Generic placeholder image

Current Drug Metabolism


ISSN (Print): 1389-2002
ISSN (Online): 1875-5453

General Research Article

Profiles of Two Glycaemia Modifying Drugs on the Expression of Rat and Human Sulfotransferases

Author(s): Sangita M. Dutta*, Guangping Chen and Smarajit Maiti

Volume 22 , Issue 3 , 2021

Published on: 30 November, 2020

Page: [240 - 248] Pages: 9

DOI: 10.2174/1389200221666201130123837

Price: $65


Aims: To study the effects of blood glucose regulating compounds on human and rat sulfotransferases (SULTs) expressions.

Background: Phase-II enzymes, sulfotransferases catalyze the sulfuryl-group-transfer to endogenous/exogenous compounds. The alteration of expressions of SULTs may have influence on the sulfation of its substrate and other biomolecules.

Objectives: The influence of the altered biotransformation might alter different biochemical events, drug-drug interactions and bioaccumulation or excretion pattern of certain drug.

Methods: In this brief study, diabetes-inducing drug streptozotocin (STZ; 10 or 50 mg/kg to male Sprague Dawley rat for 2 weeks) or hyperglycemia controlling drug tolbutamide (TLB 0.1 or 10μM to human hepato-carcinoma cells, HepG2 for 10 days) was applied and the SULTs expressions were verified. Extensive protein-protein (STa, SULT2A1/DHEAST) interactions were studied by the STRING (Search-Tool-for-the-Retrieval-of-Interacting Genes/Proteins) Bioinformatics-software.

Results: Present result suggests that while STZ increased the STa (in rat) (dehydroepiandrosterone catalyzing SULT; DHEAST in human HepG2), tolbutamide decreased PPST (phenol catalyzing SULT) and DHEAST activity in human HepG2 cells. Moderate decreases of MPST (monoamine catalyzing SULT) and EST (estrogen catalyzing) activities are noticed in this case. STa/DHEAST was found to be highly interactive to SHBG/- sex-hormone-binding-globulin; PPARα/lipid-metabolism-regulator; FABP1/fatty-acid-binding-protein.

Conclusion: Streptozotocin and tolbutamide, these two glycaemia-modifying drugs demonstrated regulation of rat and human SULTs activities. The reciprocal nature of these two drugs on SULTs expression may be associated with their contrasting abilities in influencing glucose-homeostasis. Possible association of certain SULT-isoform with hepatic fat-regulations may indicate an unfocused link between calorie-metabolism and the glycemic-state of an individual. Explorations of this work may uncover the role of sulfation metabolism of specific biomolecule on cellular glycemic regulation.

Keywords: Diabetes, streptozotocin, tolbutamide, sulfotransferase, rat liver, HepG2.

