Chronic stress sensitizes rats to pancreatitis induced by cerulein: Role of TNF-α

Binker, Marcelo Gustavo; Binker-Cosen, Andres A.; Richards, Daniel A.; Gaisano, Herbert Y.; Cosen, Rodica; Cosen-Binker, Laura Iris

doi:10.3748/wjg.v16.i44.5565

Cited by 27 publications

(25 citation statements)

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“…Consistent with our finding, there are reports suggesting that stress can increase tumor growth and tumor marker expression [26,27]. It has also been shown that chronic stress increases susceptibility for developing pancreatitis in rats, which involves TNF-α (tumor necrosis factor-alpha) sensitization of pancreatic acinar cells to undergo injury [28]. However, in contrast to our finding there are studies indicating that chronic stress can strengthen the immune system [15], thereby may cause a resistance to tumorogenesis and forestall against elevating of serum tumor marker levels.…”

Section: Discussionsupporting

confidence: 92%

The Effects of Co-administration of Immobilization Stress and Aloe vera on Serum Carcinoembryonic Antigen in Rats

Ahmadi

Molaei

2015

Zahedan J Res Med Sci

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Background: Immobilization has been used extensively and accepted widely for studying stress-induced alterations. To determine the protective effects of Aloe vera leaf extract, we evaluated the effects of co-administration of immobilization stress and Aloe vera leaf extract on serum level of carcinoembryonic antigen (CEA) tumor marker in male rats. Materials and Methods: In this experimental study, 45 male Wistar rats were randomly divided into 9 groups of 5 rats in each including: 1) control, 2) normal saline receiving, 3) Aloe vera extract receiving, 4) acutely immobilized, 5) chronically immobilized, 6) acutely immobilized+Aloe vera extract, 7) chronically immobilized+Aloe vera extract, 8) acutely immobilized+normal saline and 9) chronically immobilized+normal saline. The animals were exposed to chronic or acute immobilization stress for 2 h/day or 8 h/day for a period of 3 weeks or one week, respectively. Aloe vera extract (300 mg/kg/day) was fed by gavage feeding orally. Blood samples were collected and following serum collection, CEA level was determined by radioimmunoassay method. Data were compared statistically between groups using ANOVA. Results: Serum CEA level was significantly increased in acutely (0.640±0.025 ng/mL) or chronically immobilized (0.647±0.023 ng/mL) rats compared with control animals group (0.564±0.014 ng/mL) (p<0.001). However, there was no significant difference between serum CEA levels of acutely or chronically immobilized Aloe vera extract received animals compared with control rats (0.622±0.027 ng/m and 0.616±0.044 ng/mL, respectively). Conclusion: Our findings indicate that immobilization stress enhances serum CEA level, however, intake of Aloe vera extract can withstand against.

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Section: Discussionsupporting

confidence: 92%

The Effects of Co-administration of Immobilization Stress and Aloe vera on Serum Carcinoembryonic Antigen in Rats

Ahmadi

Molaei

2015

Zahedan J Res Med Sci

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“…Lipase [LPS] is a pancreatic enzyme necessary for the absorption and digestion of nutrients that catalyzes the hydrolysis of glycerol esters of fatty acids. Estimation of LPS is used for diagnosis of pancreatic diseases such as acute and chronic pancreatitis and obstruction of the pancreatic duct [ 29 ]. Increased level of amylase and lipase were observed in the PCBs treated animals.…”

Section: Discussionmentioning

confidence: 99%

Effect of Quercetin on Haematobiochemical and Histological Changes in the Liver of Polychlorined Biphenyls-Induced Adult Male Wistar Rats

Selvakumar

Bavithra

Suganya

et al. 2013

Journal of Biomarkers

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Polychlorinated biphenyls exposure damages the rat liver cells. Hematological parameters such as hemoglobin, packed cell volume, red-blood cells, white-blood cells, neutrophils, platelet counts, and RBC indices were significantly decreased. Polymorphs, eosinophil counts, and erythrocyte sedimentation rate were significantly increased. Serum liver enzymes such as aspartate transaminase, alanine transaminase, alkaline phosphatase, and gamma-glutamyl transferase were increased by PCBs treatment. Serum lipid profiles such as cholesterol, triglycerides, low-density lipoproteins and very-low-density lipoproteins were increased in PCBs-treated rats. High-density lipoprotein, total protein, albumin, globulin levels, and albumin/globulin ratio were also decreased after PCB exposure. Then levels of sodium, potassium, chloride, and bicarbonate were also altered. Serum glucose levels were increased along with total bilirubin after PCBs exposure. Simultaneous quercetin supplementation significantly protected the PCBs-induced changes of hematobiochemical parameters. Thus, quercetin shows a protective role against PCBs-induced alterations in the hematological and biochemical parameters.

