DOI QR코드

DOI QR Code

Edible mushroom (Pleurotus cornucopiae) extract vs. glibenclamide on alloxan induced diabetes: sub-acute in vivo study of Nrf2 expression and renal toxicity

  • Chinedu Godwin Uzomba (Department of Anatomy, Faculty of Basic Medical Sciences, College of Medical Sciences, Alex Ekwueme Federal University Ndufu-Alike) ;
  • Uchenna Kenneth Ezemagu (Department of Anatomy, Faculty of Basic Medical Sciences, College of Medical Sciences, Alex Ekwueme Federal University Ndufu-Alike) ;
  • Mary-Sonia Ofoegbu (Department of Anatomy, Faculty of Basic Medical Sciences, College of Medical Sciences, Alex Ekwueme Federal University Ndufu-Alike) ;
  • Njoku Lydia (Department of Anatomy, Faculty of Basic Medical Sciences, College of Medical Sciences, Alex Ekwueme Federal University Ndufu-Alike) ;
  • Essien Goodness (Department of Anatomy, Faculty of Basic Medical Sciences, College of Medical Sciences, Alex Ekwueme Federal University Ndufu-Alike) ;
  • Chinedum Emelike (Department of Physiology, Faculty of Basic Medical Sciences, College of Medical Sciences, Alex Ekwueme Federal University Ndufu-Alike) ;
  • Uchewa Obinna (Department of Anatomy, Faculty of Basic Medical Sciences, College of Medical Sciences, Alex Ekwueme Federal University Ndufu-Alike) ;
  • Alo Joseph Nwafor (Department of Anatomy, Faculty of Basic Medical Sciences, College of Medical Sciences, Alex Ekwueme Federal University Ndufu-Alike) ;
  • Ejikeme Felix Mbajiorgu (Department of Histology and Embryology, School of Anatomical Sciences, Faculty of Health Sciences, University of the Witwatersrand)
  • 투고 : 2024.02.26
  • 심사 : 2024.05.07
  • 발행 : 2024.09.30

초록

The study aims to compare the action of Pleurotus cornucopiae and glibenclamide on alloxan-induced diabetes and ascertain how an aqueous extract of the edible mushroom regulates the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), oxidative stress biomarkers and renal toxicity in a diabetic male Wistar rat model. Twenty-five adult male Wistar rats were randomly grouped into five groups with five rats per. Group 1 and those in the treatment groups received normal feed and water ad libitum. Group 2 received intraperitoneal administration of alloxan monohydrate (150 mg/kg body weight). Group 3 received alloxan monohydrate and glibenclamide (5 mg/kg body weight bwt), group 4 received alloxan monohydrate plus the extract (250 mg/kg bwt) and group 5 received alloxan monohydrate plus the extract (500 mg/kg bwt). The administration of glibenclamide plus the extract was oral for 14 days. Glibenclamide and the extract lowered blood glucose level, catalase, and glutathione peroxidase activities, increased the superoxide dismutase (SOD) activity in rats with alloxan induced diabetes. The extract at 500 mg/kg bwt reduced the plasma urea and sodium concentration in the treated rats. The extract and glibenclamide could detoxify alloxan and restore its induced renal degeneration and glomeruli atrophy, intra renal hemorrhage and inflammation and oxidative biomarkers through activation of Nrf2 expression. The drug glibenclamide and P. cornucopiae have appreciable hypoglycemic activity and potential to restore the normal renal architecture in the rats, hence they offer similar curative effects. Additionally, the extract at 500 mg/kg bwt activated SOD and Nrf2 expression more than glibenclamide in rats with alloxan-induced diabetes.

키워드

과제정보

We wish to acknowledge the management team of Animal House in AE-FUNAI and Nnonna Ifeanyi for handling the rats adequately throughout the period of the study.

참고문헌

  1. Sicree R, Shaw J, Zimmet P. The global burden. Diabetes and impaired glucose tolerance. Prevalence and projections. In: Gan D, editor. Diabetes Atlas. 3rd ed. International Diabetes Federation; 2006. p.16-103. 