Graphical Abstract
Chapman, E.; Best, M.D.; Hanson, S.R.; Wong, C.H. Sulfotransferases: structure, mechanism, biological activity, inhibition, and synthetic utility. Angew. Chem. Int. Ed. Engl., 2004, 43(27), 3526-3548.
[] [PMID: 15293241]
Crettol, S.; Petrovic, N.; Murray, M. Pharmacogenetics of phase I and phase II drug metabolism. Curr. Pharm. Des., 2010, 16(2), 204-219.
[] [PMID: 19835560]
Hoda, M.; Hemaiswarya, S.; Doble, M. Pharmacokinetics and Pharmacodynamics of Polyphenols.Role of Phenolic Phytochemicals in Diabetes Management; Springer: Singapore, 2019, pp. 159-173.
Potter, B.V.L. SULFATION PATHWAYS: Steroid sulphatase inhibition via aryl sulphamates: clinical progress, mechanism and future prospects. J. Mol. Endocrinol., 2018, 61(2), T233-T252.
[] [PMID: 29618488]
Mendis, E.; Kim, M.M.; Rajapakse, N.; Kim, S.K. Sulfated glucosamine inhibits oxidation of biomolecules in cells via a mechanism involving intracellular free radical scavenging. Eur. J. Pharmacol., 2008, 579(1-3), 74-85.
[] [PMID: 18036590]
Barbosa, A.C.S.; Feng, Y.; Yu, C.; Huang, M.; Xie, W. Estrogen sulfotransferase in the metabolism of estrogenic drugs and in the pathogenesis of diseases. Expert Opin. Drug Metab. Toxicol., 2019, 15(4), 329-339.
[] [PMID: 30822161]
Foster, P.A.; Mueller, J.W. SULFATION PATHWAYS: Insights into steroid sulfation and desulfation pathways. J. Mol. Endocrinol., 2018, 61(2), T271-T283.
[] [PMID: 29764919]
Luo, L.; Zhou, C.; Hui, Y.; Kurogi, K.; Sakakibara, Y.; Suiko, M.; Liu, M.C. Human cytosolic sulfotransferase SULT1C4 mediates the sulfation of doxorubicin and epirubicin. Drug Metab. Pharmacokinet., 2016, 31(2), 163-166.
[] [PMID: 26948952]
Renskers, K.J.; Feor, K.D.; Roth, J.A. Sulfation of dopamine and other biogenic amines by human brain phenol sulfotransferase. J. Neurochem., 1980, 34(6), 1362-1368.
[] [PMID: 6929898]
Alnouti, Y. Bile Acid sulfation: a pathway of bile acid elimination and detoxification. Toxicol. Sci., 2009, 108(2), 225-246.
[] [PMID: 19131563]
Maiti, S.; Chen, G. Methotrexate is a novel inducer of rat liver and intestinal sulfotransferases. Arch. Biochem. Biophys., 2003, 418(2), 161-168.
[] [PMID: 14522587]
Maiti, S.; Chen, G. Ethanol up-regulates phenol sulfotransferase (SULT1A1) and hydroxysteroid sulfotransferase (SULT2A1) in rat liver and intestine. Arch. Physiol. Biochem., 2015, 121(2), 68-74.
[] [PMID: 25720860]
Maiti, S.; Chen, X.; Chen, G. All-trans retinoic acid induction of sulfotransferases. Basic Clin. Pharmacol. Toxicol., 2005, 96(1), 44-53.
[] [PMID: 15667595]
Jana, P.; Khan, M.M.; De, S.K.; Sinha, A.K.; Guha, S.; Khan, G.A.; Maiti, S. Estriol inhibits dermcidin isoform-2 induced inflammatory cytokine expression via nitric oxide synthesis in human neutrophil. Curr. Mol. Med., 2018, 18(10), 672-678.
[] [PMID: 30734678]
Zhai, T.; Wang, J.; Sun, L.; Chen, Y. The effect of streptozotocin and alloxan on the mRNA expression of rat hepatic transporters in vivo . AAPS PharmSciTech, 2015, 16(4), 767-770.
[] [PMID: 25549789]
Alimohammadi, S.; Hobbenaghi, R.; Javanbakht, J.; Kheradmand, D.; Mortezaee, R.; Tavakoli, M.; Khadivar, F.; Akbari, H. Protective and antidiabetic effects of extract from Nigella sativa on blood glucose concentrations against streptozotocin (STZ)-induced diabetic in rats: an experimental study with histopathological evaluation. Diagn. Pathol., 2013, 8, 137.
[] [PMID: 23947821]
