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Planta Med 2000; 66(3): 199-205
DOI: 10.1055/s-2000-8566
Original Paper
Georg Thieme Verlag Stuttgart · New York

Effect of Sesquiterpene Lactones on Antioxidant Enzymes and Some Drug-Metabolizing Enzymes in Rat Liver and Kidney

Jadwiga Jodynis-Liebert1,*, Marek Murias1 , Elżbieta  Błoszyk2
  • 1 Department of Toxicology, Karol Marcinkowski University of Medical Sicences, Poznań, Poland
  • 2 Department of Medical Plants, Karol Marcinkowski University of Medical Sciences, Poznań, Poland
Further Information

Publication History

Publication Date:
31 December 2000 (online)

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Abstract

Previously we have reported that several sesquiterpene lactones isolated from Helenium aromaticum and Telekia speciosa showed pro-oxidative properties and caused glutathione level depletion in rat liver in vivo. In the present study we examined the in vivo effect of these lactones on antioxidant enzyme systems and some drug metabolizing enzymes in the liver and the kidney of rats. We found that the majority of the compounds increased the hepatic activity of glutathione peroxidase (GPx), glutathione reductase (GR), and catalase (CAT), but superoxide dismutase (SOD) activity was distinctly lowered by five lactones. A few of the compounds tested caused a decrease in the hepatic cytochrome P450 content and reduced the activity of NADPH-cytochrome P450 reductase, aminopyrine demethylase, aniline hydroxylase and glutathione-S-transferase. Results for the kidney showed fewer changes in activities of both classes of enzymes when compared to the liver. Not all lactones affected the enzymes under test, the most active were: linifolin, helenalin, mexicanin I and telekin. 6α-Hydroxy-2,3-dihydroaromaticin behaved differently towards monooxygenases since it induced the activity of aminopyrine demethylase and aniline hydroxylase.

Abbreviations

GPx:glutathione peroxidase CAT:catalase SOD:superoxide dismutase G6PD:glucose-6-phosphate dehydrogenase GST:glutathione-S-transferase GR:glutathione reductase CDNB:1-chloro-2,4-dinitrobenzene

Key words

Sesquiterpene lactones - Helenium aromaticum - Telekia speciosa - Compositae - antioxidant enzymes - cytochrome P450 monooxygenases