  2. Owembabazi E, Nkomozepi P, Calvey T, Mbajiorgu EF. Co-administration of alcohol and combination antiretroviral therapy (cART) in male Sprague Dawley rats: a study on testicular morphology, oxidative and cytokines perturbations. Anat Cell Biol 2023;56:236-51.  https://doi.org/10.5115/acb.22.229
  3. Collins AJ, Kasiske B, Herzog C, Chen SC, Everson S, Constantini E, Grimm R, McBean M, Xue J, Chavers B, Matas A, Manning W, Louis T, Pan W, Liu J, Li S, Roberts T, Dalleska F, Snyder J, Ebben J, Frazier E, Sheets D, Johnson R, Li S, Dunning S, Berrini D, Guo H, Solid C, Arko C, Daniels F, Wang X, Forrest B, Gilbertson D, St Peter W, Frederick P, Eggers P, Agodoa L. Excerpts from the United States Renal Data System 2003 annual data report: atlas of end-stage renal disease in the United States. Am J Kidney Dis 2003;42(6 Suppl 5):A5-7, S1-230. 
  4. Church DS, Barker P, Burling KA, Shinwari SK, Kennedy C, Smith D, Macfarlane DP, Kernohan A, Stears A, Karamat MA, Whyte K, Narendran P, Halsall DJ, Semple RK. Diagnosis and treatment of anti-insulin antibody-mediated labile glycaemia in insulin-treated diabetes. Diabet Med 2023;40:e15194. 
  5. Yenet A, Nibret G, Tegegne BA. Challenges to the availability and affordability of essential medicines in African countries: a scoping review. Clinicoecon Outcomes Res 2023;15:443-58.  https://doi.org/10.2147/CEOR.S413546
  6. Ugwu E, Young E, Nkpozi M. Diabetes care knowledge and practice among primary care physicians in Southeast Nigeria: a cross-sectional study. BMC Fam Pract 2020;21:128. 
  7. Ogbera AO, Ekpebegh C. Diabetes mellitus in Nigeria: the past, present and future. World J Diabetes 2014;5:905-11.  https://doi.org/10.4239/wjd.v5.i6.905
  8. Uloko AE, Musa BM, Ramalan MA, Gezawa ID, Puepet FH, Uloko AT, Borodo MM, Sada KB. Prevalence and risk factors for diabetes mellitus in Nigeria: a systematic review and metaanalysis. Diabetes Ther 2018;9:1307-16.  https://doi.org/10.1007/s13300-018-0441-1
  9. Okolo KO, Siminialayi IM, Orisakwe OE. Protective effects of Pleurotus tuber-regium on carbon- tetrachloride induced testicular injury in Sprague Dawley rats. Front Pharmacol 2016;7:480. 
  10. Golak-Siwulska I, Kaluzewicz A, Spizewski T, Siwulski M, Sobieralski K. Bioactive compounds and medicinal properties of Oyster mushrooms (Pleurotus sp.). Folia Hortic 2018;30:191-201.  https://doi.org/10.2478/fhort-2018-0012
  11. Izham I, Avin F, Raseetha S. Systematic review: heat treatments on phenolic content, antioxidant activity, and sensory quality of Malaysian mushroom: oyster (Pleurotus spp.) and black jelly (Auricularia spp.). Front Sustain Food Syst 2022;6:882939. 
  12. Khan MA, Tania M. Nutritional and medicinal importance of Pleurotus mushrooms: an overview. Food Rev Int 2012;28:313-29.  https://doi.org/10.1080/87559129.2011.637267
  13. Joshi M, Sagar A. In vitro free radical scavenging activity of a wild edible mushroom, Sparassis crispa (Wulf.) Fr., from North Western Himalayas, India. J Mycol 2014;2014:748531. 
  14. Wasser SP. Medicinal mushroom science: current perspectives, advances, evidences, and challenges. Biomed J 2014;37:345-56.  https://doi.org/10.4103/2319-4170.138318
  15. Lindequist U, Niedermeyer TH, Julich WD. The pharmacological potential of mushrooms. Evid Based Complement Alternat Med 2005;2:285-99.  https://doi.org/10.1093/ecam/neh107
  16. Guillamon E, Garcia-Lafuente A, Lozano M, D'Arrigo M, Rostagno MA, Villares A, Martinez JA. Edible mushrooms: role in the prevention of cardiovascular diseases. Fitoterapia 2010;81:715-23.  https://doi.org/10.1016/j.fitote.2010.06.005
  17. Farquhar WB, Edwards DG, Jurkovitz CT, Weintraub WS. Dietary sodium and health: more than just blood pressure. J Am Coll Cardiol 2015;65:1042-50.  https://doi.org/10.1016/j.jacc.2014.12.039
  18. Elsayed EA, El Enshasy H, Wadaan MA, Aziz R. Mushrooms: a potential natural source of anti-inflammatory compounds for medical applications. Mediators Inflamm 2014;2014:805841. 