Jensen, L.J.; Kuhn, M.; Stark, M.; Chaffron, S.; Creevey, C.; Muller, J.; Doerks, T.; Julien, P.; Roth, A.; Simonovic, M.; Bork, P.; von Mering, C.; Roth, A. STRING 8--a global view on proteins and their functional interactions in 630 organisms. Nucleic Acids Res., 2009, 37(Database issue), D412-D416.
[] [PMID: 18940858]
Taboada, B.; Verde, C.; Merino, E. High accuracy operon prediction method based on STRING database scores. Nucleic Acids Res., 2010, 38(12), e130.
[] [PMID: 20385580]
von Mering, C.; Jensen, L.J.; Snel, B.; Hooper, S.D.; Krupp, M.; Foglierini, M.; Jouffre, N.; Huynen, M.A.; Bork, P. STRING: known and predicted protein-protein associations, integrated and transferred across organisms. Nucleic Acids Res., 2005, 33(Database issue)(Suppl. 1), D433-D437.
[] [PMID: 15608232]
Atlas, D. International diabetes federation. IDF Diabetes Atlas, 7th ed; International Diabetes Federation: Brussels, Belgium, 2015.
Chen, F.; Li, D.Y.; Zhang, B.; Sun, J.Y.; Sun, F.; Ji, X.; Qiu, J.C.; Parker, R.B.; Laizure, S.C.; Xu, J. Alterations of drug-metabolizing enzymes and transporters under diabetic conditions: what is the potential clinical significance? Drug Metab. Rev., 2018, 50(3), 369-397.
[] [PMID: 30221555]
Larson, E.C.; Pond, C.D.; Rai, P.P.; Matainaho, T.K.; Piskaut, P.; Franklin, M.R.; Barrows, L.R. Traditional preparations and methanol extracts of medicinal plants from Papua New Guinea exhibit similar cytochrome p450 inhibition. Evid. Based Complement. Alternat. Med., 2016, 2016, 7869710.
[] [PMID: 27642356]
Gomes, A.I.P.V. In vitro assessment of cytochrome P450 2C9 inhibition: tolbutamide as probe substrate and HepaRG cells as human hepatic model. Doctoral dissertation. Universidade Da Beira Interior, Portugal. 2016.
Easterbrook, J.; Lu, C.; Sakai, Y.; Li, A.P. Effects of organic solvents on the activities of cytochrome P450 isoforms, UDP-dependent glucuronyl transferase, and phenol sulfotransferase in human hepatocytes. Drug Metab. Dispos., 2001, 29(2), 141-144.
[PMID: 11159803]
Bai, Q.; Zhang, X.; Xu, L.; Kakiyama, G.; Heuman, D.; Sanyal, A.; Pandak, W.M.; Yin, L.; Xie, W.; Ren, S. Oxysterol sulfation by cytosolic sulfotransferase suppresses liver X receptor/sterol regulatory element binding protein-1c signaling pathway and reduces serum and hepatic lipids in mouse models of nonalcoholic fatty liver disease. Metabolism, 2012, 61(6), 836-845.
[] [PMID: 22225954]
Fan, L.Q.; You, L.; Brown-Borg, H.; Brown, S.; Edwards, R.J.; Corton, J.C. Regulation of phase I and phase II steroid metabolism enzymes by PPAR alpha activators. Toxicology, 2004, 204(2-3), 109-121.
[] [PMID: 15388238]
Li, Y.; Xu, Y.; Li, X.; Qin, Y.; Hu, R. Effects of PPAR-α agonist and IGF-1 on estrogen sulfotransferase in human vascular endothelial and smooth muscle cells. Mol. Med. Rep., 2013, 8(1), 133-139.
[] [PMID: 23685729]
Gupte, A.A.; Pownall, H.J.; Hamilton, D.J. Estrogen: an emerging regulator of insulin action and mitochondrial function. J. Diabetes Res., 2015, 2015, 916585.
[] [PMID: 25883987]
Sharer, J.E.; Shipley, L.A.; Vandenbranden, M.R.; Binkley, S.N.; Wrighton, S.A. Comparisons of phase I and phase II in vitro hepatic enzyme activities of human, dog, rhesus monkey, and cynomolgus monkey. Drug Metab. Dispos., 1995, 23(11), 1231-1241.
[PMID: 8591724]
Prueksaritanont, T.; Gorham, L.M.; Hochman, J.H.; Tran, L.O.; Vyas, K.P. Comparative studies of drug-metabolizing enzymes in dog, monkey, and human small intestines, and in Caco-2 cells. Drug Metab. Dispos., 1996, 24(6), 634-642.
[PMID: 8781778]
