis and histopathological changes in liver.

Effects of Chinese herbal medicines on spontaneous chronic pancreatitis in rats and the pathological relationships between formulas and syndromes

To investigate the effects of Guizhi Decoction, Chaihu Guizhi Decoction, Xiaochaihu Decoction and camostat on rat spontaneous chronic pancreatitis and the pathological relationships between formulas and syndromes. Fifty-seven male WBN/Kob rats at age of 4 weeks were divided into five groups: untreated group (n=18), Guizhi Decoction-treated group (n=9), Chaihu Guizhi Decoction-treated group (n=9), Xiaochaihu Decoction-treated group (n=9) and camostat-treated group (n=12). The rats in each group were fed with corresponding drugs for 12 weeks. The pancreatic wet weight and histopathological changes of pancreatic tissue were observed every four weeks. Meanwhile, the expression level of pancreatitis-associated protein (PAP) in pancreas was detected by RT-PCR technique and immunohistochemical method. In the untreated group, the histopathological changes in pancreas were observed in rats at 12-week age, while such changes were absent in the Guizhi Decoction-treated group. The histopathological changes in pancreas were quite remarkable in rats at 16-week age in both the Xiaochaihu Decoction-treated and the camostat-treated groups. The expression level of PAP mRNA was lower in the Guizhi Decoction-treated group than those in the other groups. The PAP expressions were absent in rats at 12-week age in the Guizhi Decoction-treated and the Chaihu Guizhi Decocion-treated groups. Guizhi Decoction, Chaihu Guizhi Decoction, Xiaochaihu Decoction and camostat are all beneficial to prevention and cure of chronic pancreatitis, and Guizhi Decoction is the most effective one. It is speculated that Taiyang exterior syndrome may be the pathogenesis of basic syndrome may be the pathogenesis of basic syndrome of spontaneous chronic pancreatitis, and the expression of PAP may be its pathological basis.

Anti-diabetic Activity of SMK001, a Poly Herbal Formula in Streptozotocin Induced Diabetic Rats: Therapeutic Study

The therapeutic anti-diabetic effect of SMK001, a poly herbal formula was evaluated in the streptozotocin (STZ; 60 mg/kg, single intraperitoneal injection) induced diabetic rats. For therapeutic study, test articles were orally dosed once a day from 21 d after STZ-dosing at 100, 200 and 500 mg/kg/5 ml dosage levels for 4 weeks. The body weight changes, blood and urine glucose level changes were monitored with changes on the pancreas weight, and after sacrifice, the histopathological changes of pancreas and the changes of insulin- and glucagon-producing cells were also observed by immunohistochemistry. The results were compared to that of glibenclamide 5 mg/kg-dosing group. Significantly (p<0.01 or p<0.05) decrease of body weight, blood and urine glucose levels were detected in STZ-induced diabetic animals with disruption and disappearance of pancreatic islets. In addition, significantly (p<0.01) increase of glucagon- and decrease of insulin-producing cells were detected in STZ induced diabetic rats. However, these diabetic changes were significantly (p<0.01 or p<0.05) and dose dependently decreased in SMK001-dosing groups, and SMK001 100 mg/kg showed more favorable effects compared to that of glibenclamide 5 mg/kg. Based on these results, it is considered that SMK001 has favorable effect to inhibit the changes on the blood and urine glucose levels, body weight and the histopathological changes of pancreas in STZ induce diabetes.

Effect of hydrogen peroxide on permeability of the main pancreatic duct and morphology of the pancreas

Background: The direct effect of free oxygen radicals, if any, on the morphology of the pancreas has never been studied in vivo. This study was designed to evaluate the effects of hydrogen peroxide (H 2O 2) on permeability of the main pancreatic duct (MPD) and morphology of pancreas in cats when administered intraductally or intraarterially. Methods: Thirty-six mongrel cats were randomly allocated into three groups, and all groups were divided into two subgroups. In group I and III, MPD was perfused with either standard perfusate (group IA and IIIA) or H 2O 2 at a concentration of 150 μM (group IB and IIIB) for 3 hours. In group II, the splenic artery was infused either with 0.9% sodium chloride (group IIA) or H 2O 2 (group IIB) for 3 hours. After 3 hours, in group I and II, MPD was perfused with 99mTc labelled dextran, and the percentage of the dextran permeated from the MPD into the portal vein was calculated for the evaluation of the pancreatic duct permeability. Then, tissue samples were obtained for the examination of early histopathological changes in pancreas. In group III, following ductal perfusion studies, the cats were allowed to recover. After 24 hours animals were killed, and samples were taken for the examination of late histological changes in pancreas. In all groups, an inflammatory score was created for each animal based on the pathological changes in pancreas: edema, leukocyte infiltration, parenchymal necrosis, and hemorrhage. Results: Group I: All cats developed acute edematous pancreatitis with significantly higher inflammatory scores than controls ( P <0.01). Desquamation of the single layer of columnar epithelium that normally lined the duct and leukocyte infiltration around the MPD duct were found. Pancreatic duct permeability was found to be increased significantly ( P <0.01). Group II: There were no statistical differences in inflammatory scores and pancreatic duct permeability between experimental and control groups ( P >0.05). Group III: All animals developed gross acute edematous pancreatitis after 3 hours of intraductal H 2O 2 perfusion. Histopathological changes at 24 hours were much more pronounced in group IIIB than in group IIIA including focal necrosis and hydropic degeneration of acinar cells. Conclusion: This study has shown that intraductal H 2O 2 perfusion induced acute edematous pancreatitis with marked histopathological changes and increased pancreatic duct permeability in cats. Intraarterial H 2O 2 infusion, however, has no effect on the permeability of the MPD and morphology of pancreas in our model.