  19. Okolo KO, Orisakwe OE. In vitro antioxidants and hepatoprotective effects of Pleurotus tuber-regium on carbon tetrachloride-treated rats. J Basic Clin Physiol Pharmacol 2020;32:67-78.  https://doi.org/10.1515/jbcpp-2020-0034
  20. Rajasekaran S, Sivagnanam K, Subramanian S. Antioxidant effect of Aloe vera gel extract in streptozotocin-induced diabetes in rats. Pharmacol Rep 2005;57:90-6. 
  21. Gray AM, Flatt PR. Insulin-releasing and insulin-like activity of Agaricus campestris (mushroom). J Endocrinol 1998;157:259-66.  https://doi.org/10.1677/joe.0.1570259
  22. Okigbo RN, Ezebo RO, Nwatu CM, Omumuabuike JN, Esimai GB. A study on cultivation of indigenous mushrooms in South Eastern Nigeria. World News Nat Sci 2021;34:154-64. 
  23. Wang H, Gao J, Ng TB. A new lectin with highly potent anti-hepatoma and antisarcoma activities from the oyster mushroom Pleurotus ostreatus. Biochem Biophys Res Commun 2000;275:810-6.  https://doi.org/10.1006/bbrc.2000.3373
  24. Aloke C, Emelike CU, Obasi NA, Ogbu PN, Edeogu CU, Uzomba GC, Ekakitie O, Iyaniwura, AA, Okoro CC, Okey BP, Aninjoku GG, Ushahemba BC. HPLC profiling and studies on Copaifera salikounda methanol leaf extract on phenylhydrazine-induced hematotoxicity and oxidative stress in rats. Arabian J Chem 2021;14:103428. 
  25. Harborne JB. Phytochemical methods. 3rd ed. Chapman and Hall Ltd; 1993. p. 49-188. 
  26. Adebiyi AO. Distribution of phytochemicals and some antinutrients in selected edible mushrooms in Ekiti State, Nigeria. Int J Sci Eng Invent 2018;2018:10-3. 
  27. Wong F, Chai TT, Tan SL, Yong AL. Evaluation of bioactivities and phenolic content of selected edible mushrooms in Malaysia. Trop J Pharm Res 2013;12:1011-6. 
  28. Yilmaz A, Yildiz S, Kilic C, Can Z. Total phenolics, flavonoids, tannin contents and antioxidant properties of Pleurotus ostreatus cultivated on different wastes and sawdust. Int J Sec Metab 2017;4:1-9. 
  29. Gul R, Jan SU, Faridullah S, Sherani S, Jahan N. Preliminary phytochemical screening, quantitative analysis of alkaloids, and antioxidant activity of crude plant extracts from Ephedra intermedia indigenous to Balochistan. ScientificWorldJournal 2017;2017:5873648. 
  30. National Research Council. Guide for the care and use of laboratory animals. 6th ed. National Institutes of Health; 1985. p. 85-123. 
  31. Balsells M, Garcia-Patterson A, Sola I, Roque M, Gich I, Corcoy R. Glibenclamide, metformin, and insulin for the treatment of gestational diabetes: a systematic review and meta-analysis. BMJ 2015;350:h102. 
  32. Njogu SM, Arika WM, Machocho AK, Ngeranwa JJN, Njagi ENM. In vivo hypoglycemic effect of Kigelia africana (Lam): studies with alloxan-induced diabetic mice. J Evid Based Integr Med 2018;23:2515690X18768727. 
  33. Lenzen S. The mechanisms of alloxan- and streptozotocin-induced diabetes. Diabetologia 2008;51:216-26.  https://doi.org/10.1007/s00125-007-0886-7
  34. Singh R, Gholipourmalekabadi M, Shafikhani SH. Animal models for type 1 and type 2 diabetes: advantages and limitations. Front Endocrinol (Lausanne) 2024;15:1359685. 
