[go: up one dir, main page]

Skip to content
Licensed Unlicensed Requires Authentication Published by De Gruyter July 2, 2016

Age-dependent features of CYP3A, CYP2C, and CYP2E1 functioning at metabolic syndrome

  • Larysa B. Bondarenko EMAIL logo , Ganna M. Shayakhmetova , Alla K. Voronina and Valentina M. Kovalenko

Abstract

Background:

Complex investigations of cytochrome P450 (CYP) isoforms with metabolic syndrome (MS) development are limited, and specific features of adolescent’s metabolisms are generally disregarded. The aim of present study was a comparative estimation of MS-mediated changes in CYP3A, CYP2C, and CYP2E1 mRNA expression and enzymatic activities, as well as antioxidant system parameters of adult and pubertal rats.

Methods:

Wistar albino male rats of two age categories [young animals of 21 days age (50–70 g) and adults (160–180 g)] were divided into four groups (eight animals in each group): (1) control 1 (intact young rats), (2) control 2 (intact adult rats), (3) MS3 (young rats with MS), and (4) MS4 (adult rats with MS). The MS was induced by full replacement of drinking water by 20% fructose solution (200 g/L). After 60 days of MS modeling, the investigation of rat liver CYP3A, CYP2C, and CYP2E1 mRNA expressions, their enzyme-marker activities, as well as the antioxidant system parameters was conducted.

Results:

Levels of liver CYP2E1 mRNA expression increased with MS: 40% (adults) and 80% (pubertal rats). Pubertal rats had also increased CYP3A2 mRNA expression (30%) and decreased CYP2C mRNA expression (30%). Changes in CYP2E1 and CYP2C enzymatic activities were consistent with the changes of corresponding gene expressions at both age-groups with MS. Simultaneously, liver reduced glutathione contents, and glutathione transferase and reductase activities were decreased in pubertal animals.

Conclusions:

CYP isoform expression rates and glutathione system were greatly violated with MS. The greater changes were observed in pubertal rats with MS.

  1. Author contributions:All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: None declared.

  3. Employment or leadership:None declared.

  4. Honorarium: None declared.

  5. Competing interests:The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

References

1. Strolin Benedetti M, Whomsley R, Baltes EL. Differences in absorption, distribution, metabolism and excretion of xenobiotics between the paediatric and adult populations. Expert Opin Drug Metab Toxicol 2005;1:447–71.10.1517/17425255.1.3.447Search in Google Scholar

2. Burke V, Beilin LJ, Simmer K, Oddy WH, Blake KV, Doherty D, et al. Predictors of body mass index and associations with cardiovascular risk factors in Australian children: a prospective cohort study. Int J Obes (Lond) 2005;29:15–23.10.1038/sj.ijo.0802750Search in Google Scholar

3. Misra A, Khurana L. The metabolic syndrome in South Asians: epidemiology, clinical correlates and possible solutions. Int Diabetes Monitor 2009;21:92–101.Search in Google Scholar

4. Bondarenko L, Karatzuba T, Shayakhmetova G, Voronina A, Matvienko A, Strelkov IE, et al. Specificity of metabolic syndrome model reproduction at pubertal and adult male rats. Rom J Diabetes Nutr Metab Dis 2015;22:251–60.10.1515/rjdnmd-2015-0031Search in Google Scholar

5. Abdulla MH, Sattar MA, Abdullah NA, Hye Khan MA, Anand Swarup KR, Johns EJ. The contribution of α1B-adrenoreceptor subtype in the renal vasculature of fructose-fed Sprague-Dawley rats. Eur J Nutr 2011;50:251–60.10.1007/s00394-010-0133-8Search in Google Scholar

6. Kamath SA, Kummerow FA, Narayan KA. A simple method for the isolation of rat liver microsomes. FEBS Lett 1971;17:90–2.10.1016/0014-5793(71)80571-9Search in Google Scholar

7. Omura T, Sato R. The carbon monoxide-binding pigment of liver microsomes. J Biol Chem 1964;239:2370–85.10.1016/S0021-9258(20)82244-3Search in Google Scholar

8. Koop DR. Inhibition of ethanol-inducible cytochrome P-450 2E1 by 3-amino-1,2,4-triazole. Chem Res Toxicol 1990;3:377–8310.1021/tx00016a017Search in Google Scholar

9. Jager W, Correia MA, Bornheim LM, Mahnke A, Hanstein WG, Xue L, et al. Ethynilestradiol-mediated induction of hepatic CYP3A9 in female rats: implication for cyclosporine metabolism. Drug Мetab Dispos 1999;27:1505–11.Search in Google Scholar

