Counter effects of Vitamin E against Outcomes of Alcohol Toxicity in Pancreatic Acini: Histomorphometric Study

2021 ◽  
Vol 15 (11) ◽  
pp. 2974-2978
Author(s):  
Noman Ullah Wazir ◽  
Jehanzeb Khan ◽  
Zilli Huma ◽  
Farooq Khan ◽  
Nighat Ara ◽  
...  
Keyword(s):  
Vitamin E ◽  
Normal Saline ◽  
Serum Amylase ◽  
Acinar Cells ◽  
Protective Role ◽  
Ethanol Solution ◽  
Pancreatic Acinar Cells ◽  
Pancreatic Acini ◽  
Short Period ◽  
Experimental Group

Aim: To evaluate the effects of alcohol on the microscopic morphology of the exocrine pancreas and blood serum amylase and to explored that if vitamin E has a protective role against alcohol-induced damage in the pancreas of rabbits. Study design: Analytical experimental study Place and duration of study: Departments of Anatomy, Pathology and Pharmacology in Peshawar Medical College Pakistan from 1st January 2019 to 30th June 2019. Methodology: Eighteen healthy adult male domestic rabbits weighing 1-1.5 kg were chosen (oryctolaguscuniculus). The control group A received proper food and normal saline as drinking water, experimental group B received proper diet and 30 percent ethanol solution (30ml/kg/day) orally daily with normal saline, and experimental group C received proper diet, 30 percent ethanol solution (30ml/kg/day), vitamin E (50mg/kg/day) orally daily with normal saline. Each rabbit's blood was taken for serum amylase. Morphology of acinar cells included: 1) number of cells, (10 acini/field, 2) size of acini, 3) size of acinar cells, and 4) size of acinar nuclei. Results: Normal value of serum amylase in rabbits was found. The difference in serum amylase levels between the control and experimental groups for both E4 and E8 animals was not statistically significant. There was no significant difference in the number of pancreatic acinar cells, size of pancreatic acini, the pancreatic acinar cell size, and pancreatic acinar cells nuclear size in the control and experimental groups for both E4 and E8 animals. Conclusion: Alcohol consumption had no influence on the histomorphology of the rabbits' pancreatic acini in a short period (4-8 weeks). No significant variation was noted in the pancreatic acinar cells count & size, pancreatic acinar cells nuclear count and size, and pancreatic acini size. Therefore, protective role of vitamin E was not usefully identified. Keywords: Alcohol, Pancreas, Histomorphology, Vitamin E, Serum amylase

Hepatocytes Protection by Vitamin E in Alcoholic Liver Injury: A Light Microscopic Study

2021 ◽  
Vol 15 (10) ◽  
pp. 2869-2874
Author(s):  
Noman Ullah Wazir ◽  
Muhammad Saeed ◽  
Ihsan Ullah Wazir ◽  
Jehanzeb Khan ◽  
Fida Ullah Wazir ◽  
...  
Keyword(s):  
Drinking Water ◽  
Vitamin E ◽  
Normal Saline ◽  
Protective Role ◽  
Ethanol Solution ◽  
Keywords Alcohol ◽  
Short Period ◽  
Histomorphological Changes ◽  
Group B ◽  
Experimental Group

Background: Alcohol induces histomorphological changes in the liver and vitamin E has a protective role against these changes. Objective: To observe changes in hepatocytes of rabbits exposed to intragastric administration of alcohol and the protective role of vitamin E against these changes. Study Design: Analytical experimental study Place and Duration of Study: Department of Anatomy, Pathology and Pharmacology of Peshawar Medical College, Peshawar, Pakistan from 1st January 2016 to 30th June 2016. Methodology: Eighteen male rabbits domestic type (Oryctolaguscuniculus) were included. Experimental duration for category E8 animals was 8 weeks while for category E4 animals it was 4 weeks. The groups were, control group A in which animals were given proper food and normal saline as drinking water, experimental group B in which animals were fed on proper diet and 30% ethanol solution (30 ml/kg/day) orally daily with normal saline and experimental group C in which animals were treated with proper diet, 30% ethanol solution (30 ml/kg/day), vitamin E (50 mg/kg/day) orally daily and normal saline as drinking water. Results: The difference in the ALT, hepatocyte count and size and hepatocyte nuclear count and size of control and experimental groups and experimental group B-II and C-II from both category E4 and E8 showed a highly significant P values. Conclusion: Alcohol causes histomorphological changes in the liver even in the short period of 4-8 weeks and these changes can be minimized by the antioxidant action of vitamin E. Keywords: Alcohol, Liver, Histomorphology, Vitamin E, Hepatocyte, ALT