References

  • 1 Marles  R J,, Pazos-Sanou  L,, Compadre  C M,, Pezutto  J M,, Błoszyk  E,, Arnason  T.. Sesquiterpene lactones revisited. In: Arnason JT, Mata R, Romeo JT, editors Recent advances in phytochemistry, vol. 29. Phytochemistry of Medicinal Plants Plenum Press, New York and London; 1995; Chapter 13: 334-40
    Google Scholar
  • 2 Robles  M,, Aregullin  M,, West  J,, Rodriguez  E.. Recent Studies on the zoopharmacognosy, pharmacology and neurotoxicity of sesquiterpene lactones.  Planta Medica. 1995;;  61 199-203
    PubMedGoogle Scholar
  • 3 Hwang  D,, Fisher  N H,, Jang  B C,, Tak  H,, Kim  J K,, Lee  W.. Inhibition of the expression of inducible cyclooxygenase and proinflammatory cytokines by sesquiterpene lactones in macrophages correlates with the inhibition of MAP kinases.  Biochemical and Biopyhsical Research Communications. 1996;;  226 810-8
    PubMedGoogle Scholar
  • 4 Blanco  J G,, Gil  R R,, Alvares  C I,, Patrito  L C,, Genti-Raimondi  S,, Flury  A.. A novel activity for a group of sesquiterpene lactones: Inhibition of aromatase.  FEBS Letters. 1997;;  409 369-400
    PubMedGoogle Scholar
  • 5 Rodriguez  E., Towers  G HN,, Mitchell  J C.. Review - Biological activities of sesquiterpene lactones.  Phytochemistry. 1976;;  15 1573-80
    CrossrefPubMedGoogle Scholar
  • 6 Smith  C H,, Larmer  J,, Thomas  A M,, Kupchan  S M.. Inactivation of glycogen synthase by the tumor inhibitor verolepin.  Biochimica et Biophysica Acta. 1972;;  276 94-104
    PubMedGoogle Scholar
  • 7 Page  J D,, Chaney  S G,, Hall  I H,, Lee  K H,, Holbrook  D J.. Inhibition of inosine monophosphate dehydrogenase by sesquiterpene lactones.  Biochimica et Biophysica Acta. 1987;;  926 186-94
    PubMedGoogle Scholar
  • 8 Williams Jr  W L,, Hall  I H,, Grippo  A A,, Oswald  C B,, Lee  K H,, Holbrook  D J,, Chaney  S G.. Inhibition of nucleic acid synthesis in P-388 lymphocytic leukemia tumor cells by helenalin and bis(helenalinyl)malonate in vivo.  Journal of Pharmaceutical Sciences. 1988;;  77 178-84
    PubMedGoogle Scholar
  • 9 Jodynis-Liebert  J,, Murias  M,, Błoszyk  E.. Effect of several sesquiterpene lactones on lipid peroxidation and glutathione level.  Planta Medica. 1999;;  65 320-4
    Article in Thieme ConnectPubMedGoogle Scholar
  • 10 Schmidt  T J.. Helenanolide-type sesquiterpene lactones - III. Rates and stereochemistry in the reaction of helenalin and related helenanolides with sulfhydryl containing biomolecules.  Bioorganic and Medicinal Chemistry. 1997;;  5 645-53
    PubMedGoogle Scholar
  • 11 Chapman  D E,, Holbrook  D J,, Chaney  S G,, Hall  I H,, Lee  K H.. In vitro inhibition of mouse hepatic mixed-function oxidase enzymes by Helenalin and alantolactone.  Biochemical Pharmacology. 1989;;  38 3913-23
    CrossrefPubMedGoogle Scholar
  • 12 Chapman  D E,, Roberts  G B,, Reynolds  D J,, Grippo  A A,, Holbrook  D J,, Hall  I H, et al.. Acute toxicity of helenalin in BDF1 mice.  Fundamental and Applied Toxicology. 1988;;  10 302-12
    CrossrefPubMedGoogle Scholar
  • 13 Mohandas  J,, Marshal  J J,, Duggin  G G,, Horvath  J S,, Tiller  D J.. Low activities of glutathione-related enzymes as factors in the genesis of urinary bladder cancer.  Cancer Research. 1984;;  44 5086-91
    PubMedGoogle Scholar
  • 14 Beers  R F,, Sizer  I W.. A spectrophotometric method for measuring the breakdown of hydrogen peroxide by catalase.  Journal of Biological Chemistry. 1952;;  195 133-40
    PubMedGoogle Scholar
  • 15 Sun  M,, Zigman  S.. An improved spectrophotometric assay for superoxide dismutase based on epinephrine autoxidation.  Analytical Biochemistry. 1978;;  90 81-9
    CrossrefPubMedGoogle Scholar
  • 16 Pedemonte  J,, Olate  J,, Cerventes  J,, Oberti  C,, Gil  L.. Alterations in mouse liver monooxygenases by benzothiadiazoles.  Biochemical Pharmacology. 1981;;  30 1483-95
    CrossrefPubMedGoogle Scholar