Kirkpatrick, R.B.; Kraft, B.G. Effect of streptozotocin-induced diabetes on bile acid sulfation in male rat liver. Am. J. Physiol., 1984, 247(3 Pt 1), G226-G230.
[] [PMID: 6591805]
Lv, L.; Wu, S.Y.; Wang, G.F.; Zhang, J.J.; Pang, J.X.; Liu, Z.Q.; Xu, W.; Wu, S.G.; Rao, J.J. Effect of astragaloside IV on hepatic glucose-regulating enzymes in diabetic mice induced by a high-fat diet and streptozotocin. Phytother. Res., 2010, 24(2), 219-224.
[] [PMID: 19610026]
Unger, E.; Pettersson, I.; Eriksson, U.J.; Lindahl, U.; Kjellén, L. Decreased activity of the heparan sulfate-modifying enzyme glucosaminyl N-deacetylase in hepatocytes from streptozotocin-diabetic rats. J. Biol. Chem., 1991, 266(14), 8671-8674.
[] [PMID: 2026583]
Almási, A.; Pinto, É.D.I.L.N.; Kovács, N.P.; Fischer, T.; Markovics, Z.; Fischer, E.; Perjési, P. Changes in hepatic metabolic enzyme activities and biliary excretion of 4-nitrophenol in streptozotocin induced diabetic rats. Braz. J. Pharm. Sci., 2018, 54(1)
Komatsu, K.; Ito, K.; Nakajima, Y.; Kanamitsu, Si.; Imaoka, S.; Funae, Y.; Green, C.E.; Tyson, C.A.; Shimada, N.; Sugiyama, Y. Prediction of in vivo drug-drug interactions between tolbutamide and various sulfonamides in humans based on in vitro experiments. Drug Metab. Dispos., 2000, 28(4), 475-481.
[PMID: 10725317]
Bhattacharya, S.; Ghosh, R.; Maiti, S.; Khan, G.A.; Sinha, A.K. The activation by glucose of liver membrane nitric oxide synthase in the synthesis and translocation of glucose transporter-4 in the production of insulin in the mice hepatocytes. PLoS One, 2013, 8(12), e81935.
[] [PMID: 24349154]
Jana, P.; Maiti, S.; Ghosh, R.; Ghosh, T.K.; Sinha, A.K. Estriol, a stimulator of nitric oxide synthesis in platelets, and its role as the powerful inhibitor of platelet aggregation. Cardiovasc. Endocrinol. Metab., 2013, 2(3), 50-54.
Riazi, S.; Maric, C.; Ecelbarger, C.A. 17-beta Estradiol attenuates streptozotocin-induced diabetes and regulates the expression of renal sodium transporters. Kidney Int., 2006, 69(3), 471-480.
[] [PMID: 16514430]
Fukui, M.; Kitagawa, Y.; Kamiuchi, K.; Hasegawa, G.; Yoshikawa, T.; Nakamura, N. Association between serum estradiol concentrations and carotid atherosclerosis in men with type 2 diabetes mellitus. Metabolism, 2008, 57(2), 285-289.
[] [PMID: 18191062]
Li, Y.; Huang, J.; Yan, Y.; Liang, J.; Liang, Q.; Lu, Y.; Zhao, L.; Li, H. Preventative effects of resveratrol and estradiol on streptozotocin-induced diabetes in ovariectomized mice and the related mechanisms. PLoS One, 2018, 13(10), e0204499.
[] [PMID: 30273360]
Xu, Y.; Yang, X.; Wang, Z.; Li, M.; Ning, Y.; Chen, S.; Yin, L.; Li, X. Estrogen sulfotransferase (SULT1E1) regulates inflammatory response and lipid metabolism of human endothelial cells via PPARγ. Mol. Cell. Endocrinol., 2013, 369(1-2), 140-149.
[] [PMID: 23384540]
Yalcin, E.B.; Kulkarni, S.R.; Slitt, A.L.; King, R. Bisphenol A sulfonation is impaired in metabolic and liver disease. Toxicol. Appl. Pharmacol., 2016, 292, 75-84.
[] [PMID: 26712468]
Garbacz, W.G.; Jiang, M.; Xie, W. Sex-dependent role of estrogen sulfotransferase and steroid sulfatase in metabolic homeostasis. Adv. Exp. Med. Biol., 2017, 1043, 455-469.
[] [PMID: 29224107]
Li, J.; Wei, J.; Xu, P.; Yan, M.; Li, J.; Chen, Z.; Jin, T. Impact of diabetes-related gene polymorphisms on the clinical characteristics of type 2 diabetes Chinese Han population. Oncotarget, 2016, 7(51), 85464-85471.
[] [PMID: 27863428]
