Free radical generation coupled with arachidonate lipoxygenase reaction relates to reoxygenation induced myocardial cell injury - PubMed (original) (raw)

. 1993 Jun;27(6):1056-60.

doi: 10.1093/cvr/27.6.1056.

Affiliations

• PMID: 8221764
• DOI: 10.1093/cvr/27.6.1056

Free radical generation coupled with arachidonate lipoxygenase reaction relates to reoxygenation induced myocardial cell injury

T Kuzuya et al. Cardiovasc Res. 1993 Jun.

Abstract

Objective: The role of arachidonate lipoxygenase activity in reoxygenation induced cell injury in adult canine cardiac myocytes was investigated.

Methods: The production of hydroxyeicosatetraenoic acids (HETEs), which are lipoxygenase metabolites, was measured with high pressure liquid chromatography in canine cardiac myocytes cultured under hypoxic conditions and then reoxygenated. Free radical generation was evaluated by electron paramagnetic resonance spectroscopy with a spin trapper, 5,5-dimethyl-1-pyrroline N-oxide (DMPO) and luminol enhanced chemiluminescence emission. Cell injury was estimated in terms of morphological changes and release of intracellular enzymes. Morphological damage to myocytes was quantified in terms of the percentage of hypercontracted "round" cells. The effects of nordihydroguaiaretic acid, AA-861, mepacrine, indomethacin, aspirin, alpha tocopherol, and 2-0-octadecylascorbic acid (CV-3611) on lipoxygenase metabolism, free radical generation and cell injury were also assessed.

Results: Cardiac myocytes produced 5-HETE and 12-HETE at less than 0.1 ng.mg-1 protein under normoxic conditions. Production of HETE was greatly increased at five hours of reoxygenation after 45 minutes of hypoxia [5-HETE = 12.0(SEM 0.5), 12-HETE = 23.6(1.1) ng.mg-1 protein]. Both DMPO-OH adduct generation and chemiluminescence emission were considerably increased after one to three hours of reoxygenation, although they increased only slightly after 45 minutes of hypoxia. After five hours of reoxygenation, long rod cells gradually became deformed; 92.0% of the cells were converted to hypercontracted "round" cells. Cell injury and HETE production were significantly suppressed by nordihydroguaiaretic acid (10 microM), AA-861 (2 microM), and mepacrine (10 microM). Indomethacin (10 microM) and aspirin (50 microM) enhanced cell injury and HETE production. alpha Tocopherol and CV-3611 greatly suppressed cell injury and free radical generation, but not HETE production.

Conclusion: The arachidonate lipoxygenase metabolic pathway may have an important role in reoxygenation induced myocardial cell injury in adult cardiac myocytes, possibly because of the generation of free radicals.

PubMed Disclaimer

Similar articles

• Generation of free radicals in Langendorff and working hearts during normoxia, hypoxia, and reoxygenation.
  Damerau W, Ibel J, Thürich T, Assadnazari H, Zimmer G. Damerau W, et al. Basic Res Cardiol. 1993 Mar-Apr;88(2):141-9. doi: 10.1007/BF00798262. Basic Res Cardiol. 1993. PMID: 8389121
• Oxygen radical generation and enzymatic properties of mitochondria in hypoxia/reoxygenation.
  Zwicker K, Dikalov S, Matuschka S, Mainka L, Hofmann M, Khramtsov V, Zimmer G. Zwicker K, et al. Arzneimittelforschung. 1998 Jun;48(6):629-36. Arzneimittelforschung. 1998. PMID: 9689418
• Molecular oxygen: friend and foe. The role of the oxygen free radical system in the calcium paradox, the oxygen paradox and ischemia/reperfusion injury.
  Hess ML, Manson NH. Hess ML, et al. J Mol Cell Cardiol. 1984 Nov;16(11):969-85. doi: 10.1016/s0022-2828(84)80011-5. J Mol Cell Cardiol. 1984. PMID: 6394765 Review.
• Roles of hydroxyeicosatetraenoic acids in diabetes (HETEs and diabetes).
  Dong L, Wang H, Chen K, Li Y. Dong L, et al. Biomed Pharmacother. 2022 Dec;156:113981. doi: 10.1016/j.biopha.2022.113981. Epub 2022 Nov 8. Biomed Pharmacother. 2022. PMID: 36411651 Review.

Cited by

• 12(S)-hydroperoxyeicosatetraenoic acid (12-HETE) increases mitochondrial nitric oxide by increasing intramitochondrial calcium.
  Nazarewicz RR, Zenebe WJ, Parihar A, Parihar MS, Vaccaro M, Rink C, Sen CK, Ghafourifar P. Nazarewicz RR, et al. Arch Biochem Biophys. 2007 Dec 1;468(1):114-20. doi: 10.1016/j.abb.2007.09.018. Epub 2007 Sep 29. Arch Biochem Biophys. 2007. PMID: 17963719 Free PMC article.
• Eicosanoid signalling pathways in the heart.
  Jenkins CM, Cedars A, Gross RW. Jenkins CM, et al. Cardiovasc Res. 2009 May 1;82(2):240-9. doi: 10.1093/cvr/cvn346. Epub 2008 Dec 14. Cardiovasc Res. 2009. PMID: 19074824 Free PMC article. Review.
• Eicosanoids participate in the regulation of cardiac glucose transport by contribution to a rearrangement of actin cytoskeletal elements.
  Dransfeld O, Rakatzi I, Sasson S, Gruzman A, Schmitt M, Häussinger D, Eckel J. Dransfeld O, et al. Biochem J. 2001 Oct 1;359(Pt 1):47-54. doi: 10.1042/0264-6021:3590047. Biochem J. 2001. PMID: 11563968 Free PMC article.
• Cyclooxygenase-mediated generation of free radicals during hypoxia in the cerebral cortex of newborn piglets.
  Torres L, Anderson C, Marro P, Mishra OP, Delivoria-Papadopoulos M. Torres L, et al. Neurochem Res. 2004 Oct;29(10):1825-30. doi: 10.1023/b:nere.0000042208.20730.23. Neurochem Res. 2004. PMID: 15532537
• Reactive oxygen intermediates increase vascular endothelial growth factor expression in vitro and in vivo.
  Kuroki M, Voest EE, Amano S, Beerepoot LV, Takashima S, Tolentino M, Kim RY, Rohan RM, Colby KA, Yeo KT, Adamis AP. Kuroki M, et al. J Clin Invest. 1996 Oct 1;98(7):1667-75. doi: 10.1172/JCI118962. J Clin Invest. 1996. PMID: 8833917 Free PMC article.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Silverchair Information Systems