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“…This activity consumes high levels of ATP; failure to meet these energy demands can result in protein misfolding and endoplasmic reticulum stress responses. Changes in acinar cell ATP levels have been reported in experimental acute pancreatitis models (20,25), and the extent of ATP depletion in acute pancreatitis may correspond to disease severity (2). Whether such fluctuations in ATP levels influence AMPK activity in acute pancreatitis is unclear.…”

mentioning

confidence: 99%

Cerulein hyperstimulation decreases AMP-activated protein kinase levels at the site of maximal zymogen activation

Shugrue

Alexandre

Villalvilla

et al. 2012

American Journal of Physiology-Gastrointestinal and Liver Physi

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Shugrue CA, Alexandre M, Diaz de Villalvilla A, Kolodecik TR, Young LH, Gorelick FS, Thrower EC. Cerulein hyperstimulation decreases AMP-activated protein kinase levels at the site of maximal zymogen activation. Am J Physiol Gastrointest Liver Physiol 303: G723-G732, 2012. First published July 26, 2012; doi:10.1152/ajpgi.00082.2012.-The premature activation of digestive enzyme zymogens in the pancreatic acinar cell is an important initiating event in acute pancreatitis. We have previously demonstrated that vacuolar ATPase (vATPase) activity is required for zymogen activation. Adenosine monophosphate-activated protein kinase (AMPK) regulates vATPase function in kidney and epididymal clear cells. To determine whether AMPK could affect pancreatitis responses, its effects were first examined in a cellular model of pancreatitis, cerulein-hyperstimulated (100 nM) pancreatic acini. This treatment caused a prominent increase in trypsin and chymotrypsin activities. Pretreatment with AICAR or metformin (AMPK activators) or compound C (an AMPK inhibitor) reduced or increased cerulein-induced zymogen activation, respectively. The association of the vATPase E subunit with membranes, a marker of its activation, tended to be inversely related to AMPK activity (assessed by AICAR and compound C treatments). Cerulein treatment did not change AMPK (␣ and ␤) levels but did lead to an increase in its activation (phosphorylation of Thr172) and induced the time-dependent translocation of the enzyme to a Triton-insoluble compartment. Basal in vivo studies showed that AMPK was widely distributed between membrane and soluble fractions generated by differential centrifugation. After cerulein hyperstimulation, AMPK levels selectively decreased in fractions containing the highest levels of active zymogens. These studies suggest that AMPK activity has a protective role in the pancreatic acinar cell that inhibits zymogen activation in the basal state, and this AMPK effect is reduced during pancreatitis. Therapies that prevent the selective reduction of AMPK in compartments that support zymogen activation could reduce injury during pancreatitis. pancreatic acini; vacuolar ATPase THE PANCREATIC ACINAR CELL comprises over 90% of the exocrine pancreas and synthesizes and secretes the enzymes needed to digest nutrients. Many of the digestive enzymes are stored in the acinar cells as inactive zymogens that become activated only after reaching the small intestine. Premature activation of these zymogens within acinar cells appears to have a critical role in initiating acute pancreatitis (17). Experimental models of acute pancreatitis have been developed in which isolated acinar cells or whole animals are treated with supraphysiological concentrations of cerulein (an orthologue of the hormone cholecystokinin) to induce the early stages of the disease.AMP-activated kinase (AMPK) is a heterotrimeric serine/ threonine kinase, composed of ␣-, ␤-, and ␥-subunits, with the ␣-subunit possessing the catalytic kinase domain. Phosphorylation of the Thr172 resid...

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Chronic stress sensitizes rats to pancreatitis induced by cerulein: Role of TNF-α

Abstract: In rats, chronic stress increases susceptibility for developing pancreatitis, which involves TNF-α sensitization of pancreatic acinar cells to undergo injury by physiological cerulein stimulation.

Cited by 27 publications

References 54 publications

The Effects of Co-administration of Immobilization Stress and Aloe vera on Serum Carcinoembryonic Antigen in Rats

The Effects of Co-administration of Immobilization Stress and Aloe vera on Serum Carcinoembryonic Antigen in Rats

Effect of Quercetin on Haematobiochemical and Histological Changes in the Liver of Polychlorined Biphenyls-Induced Adult Male Wistar Rats

Cerulein hyperstimulation decreases AMP-activated protein kinase levels at the site of maximal zymogen activation

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