Zhou, X.; Rougée, L.R.; Bedwell, D.W.; Cramer, J.W.; Mohutsky, M.A.; Calvert, N.A.; Moulton, R.D.; Cassidy, K.C.; Yumibe, N.P.; Adams, L.A.; Ruterbories, K.J. Difference in the pharmacokinetics and hepatic metabolism of antidiabetic drugs in zucker diabetic fatty and sprague-dawley rats. Drug Metab. Dispos., 2016, 44(8), 1184-1192.
[] [PMID: 27217490]
Runge-Morris, M.; Vento, C. Effects of streptozotocin-induced diabetes on rat liver sulfotransferase gene expression. Drug Metab. Dispos., 1995, 23(4), 455-459.
[PMID: 7600911]
Wang, X.; Wang, F.; Zhang, Y.; Xiong, H.; Zhang, Y.; Zhuang, P.; Zhang, Y. Diabetic cognitive dysfunction is associated with increased bile acids in liver and activation of bile acid signaling in intestine. Toxicol. Lett., 2018, 287, 10-22.
[] [PMID: 29382564]
Meng, X.M.; Ma, X.X.; Tian, Y.L.; Jiang, Q.; Wang, L.L.; Shi, R.; Ding, L.; Pang, S.G. Metformin improves the glucose and lipid metabolism via influencing the level of serum total bile acids in rats with streptozotocin-induced type 2 diabetes mellitus. Eur. Rev. Med. Pharmacol. Sci., 2017, 21(9), 2232-2237.
[PMID: 28537659]
Chen, Z.; Hu, H.; Chen, M.; Luo, X.; Yao, W.; Liang, Q.; Yang, F.; Wang, X. Association of Triglyceride to high-density lipoprotein cholesterol ratio and incident of diabetes mellitus: a secondary retrospective analysis based on a Chinese cohort study. Lipids Health Dis., 2020, 19(1), 33.
[] [PMID: 32131838]
Bi, Y.; Wang, Y.; Xie, W. The interplay between hepatocyte nuclear factor 4α (HNF4α) and cholesterol sulfotransferase (SULT2B1b) in hepatic energy homeostasis. Liver Research, 2019, 3(3-4), 143-149.
Garbacz, W.G.; Jiang, M.; Xu, M.; Yamauchi, J.; Dong, H.H.; Xie, W. Sex- and tissue-specific role of estrogen sulfotransferase in energy homeostasis and insulin sensitivity. Endocrinology, 2017, 158(11), 4093-4104.
[] [PMID: 28938414]
Dong, B.; Saha, P.K.; Huang, W.; Chen, W.; Abu-Elheiga, L.A.; Wakil, S.J.; Stevens, R.D.; Ilkayeva, O.; Newgard, C.B.; Chan, L.; Moore, D.D. Activation of nuclear receptor CAR ameliorates diabetes and fatty liver disease. Proc. Natl. Acad. Sci. USA, 2009, 106(44), 18831-18836.
[] [PMID: 19850873]
Chen, X.; Maiti, S.; Zhang, J.; Chen, G. Nuclear receptor interactions in methotrexate induction of human dehydroepiandrosterone sulfotransferase (hSULT2A1). J. Biochem. Mol. Toxicol., 2006, 20(6), 309-317.
[] [PMID: 17163485]
Chen, X.; Zhang, J.; Baker, S.M.; Chen, G. Human constitutive androstane receptor mediated methotrexate induction of human dehydroepiandrosterone sulfotransferase (hSULT2A1). Toxicology, 2007, 231(2-3), 224-233.
[] [PMID: 17276571]
Yao, Y.; Zhao, X.; Xin, J.; Wu, Y.; Li, H. Coumarins improved type 2 diabetes induced by high-fat diet and streptozotocin in mice via antioxidation. Can. J. Physiol. Pharmacol., 2018, 96(8), 765-771.
[] [PMID: 29641229]
Case, R.M. Is the rat pancreas an appropriate model of the human pancreas? Pancreatology, 2006, 6(3), 180-190.
[] [PMID: 16534243]
Dolenšek, J.; Rupnik, M.S.; Stožer, A. Structural similarities and differences between the human and the mouse pancreas. Islets, 2015, 7(1), e1024405.
[] [PMID: 26030186]
MacDonald, M.J.; Longacre, M.J.; Stoker, S.W.; Kendrick, M.; Thonpho, A.; Brown, L.J.; Hasan, N.M.; Jitrapakdee, S.; Fukao, T.; Hanson, M.S.; Fernandez, L.A.; Odorico, J. Differences between human and rodent pancreatic islets: low pyruvate carboxylase, atp citrate lyase, and pyruvate carboxylation and high glucose-stimulated acetoacetate in human pancreatic islets. J. Biol. Chem., 2011, 286(21), 18383-18396.
[] [PMID: 21454710]

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy