Environmental Analysis Health and Toxicology

The Korean Society of Environmental Health and Toxicology (환경독성보건학회)
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Hepatic Expression of Drug Metabolizing Enzyme in Diabetes

당뇨병에서 간의 약물대사효소 발현변화

  • Oh, Jung-Min (College of Pharmacy and Research Center for Transgenic Cloned Pigs, Chungnam National University) ;
  • Kim, Bong-Hee (College of Pharmacy and Research Center for Transgenic Cloned Pigs, Chungnam National University)
  • 오정민 (충남대학교 약학대학 및 형질전환복제돼지센터) ;
  • 김봉희 (충남대학교 약학대학 및 형질전환복제돼지센터)
  • Published : 2008.09.30
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Abstract

간의 약물대사는 흡수된 외인성물질의 배설을 위한 중추적인 역할을 수행하면 이 반응은 일상대사와 이상대사효소로 구성된 약물대사효소계에 의해 매개된다. 약물대사효소의 발현과 활성은 외인성물질의 노출에 의해 유도되거나 억제되며 이 결과는 약물상호작용을 발생시키는 주요한 원인이다. 또한 당뇨, 비만, 영양실조, 음주, 염증반응 등의 병적인 생리상태는 간에서 약물대사효소의 발현과 활성을 조절하는 것으로 보고되고 있다. 이러한 변동은 치료약물 또는 환경오염물질에 대한 인체의 반응성에 영향을 미치며 결과적으로 예측하지 못한 부작용이나 독성을 발생시킬 수 있다. 본 논문에서는 당뇨병에서 약물대사효소의 발현변화를 정리하였다.