  35. Rahman SS, Yasmin N, Rahman ATMM, Zaman A, Rahman MH, Rouf SMA. Evaluation and optimization of effective-dose of alloxan for inducing type-2 diabetes mellitus in Long Evans rat. Indian J Pharm Educ Res 2017;51(4 Suppl):S661-6.  https://doi.org/10.5530/ijper.51.4s.96
  36. Devaki K, Beulah U, Akila G, Narmadha R, Gopalakrishnan VK. Glucose lowering effect of aqueous extract of Bauhinia tomentosa L. on alloxan induced type 2 diabetes mellitus in wistar albino rats. J Basic Clin Pharm 2011;2:167-74. 
  37. Maroof K, Gan SH. Bee products and diabetes mellitus. In: Boyacioglu D, editor. Bee Products and Their Applications in the Food and Pharmaceutical Industries. Academic Press; 2022. p.63-114. 
  38. Fajarwati I, Solihin DD, Wresdiyati T, Batubara I. Self-recovery in diabetic Sprague Dawley rats induced by intraperitoneal alloxan and streptozotocin. Heliyon 2023;9:e15533. 
  39. Kottaisamy CPD, Raj DS, Prasanth Kumar V, Sankaran U. Experimental animal models for diabetes and its related complications-a review. Lab Anim Res 2021;37:23. 
  40. Ighodaro OM, Adeosun AM, Akinloye OA. Alloxan-induced diabetes, a common model for evaluating the glycemic-control potential of therapeutic compounds and plants extracts in experimental studies. Medicina (Kaunas) 2017;53:365-74.  https://doi.org/10.1016/j.medici.2018.02.001
  41. Sinha AK. Colorimetric assay of catalase. Anal Biochem 1972;47:389-94.  https://doi.org/10.1016/0003-2697(72)90132-7
  42. Fridovich I. Superoxide dismutases. An adaptation to a paramagnetic gas. J Biol Chem 1989;264:7761-4.  https://doi.org/10.1016/S0021-9258(18)83102-7
  43. Buege JA, Aust SD. Microsomal lipid peroxidation. Methods Enzymol 1978;52:302-10.  https://doi.org/10.1016/S0076-6879(78)52032-6
  44. Ubhenin AE, Adamude FA, Nweze CC, Dingwoke EJ. Protective effects of Pleurotus ostreatus in ameliorating carbon tetrachloride (ccl4) induced liver injury in Wistar rats. J Med Plants Res 2019;13:104-11.  https://doi.org/10.5897/JMPR2018.6714
  45. Skeggs LT Jr, Hochstrasser H. Multiple automatic sequential analysis. Clin Chem 1964;10:918-36.  https://doi.org/10.1093/clinchem/10.10.918
  46. Gran FC. A colorimetric method for the determination of calcium in blood serum. Acta Physiol Scand 1960;49:192-7.  https://doi.org/10.1111/j.1748-1716.1960.tb01943.x
  47. Tuominen VJ, Ruotoistenmaki S, Viitanen A, Jumppanen M, Isola J. ImmunoRatio: a publicly available web application for quantitative image analysis of estrogen receptor (ER), progesterone receptor (PR), and Ki-67. Breast Cancer Res 2010;12:R56. 
  48. World health statistics [Internet]. World Health Organization; 2014 Mar 31 [cited 2024 Mar 12]. Available from: https://www.who.int/docs/default-source/gho-documents/world-health-statistic-reports/world-health-statistics-2014.pdf. 
  49. Olokoba AB, Obateru OA, Olokoba LB. Type 2 diabetes mellitus: a review of current trends. Oman Med J 2012;27:269-73.  https://doi.org/10.5001/omj.2012.68
  50. Galaviz KI, Narayan KMV, Lobelo F, Weber MB. Lifestyle and the prevention of type 2 diabetes: a status report. Am J Lifestyle Med 2015;12:4-20. 
  51. Fazal F, Shahani HA, Gondal MF, Tanveer U, Haider M, Us Sabah N, Shahzad F, Ur Rehman ME. Attitudes and factors determining the practice of routine medical checkups in the people of Rawalpindi, Pakistan: a cross-sectional study. Cureus 2023;15:e38843. 
  52. Ojong IN, Nsemo AD, Aji P. Routine medical checkup knowledge, attitude and practice among health care workers in a tertiary health facility in Calabar, Cross River State, Nigeria. Glob J Health Sci 2020;12:27-37.  https://doi.org/10.5539/gjhs.v12n8p27
  53. Oshio T, Kan M. Educational level as a predictor of the incidences of non-communicable diseases among middle-aged Japanese: a hazards-model analysis. BMC Public Health 2019;19:852. 