Ethanol sensitizes NF-κB activation in pancreatic acinar cells through effects on protein kinase C-ε

2006 ◽  
Vol 291 (3) ◽  
pp. G432-G438 ◽  
Author(s):  
Akihiko Satoh ◽  
Anna S. Gukovskaya ◽  
Joseph R. Reeve ◽  
Tooru Shimosegawa ◽  
Stephen J. Pandol
Keyword(s):  
Acinar Cells ◽  
Pancreatic Acinar Cells ◽  
High Dose ◽  
Pancreatic Acini ◽  
Kinase C ◽  
Pkc Isoforms ◽  
Ethanol Abuse ◽  
Pkc Ζ ◽  
Sensitizing Effect

Although ethanol abuse is the most common cause of pancreatitis, the mechanism of alcohol's effect on the pancreas is not well understood. Previously, we demonstrated that in vitro ethanol treatment of pancreatic acinar cells augmented the CCK-8-induced activation of NF-κB, a key signaling system involved in the inflammatory response of pancreatitis. In the present study, we determine the role for individual PKC isoforms in the sensitizing effect of ethanol on NF-κB activation. Dispersed rat pancreatic acini were treated with and without ethanol and then stimulated with CCK-8; 100 nM CCK-8 caused both NF-κB and PKC-δ, -ε, and -ζ activation, whereas 0.1 nM CCK-8 did not increase PKC-ε, PKC-ζ, or NF-κB activity. CCK-8 (0.1 nM) did activate PKC-δ. PKC-ε activator alone did not cause NF-κB activation; however, together with 0.1 nM CCK-8, it caused NF-κB activation. Ethanol activated PKC-ε without affecting other PKC isoforms or NF-κB activity. Of note, stimulation of acini with ethanol and 0.1 nM CCK-8 resulted in the activation of PKC-δ, PKC-ε, and NF-κB. The NF-κB activation to 0.1 nM CCK-8 in ethanol-pretreated acini was inhibited by both PKC-δ inhibitor and PKC-ε inhibitor. Taken together, these results demonstrate the different modes of activation of PKC isoforms and NF-κB in acini stimulated with ethanol, high-dose CCK-8, and low-dose CCK-8, and furthermore suggest that activation of both PKC-ε and -δ is required for NF-κB activation. These results suggest that ethanol enhances the CCK-8-induced NF-κB activation at least in part through its effects on PKC-ε.

Transport and interaction of nitrogen oxides and NO2 with CO2-HCO3- transporters in pancreatic acini

1994 ◽  
Vol 267 (2) ◽  
pp. C385-C393 ◽  
Author(s):  
H. Zhao ◽  
X. Xu ◽  
K. Ujiie ◽  
R. A. Star ◽  
S. Muallem
Keyword(s):  
Nitric Oxide ◽  
Nitrogen Oxides ◽  
Acinar Cells ◽  
Cellular Proteins ◽  
Pancreatic Acinar Cells ◽  
Disulfonic Acid ◽  
No Production ◽  
Pancreatic Acini ◽  
Cytosolic Acidification ◽  
Stimulation Of

Recently, we showed that NO2- increases gap junction (GJ) permeability and synchronizes intracellular Ca2+ concentration oscillations in pancreatic acini (Loessburg et al., J. Biol. Chem. 268: 19769-19775, 1993). NO2- is also an end product of nitric oxide (NO) production and metabolism. Because of the effect of NO2- on GJ permeability and the possible importance of NO2- in NO metabolism and cytotoxicity, we used pancreatic acinar cells and intracellular pH (pHi) measurements to study the interaction of nitrogen oxides and NO2- with cellular proteins. Exposing cells to NO2- resulted in a concentration-dependent cytosolic acidification. The acidification did not require the transport of NO2- and was not mediated by diffusion of HNO2. Because the acidification was prevented by CO2-HCO3- and inhibition of carbonic anhydrase, it is possible that other nitrogen oxides present in a solution containing NO2- enter the cells by diffusion and interact with OH- or H2O to stably acidify the cytosol. NO2- itself is shown to be transported by the HCO3- transporters present in the plasma membrane. Thus manipulation of the cellular Cl- gradient and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) were used to show Cl-/NO2- exchange, whereas stimulation of external Na(+)-dependent amiloride-insensitive and DIDS-sensitive pHi increase in acidified cells was used to demonstrate a Na(+)-(NO2-)n cotransport. Hence NO2- can be a convenient substitute for HCO3- when studying HCO3- transport in an open system. The studies also show that cellular levels of nitrogen oxides and NO2- can be modulated by the cellular HCO3(-)-buffering system.(ABSTRACT TRUNCATED AT 250 WORDS)

Crambene induces pancreatic acinar cell apoptosis via the activation of mitochondrial pathway

2006 ◽  
Vol 291 (1) ◽  
pp. G95-G101 ◽  
Author(s):  
Yang Cao ◽  
Sharmila Adhikari ◽  
Abel Damien Ang ◽  
Marie Véronique Clément ◽  
Matthew Wallig ◽  
...  
Keyword(s):  
Acinar Cell ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Fas Ligand ◽  
Annexin V ◽  
Acinar Cells ◽  
Mitochondrial Pathway ◽  
Pancreatic Acinar Cell ◽  
Pancreatic Acinar Cells ◽  
Pancreatic Acini

We investigated the apoptotic pathway activated by crambene (1-cyano-2-hydroxy-3-butene), a plant nitrile, on pancreatic acinar cells. As evidenced by annexin V-FITC staining, crambene treatment for 3 h induced the apoptosis but not necrosis of pancreatic acini. Caspase-3, -8, and -9 activities in acini treated with crambene were significantly higher than in untreated acini. Treatment with caspase-3, -8, and -9 inhibitors inhibited annexin V staining, as well as caspase-3 activity, pointing to an important role of these caspases in crambene-induced acinar cell apoptosis. The mitochondrial membrane potential was collapsed, and cytochrome c was released from the mitochondria in crambene-treated acini. Neither TNF-α nor Fas ligand levels were changed in pancreatic acinar cells after crambene treatment. These results provide evidence for the induction of pancreatic acinar cell apoptosis in vitro by crambene and suggest the involvement of mitochondrial pathway in pancreatic acinar cell apoptosis.

CRHSP-24 phosphorylation is regulated by multiple signaling pathways in pancreatic acinar cells

2003 ◽  
Vol 285 (4) ◽  
pp. G726-G734 ◽  
Author(s):  
Claus Schäfer ◽  
Hanna Steffen ◽  
Karen J. Krzykowski ◽  
Burkhard Göke ◽  
Guy E. Groblewski
Keyword(s):  
Signaling Pathways ◽  
Acinar Cells ◽  
Pancreatic Acinar Cells ◽  
Dependent Manner ◽  
Calyculin A ◽  
Concentration Dependent Manner ◽  
Pancreatic Acini ◽  
Heat Stable ◽  
Heat Stable Protein ◽  
Mrna Binding

Ca2+-regulated heat-stable protein of 24 kDa (CRHSP-24) is a serine phosphoprotein originally identified as a physiological substrate for the Ca2+-calmodulin regulated protein phosphatase calcineurin (PP2B). CRHSP-24 is a paralog of the brain-specific mRNA-binding protein PIPPin and was recently shown to interact with the STYX/dead phosphatase protein in developing spermatids (Wishart MJ and Dixon JE. Proc Natl Acad Sci USA 99: 2112–2117, 2002). Investigation of the effects of phorbol ester (12- o-tetradecanoylphorbol-13-acetate; TPA) and cAMP analogs in 32P-labeled pancreatic acini revealed that these agents acutely dephosphorylated CRHSP-24 by a Ca2+-independent mechanism. Indeed, cAMP- and TPA-mediated dephosphorylation of CRHSP-24 was fully inhibited by the PP1/PP2A inhibitor calyculin A, indicating that the protein is regulated by an additional phosphatase other than PP2B. Supporting this, CRHSP-24 dephosphorylation in response to the Ca2+-mobilizing hormone cholecystokinin was differentially inhibited by calyculin A and the PP2B-selective inhibitor cyclosporin A. Stimulation of acini with secretin, a secretagogue that signals through the cAMP pathway in acini, induced CRHSP-24 dephosphorylation in a concentration-dependent manner. Isoelectric focusing and immunoblotting indicated that elevated cellular Ca2+ dephosphorylated CRHSP-24 on at least three serine sites, whereas cAMP and TPA partially dephosphorylated the protein on at least two sites. The cAMP-mediated dephosphorylation of CRHSP-24 was inhibited by low concentrations of okadaic acid (10 nM) and fostriecin (1 μM), suggesting that CRHSP-24 is regulated by PP2A or PP4. Collectively, these data indicate that CRHSP-24 is regulated by diverse and physiologically relevant signaling pathways in acinar cells, including Ca2+, cAMP, and diacylglycerol.

scholarly journals Regulation of transforming growth factor β-induced responses by protein kinase A in pancreatic acinar cells

2008 ◽  
Vol 295 (1) ◽  
pp. G170-G178 ◽  
Author(s):  
Huibin Yang ◽  
Cheong J. Lee ◽  
Lizhi Zhang ◽  
Maria Dolors Sans ◽  
Diane M. Simeone
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Transforming Growth Factor ◽  
Acinar Cells ◽  
Lung Epithelial Cells ◽  
Pancreatic Acinar Cells ◽  
Intracellular Camp ◽  
Physical Interaction ◽  
Pancreatic Acini ◽  
Kinase A

TGF-β is an important regulator of growth and differentiation in the pancreas and has been implicated in pancreatic tumorigenesis. We have recently demonstrated that TGF-β can activate protein kinase A (PKA) in mink lung epithelial cells (Zhang L, Duan C, Binkley C, Li G, Uhler M, Logsdon C, Simeone D. Mol Cell Biol 24: 2169–2180, 2004). In this study, we sought to determine whether TGF-β activates PKA in pancreatic acinar cells, the mechanism by which PKA is activated, and PKA's role in TGF-β-mediated growth regulatory responses. TGF-β rapidly activated PKA in pancreatic acini while having no effect on intracellular cAMP levels. Coimmunoprecipitation experiments demonstrated a physical interaction between a Smad3/Smad4 complex and the regulatory subunits of PKA. TGF-β also induced activation of the PKA-dependent transcription factor CREB. Both the specific PKA inhibitor H89 and PKI peptide significantly blocked TGF-β's ability to activate PKA and CREB. TGF-β-mediated growth inhibition and TGF-β-induced p21 and SnoN expression in pancreatic acinar cells were blocked by H89 and PKI peptide. This study demonstrates that this novel cross talk between TGF-β and PKA signaling pathways may play an important role in regulating TGF-β signaling in the pancreas.

Multiple isoforms of the ryanodine receptor are expressed in rat pancreatic acinar cells

2000 ◽  
Vol 351 (1) ◽  
pp. 265-271 ◽  
Author(s):  
Timothy J. FITZSIMMONS ◽  
Ilya GUKOVSKY ◽  
James A. McROBERTS ◽  
Edward RODRIGUEZ ◽  
F. Anthony LAI ◽  
...  
Keyword(s):  
Western Blot ◽  
Ryanodine Receptor ◽  
Acinar Cell ◽  
Acinar Cells ◽  
Protein Band ◽  
Pancreatic Acinar Cell ◽  
Pancreatic Acinar Cells ◽  
Rt Pcr ◽  
Pancreatic Acini ◽  
Cell Functions

Regulation of cytosolic Ca2+ is important for a variety of cell functions. The ryanodine receptor (RyR) is a Ca2+ channel that conducts Ca2+ from internal pools to the cytoplasm. To demonstrate the presence of the RyR in the pancreatic acinar cell, we performed reverse transcriptase (RT)-PCR, Western blot, immunocytochemistry and microscopic Ca2+-release measurements on these cells. RT-PCR showed the presence of mRNA for RyR isoforms 1, 2 and 3 in both rat pancreas and dispersed pancreatic acini. Furthermore, mRNA expression for RyR isoforms 1 and 2 was demonstrated by RT-PCR in individual pancreatic acinar cells selected under the microscope. Western-blot analysis of acinar cell immunoprecipitates, using antibodies against RyR1 and RyR2, showed a high-molecular-mass (> 250kDa) protein band that was much less intense when immunoprecipitated in the presence of RyR peptide. Functionally, permeablized acinar cells stimulated with the RyR activator, palmitoyl-CoA, released Ca2+ from both basolateral and apical regions. These data show that pancreatic acinar cells express multiple isoforms of the RyR and that there are functional receptors throughout the cell.

scholarly journals Intracellular divalent cation release in pancreatic acinar cells during stimulus-secretion coupling. II. Subcellular localization of the fluorescent probe chlorotetracycline.

1978 ◽  
Vol 76 (2) ◽  
pp. 386-399 ◽  
Author(s):  
D E Chandler ◽  
J A Williams
Keyword(s):  
Divalent Cation ◽  
Acinar Cells ◽  
Pancreatic Acinar Cells ◽  
Ionophore A23187 ◽  
Pancreatic Acini ◽  
Fluorescent Cell ◽  
Mitochondrial Inhibitors ◽  
Cell Compartments ◽  
Large Numbers ◽  
Stimulus Secretion Coupling

Subcellular distribution of the divalent cation-sensitive probe chlorotetracycline (CTC) was observed by fluorescence microscopy in isolated pancreatic acinar cells, dissociated hepatocytes, rod photoreceptors, and erythrocytes. In each cell type, areas containing membranes fluoresced intensely while areas containing no membranes (nuclei and zymogen granules) were not fluorescent. Cell compartments packed with rough endoplasmic reticulum or Golgi vesicles (acinar cells) or plasma membrane-derived membranes (rod outer segments) exhibited a uniform fluorescence. In contrast, cell compartments having large numbers of mitochondria (hepatocytes and the rod inner segment) exhibited a punctate fluorescence. Punctate fluorescence was prominent in the perinuclear and peri-granular areas of isolated acinar cells during CTC efflux, suggesting that under these conditions mitochondrial fluorescence may account for a large portion of acinar cell fluorescence. Fluorometry of dissociated pancreatic acini, preloaded with CTC, showed that application of the mitochondrial inhibitors antimycin A, NaCN, rotenone, or C1CCP, or of the divalent cation ionophore A23187 (all agents known to release mitochondrial calcium) rapidly decreased the fluorescence of acini. In the case of mitochondrial inhibitors, this response could be elicited before but not following the loss of CTC fluorescence induced by bethanechol stimulation. Removal of extracellular Ca2+ and Mg2+ or addition of EDTA also decreased fluorescence but did not prevent secretagogues or mitochondrial inhibitors from eliciting a further response. These data suggest that bethanechol acts to decrease CTC fluorescence at the same intracellular site as do mitochondrial inhibitors. This could be due to release of calcium from either mitochondria or another organelle that requires ATP to sequester calcium.

scholarly journals Transgenic expression of pancreatic secretory trypsin inhibitor-1 rescues SPINK3-deficient mice and restores a normal pancreatic phenotype

2010 ◽  
Vol 298 (4) ◽  
pp. G518-G524 ◽  
Author(s):  
Joelle M.-J. Romac ◽  
Masaki Ohmuraya ◽  
Cathy Bittner ◽  
M. Faraz Majeed ◽  
Steven R. Vigna ◽  
...  
Keyword(s):  
Trypsin Inhibitor ◽  
Survival Rates ◽  
Acinar Cells ◽  
Threshold Level ◽  
Protective Role ◽  
Trypsin Inhibitors ◽  
Pancreatic Acinar Cells ◽  
Wild Type ◽  
Transgenic Expression ◽  
Pancreatic Trypsin Inhibitor