  • 17 Bourrie  M,, Meunier  V,, Berger  Y,, Fabre  G.. Cytochrome P450 isoform inhibitors as a tool for the investigation of metabolic reactions catalyzed by human liver microsomes.  Journal of Pharmacology and Experimental Therapy. 1996;;  227 321-32
    PubMedGoogle Scholar
  • 18 Parkinson  A.. Biotransformation of xenobiotics. In: Classen CD, editor Casarett and Doull's Toxicology. The basic acience of poisons. Mc Graw-Hill; 1995: 113-86
    Google Scholar
  • 19 Sun  Yi.. Free radicals, antioxidant enzymes, and carcinogenesis.  Free radical biology and medicine. 1990;;  8 583-99
    CrossrefPubMedGoogle Scholar
  • 20 Bast  A,, Haenen  G RMM.. Cytochrome P-450 and glutathione: What is significance of their interrelationship in lipid peroxidation.  Trends in Biochemical Sciences. 1984;;  9 510-3
    CrossrefPubMedGoogle Scholar
  • 21 Goligorsky  M S,, Morgan  M A,, Lyubsky  S,, Gross  W R,, Adams  D T,, Spitz  D R.. Establishment of a hydrogen peroxide resistant variant of renal tubular epithelial cells: Role of calcium-independent phospholipase A2 in cell damage.  Archives of Biochemistry and Biophysics. 1993;;  301 119-28
    CrossrefPubMedGoogle Scholar
  • 22 Junqueira  V BC,, Koch  O R,, Arisi  A KM,, Fuzaro  A P,, Azzalis  L A,, Barros  S BM, et al.. Regression of morphological alterations and oxidative stress-related parameters after acute lindane-induced hepatotoxicity in rats.  Toxicology. 1997;;  117 199-205
    CrossrefPubMedGoogle Scholar
  • 23 Choudhary  D,, Chandra  D,, Kale  R K.. Influence of methylglyoxal on antioxidant enzymes and oxidative damage.  Toxicology Letters. 1997;;  93 141-52
    CrossrefPubMedGoogle Scholar
  • 24 Salovsky  P,, Shopova  V,, Dancheva  V.. Antioxidant defense mechanism in the lung toxicity of tri-n-butyl phosphate.  American Journal of Industrial Medicine. 1998;;  33 11-5
    CrossrefPubMedGoogle Scholar
  • 25 Sodhi  C P,, Rana  S F,, Attri  S,, Mehta  S,, Yaiphei  K,, Mehta  S K.. Oxidative-hepatic injury of isoniazid - rifampicin in young rats subjected to protein and energy malnutrition.  Drug and Chemical Toxicology. 1998;;  21 305-17
    PubMedGoogle Scholar
  • 26 Skrzydlewska  E,, Farbiszewski  R.. Decreased antioxidant defense mechanism in rat liver after methanol intoxication.  Free Radical Research. 1997;;  27 369-75
    PubMedGoogle Scholar
  • 27 Arumugam  N,, Sivakumar  V,, Thanislass  J,, Devaraj  H.. Effect of acroleine on rat liver antioxidant defense system.  Indian Journal of Experimental Biology. 1997;;  35 1373-4
    PubMedGoogle Scholar
  • 28 Magwere  T,, Naik  Y S,, Hasler  J A.. Primaquine alters antioxidant enzyme profiles in rat liver and kidney.  Free Radical Research. 1997;;  27 173-9
    PubMedGoogle Scholar
  • 29 Holowska  K,, Lenartova  V,, Rosival  J,, Kicinkova  M,, Majerciakova  A,, Legath  J.. Antioxidant and detoxifying enzymes in the liver of pheasants after intoxication by herbicides MCPA and ANITENT.  Journal of Biochemical and Molecular Toxicology. 1998;;  12 235-44
    CrossrefPubMedGoogle Scholar
  • 30 Harris  E D.. Regulation of antioxidant enzymes.  FASEB Journal. 1992;;  6 2675-83
    PubMedGoogle Scholar
  • 31 Gnojkowski  J,, Baer-Dubowska  W,, Klimek  D,, Chmiel  J.. Effect of toluidines on drug metabolizing enzymes in rat liver, kidney and lung.  Toxicology. 1984;;  32 335-42
    CrossrefPubMedGoogle Scholar
  • 32 Heiskanen  K,, Lindstöm-Seppä  P,, Haataja  L,, Vaittinen  L-H,, Vertiainen  T,, Komulainen  H.. Altered enzyme activities of xenobiotic biotransformation in kidneys after subchronic administration of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) to Rats.  Toxicology. 1995;;  100 121-8
    CrossrefPubMedGoogle Scholar

Dr. J. Jodynis-Liebert

Department of Toxicology Karol Marcinkowski University of Medical Sciences

Dojazd 30

60-631 Poznań

Poland

Email: liebert@usoms.poznan.pl

Phone: +48 61 847 07 21

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