  54. Adijat OA, Folakemi E, Adejumo A, Atolagbe JE. The prevalence and risk factors of diabetes mellitus among civil service workers in Osogbo, Osun State, Nigeria. J Hypertens Manag 2021;7:062. 
  55. Tella EE, Yunusa I, Hassan JH, Chindo IA, Oti VB. Prevalence, contributing factors and management strategies (self-management education) of type 2 diabetes patients in Nigeria: a review. Int J Diabetes Clin Res 2021;8:148. 
  56. Ibrahim MA, Habila JD, Koorbanally NA, Islam MS. Butanol fraction of Parkia biglobosa (Jacq.) G. Don leaves enhance pancreatic β-cell functions, stimulates insulin secretion and ameliorates other type 2 diabetes-associated complications in rats. J Ethnopharmacol 2016;183:103-11.  https://doi.org/10.1016/j.jep.2016.02.018
  57. Okon U, Owo D, Udokang N, Udobang J, Ekpenyong C. Oral administration of aqueous leaf extract of Ocimum gratissimum ameliorates polyphagia, polydipsia and weight loss in streptozotocin-induced diabetic rats. Am J Med Med Sci 2012;2:45-9.  https://doi.org/10.5923/j.ajmms.20120203.04
  58. Bindhu MR, Sathe V, Umadevi M. Synthesis, characterization and SERS activity of biosynthesized silver nanoparticles. Spectrochim Acta A Mol Biomol Spectrosc 2013;115:409-15.  https://doi.org/10.1016/j.saa.2013.06.047
  59. Dawang NS, AbdulHameed A, Ezra GA. Phytodiversity of three habitat types in Amurum forest: an important bird area in Jos, Nigeria. Afr J Nat Sci 2010;13:85-94. 
  60. Akunna GG, Saalu LC, Ogunlade B, Akingbade AM. Tackling infertility with medicinal plant: another instance. Glob J Med Plant Res 2013;1:93-105. 
  61. Chen RR, Liu ZK, Liu F, Ng TB. Antihyperglycaemic mechanisms of an aceteoside polymer from rose f lowers and a polysaccharide-protein complex from abalone mushroom. Nat Prod Res 2015;29:558-61.  https://doi.org/10.1080/14786419.2014.952230
  62. Erukainure OL, Okafor O, Ajayi A, Obode O, Ogunji A, Okporua T, Suberu Y, Oke O, Ozumba A, Oluwole O, Elemo G. Developed beverage from roselle calyx and selected fruits modulates β-cell function, improves insulin sensitivity, and attenuates hyperlipidaemia in diabetic rats. Beni-Suef Univ J Basic Appl Sci 2015;4:307-13. 
  63. Oboh H, Obahiagbon F, Osagie A, Omotosho A. Glycemic response of some local Nigerian drinks in healthy subjects. Niger J Nutr Sci 2011;32:79-84. 
  64. Clore JN, Stillman J, Sugerman H. Glucose-6-phosphatase flux in vitro is increased in type 2 diabetes. Diabetes 2000;49:969-74.  https://doi.org/10.2337/diabetes.49.6.969
  65. Guo X, Li H, Xu H, Woo S, Dong H, Lu F, Lange AJ, Wu C. Glycolysis in the control of blood glucose homeostasis. Acta Pharm Sin B 2012;2:358-67.  https://doi.org/10.1016/j.apsb.2012.06.002
  66. Islam MS, Choi H. Green tea, anti-diabetic or diabetogenic: a dose response study. Biofactors 2007;29:45-53.  https://doi.org/10.1002/biof.5520290105
  67. Esterbauer H, Schaur RJ, Zollner H. Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. Free Radic Biol Med 1991;11:81-128.  https://doi.org/10.1016/0891-5849(91)90192-6
  68. Kangralkar VA, Patil SD, Bandivadekar RM. Oxidative stress and diabetes: a review. Int J Pharm Appl 2010;1:38-45. 
  69. Landis GN, Tower J. Superoxide dismutase evolution and life span regulation. Mech Ageing Dev 2005;126:365-79.  https://doi.org/10.1016/j.mad.2004.08.012
  70. Chelikani P, Fita I, Loewen PC. Diversity of structures and properties among catalases. Cell Mol Life Sci 2004;61:192-208.  https://doi.org/10.1007/s00018-003-3206-5
  71. AlSaadi BH, AlHarbi SH, Ibrahim SRM, El-Kholy AA, El-Agamy DS, Mohamed GA. Hepatoprotective activity of costus speciosus (Koen ex. Retz.) against paracetamol-induced liver injury in mice. Afr J Tradit Complement Altern Med 2018;15:35-41. 
