Skip to main content
SpringerLink
Log in

Involvement of Oxygen-Derived Free Radicals in L-Arginine-Induced Acute Pancreatitis

  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

This study was aimed at an assessment of the role of oxygen-derived free radicals in the pathogenesis of L-arginine (Arg)-induced acute pancreatitis in rat, by measuring the levels of malonyl dialdehyde (MDA), glutathione peroxidase (GPx), catalase, and superoxide dismutase (Mn- and Cu,Zn-SOD) in the pancreatic tissue, and evaluating the protective effect of the xanthine oxidase inhibitor allopurinol. Acute pancreatitis was induced in male Wistar rats by injecting 2 × 250 mg/100 g body weight of Arg intraperitoneally in a 1-hr interval, as a 20% solution in 0.15 M NaCl. Control rats received the same quantity of glycine. Allopurinol, 100 or 200 mg/kg, was administered subcutaneously 30 min before the first Arg injection. Rats were killed at 6, 12, 24, and 48 hr following Arg administration, and acute pancreatitis was confirmed by a serum amylase level elevation and typical inflammatory features observed microscopically. The serum level of amylase reached the peak level at 24 hr after the Arg injection (30,800 ± 3813 vs 6382 ± 184 units/liter in the control) and normalized at 48 hr. The tissue concentration of MDA was significantly elevated at 24 hr and reached the peak value at 48 hr (5.00 ± 1.75 vs 0.28 ± 0.05 nM/mg protein in the control). The catalase and Mn-SOD activities were significantly decreased throughout the study, while the GPx activity was significantly reduced at 6 and 12 hr, and the Cu,Zn-SOD activity was significantly lower at 12 hr after the Arg injection as compared with the controls. Allopurinol treatment markedly reduced the serum amylase elevation (12.631 ± 2.257 units/liter at 24 hr) and prevented the increase in tissue MDA concentration (0.55 ± 0.09 nM/mg protein at 48 hr). Both doses of allopurinol significantly ameliorated the pancreatic edema, necrosis, and inflammation at 48 hr after Arg administration. Oxygen-derived free radicals are generated at an early stage of Arg-induced acute pancreatitis. Prophylactic allopurinol treatment prevents the generation of reactive oxygen metabolites, reduces the serum amylase concentration, and exerts a beneficial effect on the development of histopathological changes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. Goldberg RC, Chaikoff IL: Selective pancre atic acinar destruction by d-ethionine. Arch Pathol 52:230 - 238, 1951

    Google Scholar 

  2. Kaufman N, Klavins JV, Kinney TD: Pancre atic damage induced by exce ss methionine. Arch Pathol 70:331- 337, 1960

    Google Scholar 

  3. Nakano S, Watanabe N, Kihara Y, Ogami Y, Otsuki M: New model of acute pancre atitis induced by exce ssive doses of lysine in rats. Int J Pancre tol 12:83, 1992

    Google Scholar 

  4. Mizunuma T, Kawamura S, Kishino Y: Effects of injecting excess arginine on rat pancre as. J Nutr 114:467- 471, 1984

    Google Scholar 

  5. Tani S, Itoh H, Koide M, Okabayashi Y, Nakamura T, Fujii M, Fujisawa T, Koide M, Otsuki M: New mode l of acute necrotizing pancre atitis induced by exce ssive does of arginine in rats. Dig Dis Sci 35:367- 374, 1990

    Google Scholar 

  6. Delaney CP, McGee ney KF, Dervan P, Fitzpatrick JM: Pancre atic atrophy: A new model using serial intra-peritoneal injections of L-arginine. Scand J Gastroenterol 28:1086 - 1090, 1993

    Google Scholar 

  7. Sanfey H, Bulkley GB, Came ron JL: The pathogenesis of acute pancre atitis: The source and role of oxyge n-derived free radicals in three different expe rimental models. Ann Surg 201:633- 639, 1985

    Google Scholar 

  8. Schoenberg MH, Büchler M, Be ge r HG: Oxygen radicals in e xpe rime ntal acute panc re ati tis. He pato-Gastroe nte rol 41:313- 319, 1994

    Google Scholar 

  9. Wisner JR, Renner IG: Allopurinol attenuates cae rulein induced acute pancreatitis in the rat. Gut 29:926 - 929, 1988

    Google Scholar 

  10. Sweiry JH, Mann GE: Role of oxidative stress in the pathogenesis of acute pancre atitis. Scand J Gastroente rol 31( suppl 219): 10 - 15, 1996

