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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2002; 48(3): 34-40


The influenceof exogenous leukotrienes and lipoxygenase inhibitors on apoptosis and necrosisin rat cultured hepatocytes.

G.N. Korniychuk N.V. Makogon I.N. Alexeyeva I.V. Lushnikova

    A.A. Bogomoletz Institute of Physiology


Abstract

Liver cell death by apoptosis and necrosis occurs upon the liver injury. Lipoxygenase pathway of arachidonic acid metabolism is known to regulate the viability and apoptosis in some cell types, but its role in hepatocyte cell death is not fully understood. We studied the influence of leukotrienes (LT) and lipoxygenase inhibitors on apoptosis and necrosis in rat hepatocyte primary culture by double staining with Hoechst 33342 and propidium iodide and electron microscopy. Treatment with general lipoxygenase inhibitor nordihydoguaiaretic acid and 5-lipoxygenase inhibitor сaffeic acid (2 . 10-5M) for 4 and 24 h indu- ced hepatocyte apoptosis. LTB4 and LTC4 (10-8M) decreased the number of living cells and increased the number of necrotic cells. LTs exerted the same necrotic effect on hepatocytes, treated with lipoxygenase inhi- bitors. It is important that LTs decreased apoptosis induced by inhibitors treatment. These data suggest that lipoxygenase pathway of arachidonic acid meta- bolism is important regulator of hepatocytes viability and apoptosis The increase of lipoxygenase product formation, in particular LTs, may diminish apoptosis and increase necrosis in hepatocytes upon the liver injury.

References

  1. Корнійчук Г.М., Макогон Н.В., Лушнікова І.В., Алексєєва І.М. Блокатори ліпоксигеназ індукують апоптоз гепатоцитів щурів в первинній культурі // Укр. біохім. журн. - 2002. - №1. - С.125-127.
  2. Матышевская О.П., Пастух В.Н., Солодушко В.А. Ингибирование липоксигеназной активности снижает индуцированную радиацией фрагментацию ДНК в лимфоцитах // Радиац. биология и радиоэкология - 1999. - 39, №2-3. -С.282-286.
  3. Feldmann G., Lamboley C., Moreau A. et al. Fasmediated apoptosis of hepatic cells //Biomed. Pharmacother. - 1998. - 2, N9. - P.378-385.
  4. Hayashi N., Mita E. Involvement of Fas systemmediated apoptosis in pathogenesis of viral hepatitis // J. Viral. Hepat. - 1999. - 6, N5. - P.357-365.
  5. Huwyler J., Gut J. Single-step organic extraction of leukotrienes and related compounds and their simultaneous analysis by high-performance liquid chromatography // Anal. Biochem. - 1990. - 1,N188(Pt2). - P.374-382.
  6. Kawada N., Mizoguchi Y., Sakagami Y. et al. Changes in leukotrienes and prostaglandins in the liver tissue of rats in experimental massive hepatic cell necrosis model // Prostagland. leukotr. EssentFatty Acids. - 1990. - 40, N2. - P.149-155.
  7. Keppler D. Leukotrienes: biosynthesis, transport,inactivation, and analysis // Rev. Physiol. Biochem. Pharmacol. – 1992. - 121.-P.1-31.
  8. Korystov Yu.N., Shaposhnikova V.V., Levitman M.Kh. et al. The effect of inhibitors of arachidonic acid metabolism on proliferation and death of tumor cells // FEBS Lett. - 1998. - 31, N2. -P.224-226.
  9. 9. Lemasters J.J. Necrapoptosis and the mitochondrial permeability transition: shared pathways to necrosis and apoptosis // Amer.J.Physiol. - 1999. -276. - P.G1-G6.
  10. 10. Makogon N.V., Korneitchuk A.N., Lushnikova I.V., Alexeyeva I.N. Effects of exogenous leukotrienes B4 and C4 on the viability of cultured rat hepatocytes // Acta Physiol. Pharmacol. Bulg. -2000. - N25. - P.87-91.
  11. Muhlenfeld K., Langner A. Biotransformation and toxicity of the lipoxygenase inhibitor 2-hydroxy5-methyllaurophenone oxime (FLM 5011) on Hep G2 cells // Arch. Pharm. (Weinheim). - 1998. -331, N7-8. - P.259-261.
  12. Myers CE., Ghosh J. Lipoxygenase inhibition in prostate cancer//Eur.Urol.-1999.- 35, N5-6.- P.395-398.
  13. Otomo Y., Kanda Y., Yoshino Y. et al. Production of leukotrienes in rat Kupffer cells and hepatocytes by various inducers // J. Jap. Surg.Soc. - 1993. -4, N3. - P.234-241.
  14. Tang D., Chen Y., Honn K. Arachidonate lipoxygenases as essential regulators of cell survival and apoptosis // Cell Biol. - 1996. - 93. - P. 5241-5246.
  15. Titos E., Claria J., Bataller R. et al. Hepatocyte-derived cysteinyl leukotrienes modulate vascular tone in experimental cirrhosis //Gastroenterology. - 2000. - 119, N3. -P.794-805.
  16. Wang J.H., Redmond H.P., Wu Q.D. et al. Nitric oxide mediates hepatocyte injury // Amer. J. Physiol. - 1998. -257, N5(Pt1). -G1117-1126.

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