Suppression of L-Arginine-Induced Acute Necrotizing Pancreatitis in Rats by Metformin Associated with the Inhibition of Myeloperoxidase and Activation of Interleukin-10

SUMMARY: Acute pancreatitis is a frequent life-threatening inflammatory disease of the pancreas characterized by severe abdominal pain that lasts for days to weeks. We sought to determine whether the antidiabetic and anti-inflammatory drug, metformin can substantially protect against acute pancreati...

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Autor principal:	Al-Hashem,Fahaid
Lenguaje:	English
Publicado:	Sociedad Chilena de Anatomía 2021
Materias:	Acute pancreatitis L-arginine Metformin MPO IL-10 Rat model
Acceso en línea:	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0717-95022021000100102
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spelling	oai:scielo:S0717-950220210001001022021-03-01Suppression of L-Arginine-Induced Acute Necrotizing Pancreatitis in Rats by Metformin Associated with the Inhibition of Myeloperoxidase and Activation of Interleukin-10Al-Hashem,Fahaid Acute pancreatitis L-arginine Metformin MPO IL-10 Rat model SUMMARY: Acute pancreatitis is a frequent life-threatening inflammatory disease of the pancreas characterized by severe abdominal pain that lasts for days to weeks. We sought to determine whether the antidiabetic and anti-inflammatory drug, metformin can substantially protect against acute pancreatitis in an animal model of L-arginine-induced acute pancreatitis, and whether this is associated with the augmentation of the anti-inflammatory cytokine interleukin-10 (IL-10) and inhibition of the enzyme that promotes tissue damage, myeloperoxidase (MPO). Rats were either injected with two doses of the amino acid L-arginine (2.5 gm/kg; i.p., at one-hour intervals) before being sacrificed after 48 hours (model group) or were pretreated with metformin (50 mg/kg) daily for two weeks prior to L- arginine injections and continued receiving metformin until the end of the experiment (protective group). Using microscopic examination of the pancreas and blood chemistry, we observed that L-arginine induced acute pancreatic injury. This is demonstrated by an enlarged pancreas with patchy areas of haemorrhage, vacuolated cytoplasm and pyknotic nuclei in the acini, disorganized lobular architecture with infiltration of inflammatory cells within the interlobular connective tissue (CT) septa, and the presence of congested blood vessels that were substantially ameliorated by metformin. Metformin also significantly (p<0.05) inhibited L-arginine-induced MPO, lactate dehydrogenase (LDH), and the inflammatory biomarker tumor necrosis factor alpha (TNF-α). Whereas, metformin significantly (p<0.05) increased IL-10 levels that were inhibited by pancreatitis induction. We further demonstrated a significant (p<0.001) correlation between the scoring of the degree of pancreatic lobules damage tissue damage and the blood levels of TNF-α, IL-10, LDH, and MPO. Thus, metformin effectively protects against L-arginine-induced acute pancreatitis, which is associated with the inhibition of MPO and augmentation of IL-10.info:eu-repo/semantics/openAccessSociedad Chilena de AnatomíaInternational Journal of Morphology v.39 n.1 20212021-02-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0717-95022021000100102en10.4067/S0717-95022021000100102
institution	Scielo Chile
collection	Scielo Chile
language	English
topic	Acute pancreatitis L-arginine Metformin MPO IL-10 Rat model
spellingShingle	Acute pancreatitis L-arginine Metformin MPO IL-10 Rat model Al-Hashem,Fahaid Suppression of L-Arginine-Induced Acute Necrotizing Pancreatitis in Rats by Metformin Associated with the Inhibition of Myeloperoxidase and Activation of Interleukin-10
description	SUMMARY: Acute pancreatitis is a frequent life-threatening inflammatory disease of the pancreas characterized by severe abdominal pain that lasts for days to weeks. We sought to determine whether the antidiabetic and anti-inflammatory drug, metformin can substantially protect against acute pancreatitis in an animal model of L-arginine-induced acute pancreatitis, and whether this is associated with the augmentation of the anti-inflammatory cytokine interleukin-10 (IL-10) and inhibition of the enzyme that promotes tissue damage, myeloperoxidase (MPO). Rats were either injected with two doses of the amino acid L-arginine (2.5 gm/kg; i.p., at one-hour intervals) before being sacrificed after 48 hours (model group) or were pretreated with metformin (50 mg/kg) daily for two weeks prior to L- arginine injections and continued receiving metformin until the end of the experiment (protective group). Using microscopic examination of the pancreas and blood chemistry, we observed that L-arginine induced acute pancreatic injury. This is demonstrated by an enlarged pancreas with patchy areas of haemorrhage, vacuolated cytoplasm and pyknotic nuclei in the acini, disorganized lobular architecture with infiltration of inflammatory cells within the interlobular connective tissue (CT) septa, and the presence of congested blood vessels that were substantially ameliorated by metformin. Metformin also significantly (p<0.05) inhibited L-arginine-induced MPO, lactate dehydrogenase (LDH), and the inflammatory biomarker tumor necrosis factor alpha (TNF-α). Whereas, metformin significantly (p<0.05) increased IL-10 levels that were inhibited by pancreatitis induction. We further demonstrated a significant (p<0.001) correlation between the scoring of the degree of pancreatic lobules damage tissue damage and the blood levels of TNF-α, IL-10, LDH, and MPO. Thus, metformin effectively protects against L-arginine-induced acute pancreatitis, which is associated with the inhibition of MPO and augmentation of IL-10.
author	Al-Hashem,Fahaid
author_facet	Al-Hashem,Fahaid
author_sort	Al-Hashem,Fahaid
title	Suppression of L-Arginine-Induced Acute Necrotizing Pancreatitis in Rats by Metformin Associated with the Inhibition of Myeloperoxidase and Activation of Interleukin-10
title_short	Suppression of L-Arginine-Induced Acute Necrotizing Pancreatitis in Rats by Metformin Associated with the Inhibition of Myeloperoxidase and Activation of Interleukin-10
title_full	Suppression of L-Arginine-Induced Acute Necrotizing Pancreatitis in Rats by Metformin Associated with the Inhibition of Myeloperoxidase and Activation of Interleukin-10
title_fullStr	Suppression of L-Arginine-Induced Acute Necrotizing Pancreatitis in Rats by Metformin Associated with the Inhibition of Myeloperoxidase and Activation of Interleukin-10
title_full_unstemmed	Suppression of L-Arginine-Induced Acute Necrotizing Pancreatitis in Rats by Metformin Associated with the Inhibition of Myeloperoxidase and Activation of Interleukin-10
title_sort	suppression of l-arginine-induced acute necrotizing pancreatitis in rats by metformin associated with the inhibition of myeloperoxidase and activation of interleukin-10
publisher	Sociedad Chilena de Anatomía
publishDate	2021
url	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0717-95022021000100102
work_keys_str_mv	AT alhashemfahaid suppressionoflarginineinducedacutenecrotizingpancreatitisinratsbymetforminassociatedwiththeinhibitionofmyeloperoxidaseandactivationofinterleukin10
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Suppression of L-Arginine-Induced Acute Necrotizing Pancreatitis in Rats by Metformin Associated with the Inhibition of Myeloperoxidase and Activation of Interleukin-10

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