    Google Scholar 

  11. Fridovich I: The biology of oxygen radicals. Science 201:875- 880, 1978

    Google Scholar 

  12. Sies H: Oxidative stress: From basic research to clinical application. Am J Med 91(suppl 3C): 31- 38, 1991

    Google Scholar 

  13. Parks DA, Granger DN: Xanthine oxidase: Biochemistry, distribution and physiology. Acta Physiol Scand 126( suppl 548): 87- 99, 1986

    Google Scholar 

  14. Takács T, Czakó L, Jármay K, Farkas G Jr, Mándi Y, Lonovics J: Cytokine level changes in L-arginine-induced acute pancre atitis in rat. Acta Physiol Hung 84:147- 156, 1996

    Google Scholar 

  15. Ceska M, Birath K, Brown B: A new and rapid me thod for the clinical determination of amylase activities in human serum and urine. Clin Chem Acta 26:437- 444, 1969

    Google Scholar 

  16. Placer ZA, Cushman L, Johnson BC: Estimation of product of lipid peroxidation (malonyl dialdehydes) in biochemical systems. Anal Biochem 16:359 - 364, 1966

    Google Scholar 

  17. Misra HP, Fridovich I: The role of superoxide anion in autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem 247:3170 - 3175, 1972

    Google Scholar 

  18. Beauchamp C, Fridovich I: Superoxide dismutase: Improved assay and an assay applicable to acrylamide ge ls. Anal Biochem 44:276 - 287, 1971

    Google Scholar 

  19. Beers RF Jr, Sizer IW: Spectrophotometric me thod for measuring the breakdown of hydrogen peroxide by catalase. J Biol Chem 195:133- 140, 1951

    Google Scholar 

  20. Sedlak J, Lindsay RH: Estimation of total, protein-bound, and nonprotein sulfhydryls groups in tissue with Ellman's reagent. Anal Biochem 25:192- 205, 1968

    Google Scholar 

  21. Chiu DT, Stults FH, Tappe l AL: Purification and properties of rat lung soluble glutathione peroxidase. Biochim Biophys Acta 445:558 - 566, 1976

    Google Scholar 

  22. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ: Protein me asurements with the Folin phenol reage nt. J Biol Chem 193:265- 275, 1951

    Google Scholar 

  23. Takeda Y, Tominaga T, Tei N, Kitamura M, Taga T, Murase J, Taguchi T, Miwatani T: Inhibitory effect of L-arginine on growth of rat mammary tumors induced by 7,12-dime thylbenz(α)anthrace ne. Cancer Res 35:2390 - 2393, 1975

    Google Scholar 

  24. Nakaki T, Hishikiwa K, Suzuki H, Saruta T, Kato R: L-Arginine-induced hypotension. Lancet 336:1016, 1992

    Google Scholar 

  25. Sakuma I, Sruehr D, Gross SS, Nathan C, Levi R: Identification of arginine as a precursor of endothelium-derived re laxing factor. Proc Natl Acad Sci USA 85:8664 - 8667, 1988

    Google Scholar 

  26. Varga IS, Matkovics B, Czakó L, Hai DQ, Kotormán M, Takács T, Sasvári M: Oxidative stress changes in L-arginineinduced pancre atitis in rats. Pancre as 14:355- 359, 1997

    Google Scholar 

  27. Kle in AS, Joh JW, Rangan U, Wang D, Bulkley GB: Allopurinol: Discrimination of antioxidant from enzyme inhibitory activities. Fre e Radic Biol Med 21:713- 717, 1996

    Google Scholar 

  28. Lankisch PG, Pohl U, Otto J, Wereszczyns ka-Siemiatkowska U, Gröne HJ: Xanthine oxidase inhibitor in acute experimental pancre atitis in rats and mice. Pancreas 4:436 - 440, 1989

    Google Scholar 

  29. Niede rau C, Niederau M, Borchard F, Ude K, Luthen R, Strohmeyer G, Ferrell LD, Grendell JH: Effects of antioxidants and free radical scave nge rs in three different models of acute pancre atitis. Pancre as 7:486 - 496, 1992

    Google Scholar 

  30. Braganza JM: Experimental acute pancre atitis. Curr Opin Gastroenterol 6:763- 768, 1990

    Google Scholar 

Download references

Authors
  1. Laszlo Czako
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tamas Takacs
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ilona Sz. Varga
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Laszlo Tiszlavicz
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Do Quy Hai
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Peter Hegyi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Bela Matkovics
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Janos Lonovics
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Czako, L., Takacs, T., Varga, I.S. et al. Involvement of Oxygen-Derived Free Radicals in L-Arginine-Induced Acute Pancreatitis. Dig Dis Sci 43, 1770–1777 (1998). https://doi.org/10.1023/A:1018839821176

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1018839821176

Search

Navigation