10. Imaoka S, Hashizume T, Funae Y. Localization of rat cytochrome P450 in various tissues and comparison of arachidonic acid metabolism by rat P450 with that by human P450 orthologs. Drug Metab Pharmaсokinet 2005;20:478–84.10.2133/dmpk.20.478Search in Google Scholar

11. Wang RW, Newton DJ, Scheri TD, Lu AY. Human cytochrome P450 3A4-catalyzed testosterone 6β-hydroxylation and erythromycin N-demethylation. Drug Metab Dispos 1997;25:502–7.Search in Google Scholar

12. Nekrasova LV, Russkih YaV, Novikov AV, Krasnov NV, Zhakovskaya ZA. Application of the method (HPLC-tandem high resolution MS) for the drug compounds determination in natural water. Scientific Instrumentation [Nauchnoye priborostroenie] 2010;20:59–66. [Rus].Search in Google Scholar

13. Habig WH, Pabst MJ, Jakoby WB. Glutathione-S-transferases. J Biol Chem 1974;249:7130–9.10.1016/S0021-9258(19)42083-8Search in Google Scholar

14. Costa LG, Hodgson E, Lawrence DA, Ozolins TR, Reed DJ, Greenlee WF, editors. Current protocols in toxicology. New York: John Wiley & Sons, Inc., 2005:2759.Search in Google Scholar

15. Sedlak J, Lindsay R. Estimation of total, protein-bound and nonprotein sulfhydryl groups in tissue with Ellman’s reagent. Anal Biochem 1968;25:192–205.10.1016/0003-2697(68)90092-4Search in Google Scholar

16. Lankford SM, Bai SA, Goldstein JA. Cloning of canine cytochrome P-450 2E1 cDNA: identification and characterization of two variant alleles. Drug Metab Dispos 2000;28:981–6.Search in Google Scholar

17. Taavistsainen P. Cytochrome P450 isoform specific in vitro methods to predict drug metabolism and interactions. Oulu: Oulu University Press, 2001. Available from: http://herkules.oulu.fi/issn03553221/.Search in Google Scholar

18. Lucas D, Farez C, Bardou LG, Vaisse J, Attali JR, Valensi P. Cythochrome P-450 2E1 activity in diabetic and obese patients as assessed by chlorzoxazone hydroxylation. Fundam Clin Pharmacol 1998;12:553–8.10.1111/j.1472-8206.1998.tb00985.xSearch in Google Scholar PubMed

19. Dey A, Cederbaum AI. Induction of cytochrome P-450 2E1 promotes liver injury in ob/ob mice. Hepathology 2007;45:1355–65.10.1002/hep.21603Search in Google Scholar PubMed

20. Oesterheld JR. A review of developmental aspects of cytochrome P450. J Child Adolesc Psychopharmacol 1998;8:161–74.10.1089/cap.1998.8.161Search in Google Scholar PubMed

21. Yang MX, Cederbaum AI. Glycerol increases content and activity of human cytochrome P-4502E1 in a transduced HepG2 cell line by protein stabilization. Alcohol Clin Exp Res 1997;21:340–7.10.1111/j.1530-0277.1997.tb03770.xSearch in Google Scholar

22. Tain YL, Wu KL, Lee WC, Leu S, Chan JY. Maternal fructose-intake-induced renal programming in adult male offspring. J Nutr Biochem 2015;26:642–50.10.1016/j.jnutbio.2014.12.017Search in Google Scholar PubMed

23. Lupp A, Karge E, Deufel T, Oelschlägers H, Fleck C. Ciprofibrate, clofibric acid and respective glycinate derivatives. Effects of a four-week treatment on male lean and obese Zucker rats. Arzneimittelforschung 2008;58:225–41.10.1055/s-0031-1296499Search in Google Scholar PubMed

24. Zong H, Armoni M, Harel C, Karnieli E, Pessin JE. Cytochrome P-450 CYP2E1 knockout mice are protected against high-fat diet-induced obesity and insulin resistance. Am J Physiol Endocrinol Metab 2012;302:E532–9.10.1152/ajpendo.00258.2011Search in Google Scholar PubMed PubMed Central

25. Brill MJ, Diepstraten J, van Rongen A, van Kralingen S, van den Anker JN, Knibbe CA. Impact of the obesity on drug metabolism and elimination in adults and children. Clin Pharmacokinet 2012;51:277–304.10.2165/11599410-000000000-00000Search in Google Scholar PubMed

26. Shou M, Dai R, Cui D, Korzekwa KR, Baillie TA, Rushmore TH. A kinetic model for the metabolic interaction of two substrates at the active site of cytochrome P450 3A4. J Biol Chem 2001;276:2256–62.10.1074/jbc.M008799200Search in Google Scholar PubMed