  72. Ezemagu UK, Akunna GG, Egwu OA, Uzomba GC, Nwite KN. Comparing Ficus vogelii leaf extract and Omeprazole as therapy and prophylaxis for aspirin-induced gastric ulcer in Wistar rat. Biomed Res 2019;30:697-703. 
  73. Hong X, Chi Z, Liu G, Huang H, Guo S, Fan J, Lin X, Qu L, Chen R, Wu L, Wang L, Zhang Q, Wu S, Pan Z, Lin H, Zhou Y, Zhang Y. Characteristics of renal function in patients diagnosed with COVID-19: an observational study. Front Med 2020;7:409. 
  74. Dere E, Polat F. The effect of paraquat on the activity of some enzymes in different tissues of mice (Mus musculus - Swiss albino). Turk J Biol 2001;25:323-32. 
  75. Vuksa M, Neskovic N, Vitorovic S, Karan V. Subacute toxicity of paraquat in rats--biochemical effects. Ecotoxicol Environ Saf 1983;7:475-83.  https://doi.org/10.1016/0147-6513(83)90087-8
  76. Attia AM, Nasr HM. Dimethoate-induced changes in biochemical parameters of experimental rat serum and its neutralization by black seed (Nigella sativa L.) oil. Slovak J Anim Sci 2009;42:87-94. 
  77. Samai M, Samai HH, Hague T, Naughton D, Chatterjee PK. Novel superoxide dismutase mimetics for protection against Paraquat-induced acute renal injury. Sierra Leone J Biomed Res 2010;2:54-64. 
  78. Akinloye OA, Adamson I, Ademuyiwa O, Arowolo TA. Supplementation of vitamins C, E and its combination on paraquatintoxicated rats: effects on some biochemical and markers of oxidative stress parameters. J Appl Pharm Sci 2011;1:85-91. 
  79. Smith GL, Shlipak MG, Havranek EP, Foody JM, Masoudi FA, Rathore SS, Krumholz HM. Serum urea nitrogen, creatinine, and estimators of renal function: mortality in older patients with cardiovascular disease. Arch Intern Med 2006;166:1134-42.  https://doi.org/10.1001/archinte.166.10.1134
  80. Karami S, Yanik EL, Moore LE, Pfeiffer RM, Copeland G, Gonsalves L, Hernandez BY, Lynch CF, Pawlish K, Engels EA. Risk of renal cell carcinoma among kidney transplant recipients in the United States. Am J Transplant 2016;16:3479-89.  https://doi.org/10.1111/ajt.13862
  81. Zhao S, Ghosh A, Lo CS, Chenier I, Scholey JW, Filep JG, Ingelfinger JR, Zhang SL, Chan JSD. Nrf2 deficiency upregulates intrarenal angiotensin-converting enzyme-2 and angiotensin 1-7 receptor expression and attenuates hypertension and nephropathy in diabetic mice. Endocrinology 2018;159:836-52.  https://doi.org/10.1210/en.2017-00752
  82. Heiss EH, Schachner D, Werner ER, Dirsch VM. Active NF-E2-related factor (Nrf2) contributes to keep endothelial NO synthase (eNOS) in the coupled state: role of reactive oxygen species (ROS), eNOS, and heme oxygenase (HO-1) levels. J Biol Chem 2009;284:31579-86.  https://doi.org/10.1074/jbc.M109.009175
  83. Aminzadeh MA, Nicholas SB, Norris KC, Vaziri ND. Role of impaired Nrf2 activation in the pathogenesis of oxidative stress and inflammation in chronic tubulo-interstitial nephropathy. Nephrol Dial Transplant 2013;28:2038-45.  https://doi.org/10.1093/ndt/gft022
  84. Fahey JW, Zalcmann AT, Talalay P. The chemical diversity and distribution of glucosinolates and isothiocyanates among plants. Phytochemistry 2001;56:5-51.  https://doi.org/10.1016/S0031-9422(00)00316-2
  85. Rushmore TH, Kong AN. Pharmacogenomics, regulation and signaling pathways of phase I and II drug metabolizing enzymes. Curr Drug Metab 2002;3:481-90. https://doi.org/10.2174/1389200023337171