Keywords

References

  1. Abernethy DR, Greenblatt DJ, Divoll M and Shader RI. Enhanced glucuronide conjugation of drugs in obesity: studies of lorazepam, oxazepam, and acetaminophen, J Lab Clin Med 1983; 101: 873-880
  2. Agius C and Gidari AS. Effect of streptozotocin on the glutathione S-transferases of mouse liver cytosol, Biochem Pharmacol 1985; 34: 811-819 https://doi.org/10.1016/0006-2952(85)90761-0
  3. Badger TM, Ronis MJ, Lumpkin CK, Valentine CR, Shahare M, Irby D, Huang J, Mercado C, Thomas P, Ingelman- Sundberg M. and Crouch J. Effects of chronic ethanol on growth hormone secretion and hepatic cytochrome P450 isozymes of the rat, J Pharmacol Exp Ther 1993; 264: 438-447
  4. Barnett CR, Gibson GG, Wolf CR, Flatt PR and Ioannides C. Induction of cytochrome P450III and P450IV family proteins in streptozotocin-induced diabetes, Biochem J 1990; 268: 765-769 https://doi.org/10.1042/bj2680765
  5. Bellward GD, Chang T, Rodrigues B, McNeill JH, Maines S, Ryan DE, Levin W and Thomas PE. Hepatic cytochrome P-450j induction in the spontaneously diabetic BB rat, Mol Pharmacol 1988; 33: 140-143
  6. Braun L, Coffey MJ, Puskas F, Kardon T, Nagy G, Conley AA, Burchell B and Mandl J. Molecular basis of bilirubin UDP-glucuronosyltransferase induction in spontaneously diabetic rats, acetone-treated rats and starved rats, Biochem J 1988; 336: 587-592
  7. Chaudhary IP, Tuntaterdtum S, McNamara PJ, Robertson LW and Blouin RA. Effect of genetic obesity and phenobarbital treatment on the hepatic conjugation pathways, J Pharmacol Exp Ther 1993; 265: 1333-1338
  8. Cherrington AD. Banting Lecture 1997. Control of glucose uptake and release by the liver in vivo, Diabetes 1999; 48: 1198-1214 https://doi.org/10.2337/diabetes.48.5.1198
  9. Clarke J, Snelling J, Ioannides C, Flatt PR and Barnett CR. Effect of vitamin C supplementation on hepatic cytochrome P450 mixed-function oxidase activity in streptozotocin- diabetic rats, Toxicol Lett 1996; 89: 249-256 https://doi.org/10.1016/S0378-4274(96)03822-2
  10. Constantopoulos A and Matsaniotis N. Augmentation of uridine diphosphate glucuronyltransferase activity in rat liver by adenosine 3,5′-monophosphate, Gastroenterology 1978; 75: 486-491
  11. Cowpland C, Su GM, Murray M, Puddey IB and Croft KD. Effect of alcohol on cytochrome p450 arachidonic acid metabolism and blood pressure in rats and its modulation by red wine polyphenolics, Clin Exp Pharmacol Physiol 2006; 33: 183-188 https://doi.org/10.1111/j.1440-1681.2006.04337.x
  12. Davila JA, Morgan RO, Shaib Y, McGlynn KA and El- Serag HB. Diabetes increases the risk of hepatocellular carcinoma in the United States: a population based case control study, Gut 2005; 54: 533-539 https://doi.org/10.1136/gut.2004.052167
  13. De Waziers I, Garlatti M, Bouguet J, Beaune PH and Barouki R. Insulin down-regulates cytochrome P450 2B and 2E expression at the post-transcriptional level in the rat hepatoma cell line, Mol Pharmacol 1995; 47: 474-479
  14. Donahue BS, Skottner-Lundin A and Morgan ET. Growth hormone-dependent and -independent regulation of cytochrome P-450 isozyme expression in streptozotocindiabetic rats, Endocrinology 1991; 128: 2065-2076 https://doi.org/10.1210/endo-128-4-2065
  15. Dong Z, Hong J, Ma Q, Li D, Bullock J, Gonzalez FJ, Park SS, Gelboin HV and Yang CS. Mechanism of induction of cytochrome P450ac (P450j) in chemically induced and spontaneously diabetic rats, Arch Biochem Biophys 1988; 263: 29-35 https://doi.org/10.1016/0003-9861(88)90610-8
  16. Duvaldestin P, Mahu J-L and Berthelot P. Effect of fasting on substrate specificity of rat liver UDP-glucuronosyltransferase, Biochim Biophys Acta 1975; 384: 81-86 https://doi.org/10.1016/0005-2744(75)90097-2
  17. Grant MH and Duthie SJ. Conjugation reactions in hepatocytes isolated from streptozotocin-induced diabetic rats, Biochem Pharmacol 1987; 36: 3647-3655 https://doi.org/10.1016/0006-2952(87)90015-3
  18. Hong JY, Pan JM, Gonzalez FJ, Gelboin HV and Yang CS. The induction of a specific form of cytochrome P-450 (P-450j) by fasting, Biochem Biophys Res Commun 1987; 142: 1077-1083 https://doi.org/10.1016/0006-291X(87)91525-7
  19. Irizar A, Barnett CR, Flatt PR and Ioannides C. Defective expression of cytochrome P450 proteins in the liver of the genetically obese Zucker rat, Eur J Pharmacol 1995; 293: 385-393 https://doi.org/10.1016/S0014-2999(95)80097-2
  20. Kang KW, Cho MK, Lee CH and Kim SG. Activation of phosphatidylinositol 3-kinase and Akt by tert-butylhydroquinone is responsible for antioxidant response element- mediated rGSTA2 induction in H4IIE cells, Mol Pharmacol 2001; 59: 1147-1156 https://doi.org/10.1124/mol.59.5.1147
  21. Kardon T, Coffey MJ, Banhegyi G, Conley AA, Burchell B, Mandl J and Braun L. Transcriptional induction of bilirubin UDP-glucuronosyltransrase by ethanol in rat liver, Alcohol 2000; 21: 251-257 https://doi.org/10.1016/S0741-8329(00)00095-1
  22. Kim MS, Wang S, Shen Z, Kochansky CJ, Strauss JR, Franklin RB and Vincent SH. Differences in the pharmacokinetics of peroxisome proliferator-activated receptor agonists in genetically obese Zucker and sprague-dawley rats: implications of decreased glucuronidation in obese Zucker rats, Drug Metab Dispos 2004; 32: 909-914
  23. Kim SK and Novak RF. The role of intracellular signaling in insulin-mediated regulation of drug metabolizing enzyme gene and protein expression, Pharmacol Ther 2007; 113: 88-120 https://doi.org/10.1016/j.pharmthera.2006.07.004
  24. Kim SK, Woodcroft KJ and Novak RF. Insulin and glucagon regulation of glutathione S-transferase expression in primary cultured rat hepatocytes, J Pharmacol Exp Ther 2003a; 305: 353-361 https://doi.org/10.1124/jpet.102.045153
  25. Kim SK, Woodcroft KJ, Kim SG and Novak RF. Insulin and glucagon signaling in regulation of microsomal epoxide hydrolase expression in primary cultured rat hepatocytes, Drug Metab Dispos 2003b; 31: 1260-1268 https://doi.org/10.1124/dmd.31.10.1260
  26. Kim SK, Woodcroft KJ and Novak RF. Insulin and growth factor signaling in Drug Metabolism and Transport (Lash, L.H., Ed.). Humana Press, Totowa, 2005: pp. 49-83
  27. Leclercq IA, Farrell GC, Field J, Bell DR, Gonzalez FJ and Robertson GR. CYP2E1 and CYP4A as microsomal catalysts of lipid peroxides in murine nonalcoholic steatohepatitis, J Clin Invest 2000; 105: 1067-1075 https://doi.org/10.1172/JCI8814
  28. Lieber CS. Cytochrome P-4502E1: its physiological and pathological role, Physiol Rev 1997; 77: 517-544 https://doi.org/10.1152/physrev.1997.77.2.517
  29. Lu SC, Huang ZZ, Yang JM and Tsukamoto H. Effect of ethanol and high-fat feeding on hepatic gamma-glutamylcysteine synthetase subunit expression in the rat, Hepatology 1999; 30: 209-214 https://doi.org/10.1002/hep.510300134
  30. Mukherjee B, Mukherjee JR and Chatterjee M. Lipid peroxidation, glutathione levels and changes in glutathionerelated enzyme activities in streptozotocin-induced diabetic rats, Immunol Cell Biol 1994; 72: 109-114 https://doi.org/10.1038/icb.1994.17
  31. Raucy JL, Lasker JM, Kraner JC, Salazar DE, Lieber CS and Corcoran GB. Induction of cytochrome P450IIE1 in the obese overfed rat, Mol Pharmacol 1991; 39: 275-280
  32. Raza H, Ahmed I, Lakhani MS, Sharma AK, Pallot D and Monague W. Effect of bitter melon (Momordica charantia) fruit juice on the hepatic cytochrome P450-dependent monooxygenases and glutathione S-transferases in streptozotocin-induced diabetic rats, Biochem Pharmacol 1996; 52: 1639-1642 https://doi.org/10.1016/S0006-2952(96)00526-6
  33. Roe AL, Howard G, Blouin R and Snawder JE. Characterization of cytochrome P450 and glutathione S-transferase activity and expression in male and female ob/ob mice, Int J Obes Relat Metab Disord 1999; 23: 48-53 https://doi.org/10.1038/sj.ijo.0800756
  34. Rouer E, Mahu JL, Dansette P and Leroux JP. UDP-glucuronosyltransferase, epoxide hydrolase and glutathione S-transferase activities in the liver of diabetic mice, Biochim Biophys Acta 1981; 676: 274-277 https://doi.org/10.1016/0304-4165(81)90197-5
  35. Rubin E and Lieber CS. Hepatic microsomal enzymes in man and rat: induction and inhibition by ethanol, Science 1968; 162: 690-691 https://doi.org/10.1126/science.162.3854.690
  36. Runge-Morris M and Vento C. Effects of streptozotocininduced diabetes on rat liver sulfotransferase gene expression, Drug Metab Dispos 1995; 23: 455-459
