Nontoxic heat shock protein coinducer BRX-220 protects against acute pancreatitis in rats

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Background: Nontoxic heat shock protein (HSP) inducer compounds open up promising therapeutic possibilities by activating one of the natural and highly conserved defense mechanisms of the organism. Aims: In the present experiments, we examined the effects of a HSP coinducer drug-candidate, BRX-220, on the cholecystokinin-octapeptide (CCK)-induced acute pancreatitis in rats. Methods: Male Wistar rats weighing 240 to 270 g were divided into two groups. In group B, 20 mg/kg BRX-220 was administered orally, followed by 75 μg/kg CCK subcutaneously three times, after 1, 3, and 5 h. This whole procedure was repeated for 5 d. The aminals in group ∅B received physiological saline orally instead of BRX-220, but otherwise the protocol was the same as in group B. The rats were exsanguinated through the abdominal aorta 12 h after the last administration of CCK. We determined the serum amylase activity, the plasma trypsinogen activation peptide concentration, the pancreatic weight/body weight ratio, the DNA and total protein contents of the pancreas, the levels of pancreatic HSP60 and HSP72, the activities of pancreatic amylase, lipase, trypsinogen, and free radical scavenger enzymes (superoxide dismutase, catalase, and glutathione peroxidase), the degree of lipid peroxidation, protein oxidation, and the reduced glutathione level. Histopathological investigation of the pancreas was also performed in all cases. Results: Repeated CCK treatment resulted in the typical laboratory and morphological changes of experimentally induced pancreatitis. The pancreatic levels of HSP60 and HSP72 were significantly increased in the animals treated with BRX-220. In group B, the pancreatic total protein content and the amylase and trypsinogen activities were significantly higher vs. group ∅B. The plasma trypsinogen activation peptide concentration, and the pancreatic lipid peroxidation, protein oxidation, and the activity of Cu/Zn-superoxide dismutase were significantly decreased in group B vs. group ∅B, whereas the glutathione peroxidase activity was increased. The morphological damage in group B was significantly lower than that in group ∅B. Conclusion: The HSP coinducer BRX-220, administered for 5 d, has a protective effect against CCK-induced acute pancreatitis.

Original languageEnglish
Pages (from-to)1283-1292
Number of pages10
JournalFree Radical Biology and Medicine
Volume32
Issue number12
DOIs
Publication statusPublished - Jun 15 2002

Fingerprint

Sincalide
Heat-Shock Proteins
Pancreatitis
Rats
trypsinogen activation peptide
Amylases
Trypsinogen
Glutathione Peroxidase
Lipid Peroxidation
Pancreas
Proteins
Lipids
Plasmas
Oxidation
Free Radical Scavengers
Abdominal Aorta
Weighing
Lipase
Catalase
Superoxide Dismutase

Keywords

  • BRX-220
  • Cholecystokinin-octapeptide
  • Coinducer
  • Free radicals
  • Heat shock protein
  • Pancreatitis

ASJC Scopus subject areas

  • Medicine(all)
  • Toxicology
  • Clinical Biochemistry

Cite this

@article{edf4392a4e044bbfb08623430989cc68,
title = "Nontoxic heat shock protein coinducer BRX-220 protects against acute pancreatitis in rats",
abstract = "Background: Nontoxic heat shock protein (HSP) inducer compounds open up promising therapeutic possibilities by activating one of the natural and highly conserved defense mechanisms of the organism. Aims: In the present experiments, we examined the effects of a HSP coinducer drug-candidate, BRX-220, on the cholecystokinin-octapeptide (CCK)-induced acute pancreatitis in rats. Methods: Male Wistar rats weighing 240 to 270 g were divided into two groups. In group B, 20 mg/kg BRX-220 was administered orally, followed by 75 μg/kg CCK subcutaneously three times, after 1, 3, and 5 h. This whole procedure was repeated for 5 d. The aminals in group ∅B received physiological saline orally instead of BRX-220, but otherwise the protocol was the same as in group B. The rats were exsanguinated through the abdominal aorta 12 h after the last administration of CCK. We determined the serum amylase activity, the plasma trypsinogen activation peptide concentration, the pancreatic weight/body weight ratio, the DNA and total protein contents of the pancreas, the levels of pancreatic HSP60 and HSP72, the activities of pancreatic amylase, lipase, trypsinogen, and free radical scavenger enzymes (superoxide dismutase, catalase, and glutathione peroxidase), the degree of lipid peroxidation, protein oxidation, and the reduced glutathione level. Histopathological investigation of the pancreas was also performed in all cases. Results: Repeated CCK treatment resulted in the typical laboratory and morphological changes of experimentally induced pancreatitis. The pancreatic levels of HSP60 and HSP72 were significantly increased in the animals treated with BRX-220. In group B, the pancreatic total protein content and the amylase and trypsinogen activities were significantly higher vs. group ∅B. The plasma trypsinogen activation peptide concentration, and the pancreatic lipid peroxidation, protein oxidation, and the activity of Cu/Zn-superoxide dismutase were significantly decreased in group B vs. group ∅B, whereas the glutathione peroxidase activity was increased. The morphological damage in group B was significantly lower than that in group ∅B. Conclusion: The HSP coinducer BRX-220, administered for 5 d, has a protective effect against CCK-induced acute pancreatitis.",
keywords = "BRX-220, Cholecystokinin-octapeptide, Coinducer, Free radicals, Heat shock protein, Pancreatitis",
author = "Z. Rakonczay and B. Iv{\'a}nyi and I. Varga and I. Boros and Andrea Jedn{\'a}kovits and I. N{\'e}meth and J. Lonovics and T. Tak{\'a}cs",
year = "2002",
month = "6",
day = "15",
doi = "10.1016/S0891-5849(02)00833-X",
language = "English",
volume = "32",
pages = "1283--1292",
journal = "Free Radical Biology and Medicine",
issn = "0891-5849",
publisher = "Elsevier Inc.",
number = "12",

}

TY - JOUR

T1 - Nontoxic heat shock protein coinducer BRX-220 protects against acute pancreatitis in rats

AU - Rakonczay, Z.