27. Oh SJ, Choi JM, Yun KU, Oh JM, Kwak HC, Oh JG, et al. Hepatic expression of cytochrome P450 in type 2 diabetic Goto-Kakizaki rats. Chem Biol Interact 2012;195:173–9.10.1016/j.cbi.2011.12.010Search in Google Scholar PubMed

28. Zhou S, Yung Chan S, Cher Goh B, Chan E, Duan W, Huang M, et al. Mechanism-based inhibition of cytochrome P450 3A4 by therapeutic drugs. Clin Pharmacokinet 2005;44:279–304.10.2165/00003088-200544030-00005Search in Google Scholar

29. Mayhew BS, Jones DR, Hall SD. An in vitro model for predicting in vivo inhibition of cytochrome P450 3A4 by metabolic intermediate complex formation. Drug Metab Dispos 2000;28:1031–7.Search in Google Scholar

30. Sheweita SA. Drug-metabolizing enzymes: mechanisms and functions. Curr Drug Metab 2000;1:107–32.10.2174/1389200003339117Search in Google Scholar

31. Aguiar M, Masse R. Regulation of cytochrome P450 by posttranslational modification. Drug Metab Rev 2005;37:379–404.10.1081/DMR-46136Search in Google Scholar

32. Jo Corbin C, Mapes SM, Lee YM, Conley AJ. Structural and functional differences among purified recombinant mammalian aromatases: glycosylation, N-terminal sequence and kinetic analysis of human, bovine and the porcine placental and gonadal isozymes. J Mol Cell Endocrinol 2003;206:147–57.10.1016/S0303-7207(02)00422-7Search in Google Scholar

33. Anisimova SI, Shayahmetova HM, Voronina AK, Kovalenko VM. Effect of first rank antitubercular drugs combination on some monooxygenase system indices and antioxidant status of rat liver. Modern Problems of Toxicology 2012;1:16–9. [in Ukrainian].Search in Google Scholar

34. Anisimova SI, Kovalenko VM, Shayahmetova HM, Bondarenko LB, Matvienko AV. The impact of antitubercular drugs to the level of some isoforms of cytochrome P-450 mRNA expression of in rat liver. Pharmacol Drug Toxicol 2012;3:26–31. [in Ukrainian].10.1016/S1201-9712(11)60093-3Search in Google Scholar

35. Li T, Chiang JY. Rifampicin induction of CYP3A4 requires pregnane X receptor cross talk with hepatocyte nuclear factor 4alpha and coactivators, and suppression of small heterodimer partner gene expression. Drug Metab Dispos 2006;34:756–64.10.1124/dmd.105.007575Search in Google Scholar PubMed PubMed Central

36. Wen X, Wang JS, Neuvonen PJ, Backman JT. Isoniazid is a mechanism-based inhibitor of cytochrome P450 1A2, 2A6, 2C19 and 3A4 isoforms in human liver microsomes. Eur J Clin Pharmacol 2002;57:799–804.10.1007/s00228-001-0396-3Search in Google Scholar PubMed

37. Kajosaari LI, Laitila J, Neuvonen PJ, Backman JT. Metabolism of repaglinide by CYP2C8 and CYP3A4 in vitro: effect of fibrates and rifampicin. Basic Clin Pharmacol Toxicol 2005;97:249–56.10.1111/j.1742-7843.2005.pto_157.xSearch in Google Scholar PubMed

38. Roytberh HE, editor. Metabolic syndrome. Moscow: MED-press-inform, 2007:224. [in Russian].Search in Google Scholar

39. Montero D, Walther G, Perez‐Martin A, Roche E, Vinet A. Endothelial dysfunction, inflammation, and oxidative stress in obese children and adolescents: markers and effect of lifestyle intervention. Obes Rev 2012;13:441–55.10.1111/j.1467-789X.2011.00956.xSearch in Google Scholar PubMed

40. Hutcheson R, Rocic P. The metabolic syndrome, oxidative stress, environment, and cardiovascular disease: the great exploration. Exp Diabetes Res 2012;2012:271028.10.1155/2012/271028Search in Google Scholar PubMed PubMed Central

41. Barnett CR, Abbott RA, Bailey CJ, Flatt PR, Ioannides C. Cytochrome P450-dependent mixed-function oxidase and glutathione S-transferase activities in spontaneous obesity-diabetes. Biochem Pharmacol 1992;43:1868–71.10.1016/0006-2952(92)90724-WSearch in Google Scholar

Received: 2016-2-3
Accepted: 2016-5-4
Published Online: 2016-7-2
Published in Print: 2016-11-1

©2016 Walter de Gruyter GmbH, Berlin/Boston

Downloaded on 15.9.2024 from https://www.degruyter.com/document/doi/10.1515/jbcpp-2016-0012/html
Scroll to top button