Oxidative stress in distant organs and the effects of allopurinol during experimental acute pancreatitis

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Abstract

Background. The present study was aimed at an assessment of the role of oxygen-derived free radicals in the development of local and systemic manifestations of L-arginine (Arg)-induced acute pancreatitis and at an evaluation of the protective effect of the xanthine oxidase inhibitor allopurinol. Methods. Acute pancreatitis was induced in male Wistar rats by injecting 2 x 250 mg/100 g body weight of Arg intraperitoneally at an interval of 1 h, as a 20% solution in 0.15 M NaCl. Control rats received the same quantity of glycine. In a third group, 200 mg/kg of allopurinol was administered subcutaneously 30 min before the first Arg injection. Rats were killed at 6, 12, 24, or 48 h following Arg administration. Acute pancreatitis was confirmed by a serum amylase level elevation and typical inflammatory features were observed microscopically. Tissue concentrations of malonyl dialdehyde (MDA), superoxide dismutase (Mn- and Cu,Zn-SOD), glutathione peroxidase (GPx), and catalase were measured in the pancreas, liver, and kidney. Results. The tissue concentration of MDA was significantly elevated in each organ. The activities of Mn-SOD, Cu,Zn-SOD, GPx, and catalase were quickly depleted in the pancreas and kidney, whereas only the Mn-SOD and GPx activities were reduced in the liver after the onset of pancreatitis. Histologic examination revealed acinar cell necrosis in the pancreas, but only mild alterations in the liver and kidney. Allopurinol pretreatment prevented the generation of reactive oxygen metabolites in the pancreas and reduced their formation in the kidney. Conclusion. Oxygen-derived free radicals are generated in the pancreas, liver, and kidney at an early stage of Arg-induced acute pancreatitis. The liver and the kidney, but not the pancreas, are able to defend against oxidative stress. The prophylactic application of allopurinol significantly restrains the generation of free radicals in pancreas and kidney.

Original languageEnglish
Pages (from-to)209-216
Number of pages8
JournalInternational Journal of Pancreatology
Volume27
Issue number3
Publication statusPublished - 2000

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Allopurinol
Pancreatitis
Pancreas
Oxidative Stress
Kidney
Arginine
Glutathione Peroxidase
Liver
Superoxide Dismutase
Free Radicals
manganese peroxidase
Oxygen
Catalase
Xanthine Oxidase
Acinar Cells
Amylases
Glycine
Wistar Rats
Necrosis
Body Weight

Keywords

  • Acute pancreatitis
  • Allopurinol
  • Kidney
  • L-arginine
  • Liver
  • Oxygen-derived free radicals
  • Scavengers

ASJC Scopus subject areas

  • Gastroenterology
  • Endocrinology
  • Oncology

Cite this

@article{ddad78cfb2f84e0da25e39fd00551523,
title = "Oxidative stress in distant organs and the effects of allopurinol during experimental acute pancreatitis",
abstract = "Background. The present study was aimed at an assessment of the role of oxygen-derived free radicals in the development of local and systemic manifestations of L-arginine (Arg)-induced acute pancreatitis and at an evaluation of the protective effect of the xanthine oxidase inhibitor allopurinol. Methods. Acute pancreatitis was induced in male Wistar rats by injecting 2 x 250 mg/100 g body weight of Arg intraperitoneally at an interval of 1 h, as a 20{\%} solution in 0.15 M NaCl. Control rats received the same quantity of glycine. In a third group, 200 mg/kg of allopurinol was administered subcutaneously 30 min before the first Arg injection. Rats were killed at 6, 12, 24, or 48 h following Arg administration. Acute pancreatitis was confirmed by a serum amylase level elevation and typical inflammatory features were observed microscopically. Tissue concentrations of malonyl dialdehyde (MDA), superoxide dismutase (Mn- and Cu,Zn-SOD), glutathione peroxidase (GPx), and catalase were measured in the pancreas, liver, and kidney. Results. The tissue concentration of MDA was significantly elevated in each organ. The activities of Mn-SOD, Cu,Zn-SOD, GPx, and catalase were quickly depleted in the pancreas and kidney, whereas only the Mn-SOD and GPx activities were reduced in the liver after the onset of pancreatitis. Histologic examination revealed acinar cell necrosis in the pancreas, but only mild alterations in the liver and kidney. Allopurinol pretreatment prevented the generation of reactive oxygen metabolites in the pancreas and reduced their formation in the kidney. Conclusion. Oxygen-derived free radicals are generated in the pancreas, liver, and kidney at an early stage of Arg-induced acute pancreatitis. The liver and the kidney, but not the pancreas, are able to defend against oxidative stress. The prophylactic application of allopurinol significantly restrains the generation of free radicals in pancreas and kidney.",
keywords = "Acute pancreatitis, Allopurinol, Kidney, L-arginine, Liver, Oxygen-derived free radicals, Scavengers",
author = "L. Czak{\'o} and T. Tak{\'a}cs and I. Varga and L. Tiszlavicz and Hai, {D. Q.} and P. Hegyi and B. Matkovics and J. Lonovics",
year = "2000",
language = "English",
volume = "27",
pages = "209--216",
journal = "Journal of Gastrointestinal Cancer",
issn = "1941-6628",
publisher = "Humana Press",
number = "3",

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TY - JOUR

T1 - Oxidative stress in distant organs and the effects of allopurinol during experimental acute pancreatitis

AU - Czakó, L.