Endogenous trypsin inhibitors are synthesized, stored, and secreted by pancreatic acinar cells. It is believed that they play a protective role in the pancreas by inhibiting trypsin within the cell should trypsinogen become prematurely activated. Rodent trypsin inhibitors are highly homologous to human serine protease inhibitor Kazal-type 1 (SPINK1). The mouse has one pancreatic trypsin inhibitor known as SPINK3, and the rat has two trypsin inhibitors commonly known as pancreatic secretory trypsin inhibitors I and II (PSTI-I and -II). Rat PSTI-I is a 61-amino acid protein that shares 65% sequence identity with mouse SPINK3. It was recently demonstrated that mice with genetic deletion of the Spink3 gene ( Spink3−/− ) do not survive beyond 15 days and lack normal pancreata because of pancreatic autophagy. We have shown that targeted transgenic expression of the rat Psti1 gene to acinar cells in mice [ TgN(Psti1)] protects mice against caerulein-induced pancreatitis. To determine whether the autophagic phenotype and lethality in Spink3−/− mice were due to lack of pancreatic trypsin inhibitor, we conducted breeding studies with Spink3+/− heterozygous mice and TgN(Psti1) mice. We observed that, whereas Spink3+/+, Spink3+/−, and Spink3−/− /TgN(Psti1) mice had similar survival rates, no Spink3−/− mice survived longer than 1 wk. The level of expression of SPINK3 protein in acini was reduced in heterozygote mice compared with wild-type mice. Furthermore, endogenous trypsin inhibitor capacity was reduced in the pancreas of heterozygote mice compared with wild-type or knockout mice rescued with the rat Psti1 gene. Surprisingly, the lesser amount of SPINK3 present in the pancreata of heterozygote mice did not predispose animals to increased susceptibility to caerulein-induced acute pancreatitis. We propose that a threshold level of expression is sufficient to protect against pancreatitis.

scholarly journals Cholecystokinin octapeptide inhibits Ca2+-dependent amylase secretion from permeabilized pancreatic acini by blocking the MgATP-dependent priming of exocytosis

1998 ◽  
Vol 330 (1) ◽  
pp. 329-334 ◽  
Author(s):  
J. Philip PADFIELD ◽  
Ninder PANESAR
Keyword(s):  
Acinar Cells ◽  
Secretory Response ◽  
Pancreatic Acinar Cells ◽  
Amylase Secretion ◽  
Rapid Phase ◽  
Pancreatic Acini ◽  
Cholecystokinin Octapeptide ◽  
Cholecystokinin Receptor ◽  
Specific Antagonist

At present little is known about how the low-affinity cholecystokinin receptor inhibits secretagogue-stimulated amylase secretion from pancreatic acinar cells. To examine this question we have determined how cholecystokinin octapeptide (CCK8) influences Ca2+-dependent amylase secretion from α-toxin-permeabilized pancreatic acini. CCK8 significantly inhibited Ca2+-stimulated amylase secretion. The inhibitory actions of CCK8 were completely blocked by the addition of JMV-180, a specific antagonist for the low-affinity CCK8 receptor. Previous studies have shown that Ca2+-dependent amylase secretion from α-toxin-permeabilized acini has two distinct phases [Padfield and Panesar (1997) Am. J. Physiol. 36, G655-660]. There is an initial rapid phase of secretion which represents release from exocytotic sites primed by MgATP prior to permeabilization. This is followed by a slower sustained phase of secretion which, in part, reflects the MgATP-dependent repriming of the exocytotic machinery. CCK8 did not influence the initial rapid phase of the Ca2+-dependent secretory response, but inhibited the second slower sustained phase. Moreover, CCK8 was shown to inhibit the MgATP-dependent priming of exocytosis in the acini. These results indicate that the low-affinity CCK receptor blocks stimulated amylase secretion by inhibiting the MgATP-dependent repriming of exocytosis.

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