  37. Sanyal AJ. Mechanisms of Disease: pathogenesis of nonalcoholic fatty liver disease, Nat Clin Pract Gastroenterol Hepatol 2005; 2: 46-53 https://doi.org/10.1038/ncpgasthep0084
  38. Shimojo N, Ishizaki T, Imaoka S, Funae Y, Fujii S and Okuda K. Changes in amounts of cytochrome P450 isozymes and levels of catalytic activities in hepatic and renal microsomes of rats with streptozocin-induced diabetes, Biochem Pharmacol 1993; 46: 621-627 https://doi.org/10.1016/0006-2952(93)90547-A
  39. Song BJ, Veech RL and Saenger P. Cytochrome P450IIE1 is elevated in lymphocytes from poorly controlled insulin- dependent diabetics, J Clin Endocrinol Metab 1990; 71: 1036-1040 https://doi.org/10.1210/jcem-71-4-1036
  40. Thomas H, Schladt L, Knehr M and Oesch F. Effect of diabetes and starvation on the activity of rat liver epoxide hydrolases, glutathione S-transferases and peroxisomal beta-oxidation, Biochem Pharmacol 1989; 38:4291-4297 https://doi.org/10.1016/0006-2952(89)90528-5
  41. Tunon MJ, Gonzalez P, Garcia-Pardo LA and Gonzalez J. Hepatic transport of bilirubin in rats with streptozotocininduced diabetes, J Hepatol 1991; 13: 71-77 https://doi.org/10.1016/0168-8278(91)90866-A
  42. Van de Wiel JA, Fijneman PH, Teeuw KB, Van Ommen B, Noordhoek J and Bos RP. Influence of long-term ethanol treatment on rat liver biotransformation enzymes, Alcohol 1993; 10: 397-402 https://doi.org/10.1016/0741-8329(93)90027-L
  43. Videla LA, Rodrigo R, Araya J and Poniachik J. Oxidative stress and depletion of hepatic long-chain polyunsaturated fatty acids may contribute to nonalcoholic fatty liver disease, Free Radic Biol Med 2004a; 37: 1499-1507 https://doi.org/10.1016/j.freeradbiomed.2004.06.033
  44. Videla LA, Rodrigo R, Orellana M, Fernandez V, Tapia G, Quinones L, Varela N, Contreras J, Lazarte R, Csendes A, Rojas J, Maluenda F, Burdiles P, Diaz JC, Smok G, Thielemann L and Poniachik J. Oxidative stress-related parameters in the liver of non-alcoholic fatty liver disease patients, Clin Sci (Lond) 2004b; 106: 261-268 https://doi.org/10.1042/CS20030285
  45. Visser TJ, van Haasteren GA, Linkels E, Kaptein E, van Toor H and de Greef WJ. Gender-specific changes in thyroid hormone-glucuronidating enzymes in rat liver during short-term fasting and long-term food restriction, Eur J Endocrinol 1996; 135: 489-497 https://doi.org/10.1530/eje.0.1350489
  46. Wasserman WW and Fahl WE. Functional antioxidant responsive elements, Proc Natl Acad Sci USA 1997; 94: 5361-5366 https://doi.org/10.1073/pnas.94.10.5361
  47. Woodcroft KJ, Hafner MS and Novak RF. Insulin signaling in the transcriptional and posttranscriptional regulation of CYP2E1 expression, Hepatology 2002; 35: 263-273 https://doi.org/10.1053/jhep.2002.30691
  48. Xiong H, Yoshinari K, Brouwer KL and Negishi M. Role of constitutive androstane receptor in the in vivo induction of Mrp3 and CYP2B1/2 by phenobarbital, Drug Metab Dispos 2002; 30: 918-923 https://doi.org/10.1124/dmd.30.8.918
  49. Yamazoe Y, Murayama N, Shimada M, Yamauchi K and Kato R. Cytochrome P450 in livers of diabetic rats: Regulation by growth hormone and insulin, Arch Biochem Biophys 1989a; 268: 567-575 https://doi.org/10.1016/0003-9861(89)90324-X
  50. Yamazoe Y, Murayama N, Shimada M, Imaoka S, Funae Y and Kato R. Suppression of hepatic levels of an ethanolinducible P-450DM/j by growth hormone: relationship between the increased level of P-450DM/j and depletion of growth hormone in diabetes, Mol Pharmacol 1989b; 36: 716-722
  51. Yoshida K, Hirokawa J, Tagami S, Kawakami Y, Urata Y and Kondo T. Weakened cellular scavenging activity against oxidative stress in diabetes mellitus: regulation of glutathione synthesis and efflux, Diabetologia 1995; 38: 201-210 https://doi.org/10.1007/BF00400095
  52. Yoshinari K, Takagi S, Sugatani J and Miwa M. Changes in the expression of cytochromes P450 and nuclear receptors in the liver of genetically diabetic db/db mice, Biol Pharm Bull 2006a; 29: 1634-1638 https://doi.org/10.1248/bpb.29.1634
  53. Yoshinari K, Takagi S, Yoshimasa T, Sugatani J and Miwa M. Hepatic CYP3A expression is attenuated in obese mice fed a high-fat diet, Pharm Res 2006b; 23: 1188-1200 https://doi.org/10.1007/s11095-006-0071-6