AU - Iványi, B.

AU - Varga, I.

AU - Boros, I.

AU - Jednákovits, Andrea

AU - Németh, I.

AU - Lonovics, J.

AU - Takács, T.

PY - 2002/6/15

Y1 - 2002/6/15

N2 - Background: Nontoxic heat shock protein (HSP) inducer compounds open up promising therapeutic possibilities by activating one of the natural and highly conserved defense mechanisms of the organism. Aims: In the present experiments, we examined the effects of a HSP coinducer drug-candidate, BRX-220, on the cholecystokinin-octapeptide (CCK)-induced acute pancreatitis in rats. Methods: Male Wistar rats weighing 240 to 270 g were divided into two groups. In group B, 20 mg/kg BRX-220 was administered orally, followed by 75 μg/kg CCK subcutaneously three times, after 1, 3, and 5 h. This whole procedure was repeated for 5 d. The aminals in group ∅B received physiological saline orally instead of BRX-220, but otherwise the protocol was the same as in group B. The rats were exsanguinated through the abdominal aorta 12 h after the last administration of CCK. We determined the serum amylase activity, the plasma trypsinogen activation peptide concentration, the pancreatic weight/body weight ratio, the DNA and total protein contents of the pancreas, the levels of pancreatic HSP60 and HSP72, the activities of pancreatic amylase, lipase, trypsinogen, and free radical scavenger enzymes (superoxide dismutase, catalase, and glutathione peroxidase), the degree of lipid peroxidation, protein oxidation, and the reduced glutathione level. Histopathological investigation of the pancreas was also performed in all cases. Results: Repeated CCK treatment resulted in the typical laboratory and morphological changes of experimentally induced pancreatitis. The pancreatic levels of HSP60 and HSP72 were significantly increased in the animals treated with BRX-220. In group B, the pancreatic total protein content and the amylase and trypsinogen activities were significantly higher vs. group ∅B. The plasma trypsinogen activation peptide concentration, and the pancreatic lipid peroxidation, protein oxidation, and the activity of Cu/Zn-superoxide dismutase were significantly decreased in group B vs. group ∅B, whereas the glutathione peroxidase activity was increased. The morphological damage in group B was significantly lower than that in group ∅B. Conclusion: The HSP coinducer BRX-220, administered for 5 d, has a protective effect against CCK-induced acute pancreatitis.

AB - Background: Nontoxic heat shock protein (HSP) inducer compounds open up promising therapeutic possibilities by activating one of the natural and highly conserved defense mechanisms of the organism. Aims: In the present experiments, we examined the effects of a HSP coinducer drug-candidate, BRX-220, on the cholecystokinin-octapeptide (CCK)-induced acute pancreatitis in rats. Methods: Male Wistar rats weighing 240 to 270 g were divided into two groups. In group B, 20 mg/kg BRX-220 was administered orally, followed by 75 μg/kg CCK subcutaneously three times, after 1, 3, and 5 h. This whole procedure was repeated for 5 d. The aminals in group ∅B received physiological saline orally instead of BRX-220, but otherwise the protocol was the same as in group B. The rats were exsanguinated through the abdominal aorta 12 h after the last administration of CCK. We determined the serum amylase activity, the plasma trypsinogen activation peptide concentration, the pancreatic weight/body weight ratio, the DNA and total protein contents of the pancreas, the levels of pancreatic HSP60 and HSP72, the activities of pancreatic amylase, lipase, trypsinogen, and free radical scavenger enzymes (superoxide dismutase, catalase, and glutathione peroxidase), the degree of lipid peroxidation, protein oxidation, and the reduced glutathione level. Histopathological investigation of the pancreas was also performed in all cases. Results: Repeated CCK treatment resulted in the typical laboratory and morphological changes of experimentally induced pancreatitis. The pancreatic levels of HSP60 and HSP72 were significantly increased in the animals treated with BRX-220. In group B, the pancreatic total protein content and the amylase and trypsinogen activities were significantly higher vs. group ∅B. The plasma trypsinogen activation peptide concentration, and the pancreatic lipid peroxidation, protein oxidation, and the activity of Cu/Zn-superoxide dismutase were significantly decreased in group B vs. group ∅B, whereas the glutathione peroxidase activity was increased. The morphological damage in group B was significantly lower than that in group ∅B. Conclusion: The HSP coinducer BRX-220, administered for 5 d, has a protective effect against CCK-induced acute pancreatitis.

KW - BRX-220

KW - Cholecystokinin-octapeptide

KW - Coinducer

KW - Free radicals

KW - Heat shock protein

KW - Pancreatitis

UR - http://www.scopus.com/inward/record.url?scp=0037096195&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037096195&partnerID=8YFLogxK

U2 - 10.1016/S0891-5849(02)00833-X

DO - 10.1016/S0891-5849(02)00833-X

M3 - Article

C2 - 12057766

AN - SCOPUS:0037096195

VL - 32

SP - 1283

EP - 1292

JO - Free Radical Biology and Medicine

JF - Free Radical Biology and Medicine

SN - 0891-5849

IS - 12

ER -