AU - Takács, T.

AU - Varga, I.

AU - Tiszlavicz, L.

AU - Hai, D. Q.

AU - Hegyi, P.

AU - Matkovics, B.

AU - Lonovics, J.

PY - 2000

Y1 - 2000

N2 - Background. The present study was aimed at an assessment of the role of oxygen-derived free radicals in the development of local and systemic manifestations of L-arginine (Arg)-induced acute pancreatitis and at an evaluation of the protective effect of the xanthine oxidase inhibitor allopurinol. Methods. Acute pancreatitis was induced in male Wistar rats by injecting 2 x 250 mg/100 g body weight of Arg intraperitoneally at an interval of 1 h, as a 20% solution in 0.15 M NaCl. Control rats received the same quantity of glycine. In a third group, 200 mg/kg of allopurinol was administered subcutaneously 30 min before the first Arg injection. Rats were killed at 6, 12, 24, or 48 h following Arg administration. Acute pancreatitis was confirmed by a serum amylase level elevation and typical inflammatory features were observed microscopically. Tissue concentrations of malonyl dialdehyde (MDA), superoxide dismutase (Mn- and Cu,Zn-SOD), glutathione peroxidase (GPx), and catalase were measured in the pancreas, liver, and kidney. Results. The tissue concentration of MDA was significantly elevated in each organ. The activities of Mn-SOD, Cu,Zn-SOD, GPx, and catalase were quickly depleted in the pancreas and kidney, whereas only the Mn-SOD and GPx activities were reduced in the liver after the onset of pancreatitis. Histologic examination revealed acinar cell necrosis in the pancreas, but only mild alterations in the liver and kidney. Allopurinol pretreatment prevented the generation of reactive oxygen metabolites in the pancreas and reduced their formation in the kidney. Conclusion. Oxygen-derived free radicals are generated in the pancreas, liver, and kidney at an early stage of Arg-induced acute pancreatitis. The liver and the kidney, but not the pancreas, are able to defend against oxidative stress. The prophylactic application of allopurinol significantly restrains the generation of free radicals in pancreas and kidney.

AB - Background. The present study was aimed at an assessment of the role of oxygen-derived free radicals in the development of local and systemic manifestations of L-arginine (Arg)-induced acute pancreatitis and at an evaluation of the protective effect of the xanthine oxidase inhibitor allopurinol. Methods. Acute pancreatitis was induced in male Wistar rats by injecting 2 x 250 mg/100 g body weight of Arg intraperitoneally at an interval of 1 h, as a 20% solution in 0.15 M NaCl. Control rats received the same quantity of glycine. In a third group, 200 mg/kg of allopurinol was administered subcutaneously 30 min before the first Arg injection. Rats were killed at 6, 12, 24, or 48 h following Arg administration. Acute pancreatitis was confirmed by a serum amylase level elevation and typical inflammatory features were observed microscopically. Tissue concentrations of malonyl dialdehyde (MDA), superoxide dismutase (Mn- and Cu,Zn-SOD), glutathione peroxidase (GPx), and catalase were measured in the pancreas, liver, and kidney. Results. The tissue concentration of MDA was significantly elevated in each organ. The activities of Mn-SOD, Cu,Zn-SOD, GPx, and catalase were quickly depleted in the pancreas and kidney, whereas only the Mn-SOD and GPx activities were reduced in the liver after the onset of pancreatitis. Histologic examination revealed acinar cell necrosis in the pancreas, but only mild alterations in the liver and kidney. Allopurinol pretreatment prevented the generation of reactive oxygen metabolites in the pancreas and reduced their formation in the kidney. Conclusion. Oxygen-derived free radicals are generated in the pancreas, liver, and kidney at an early stage of Arg-induced acute pancreatitis. The liver and the kidney, but not the pancreas, are able to defend against oxidative stress. The prophylactic application of allopurinol significantly restrains the generation of free radicals in pancreas and kidney.

KW - Acute pancreatitis

KW - Allopurinol

KW - Kidney

KW - L-arginine

KW - Liver

KW - Oxygen-derived free radicals

KW - Scavengers

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