Genomes and Genes
phase ii metabolic detoxication
Summary: The conjugation of exogenous substances with various hydrophilic substituents to form water soluble products that are excretable in URINE. Phase II modifications include GLUTATHIONE conjugation; ACYLATION; and AMINATION. Phase II enzymes include GLUTATHIONE TRANSFERASE and GLUCURONOSYLTRANSFERASE. In a sense these reactions detoxify phase I reaction products.
- Tlili S, Jebali J, Banni M, Haouas Z, Mlayah A, Helal A, et al. Multimarker approach analysis in common carp Cyprinus carpio sampled from three freshwater sites. Environ Monit Assess. 2010;168:285-98 pubmed publisher..Results showed a strong inhibition of cholinesterase activities in fish from Bir Mcherga and Sidi Saâd sites compared to Nebhana site. Relatively high level of MN is reported specially in fish blood from the Bir Mcherga site. ..
- Biasutto L, Marotta E, De Marchi U, Beltramello S, Bradaschia A, Garbisa S, et al. Heterogeneity and standardization of phase II metabolism in cultured cells. Cell Physiol Biochem. 2009;23:425-30 pubmed publisher..We suggest this metabolism-activating procedure be used to make studies with these cells more readily comparable. ..
- Lee S, Kang K, Lee H, Yun J, Jho E, Kim C, et al. The chemopreventive effects of Carpesium abrotanoides are mediated by induction of phase II detoxification enzymes and apoptosis in human colorectal cancer cells. J Med Food. 2010;13:39-46 pubmed publisher..abrotanoides can result from both the induction of phase II detoxification enzymes and from apoptosis. Thus, CAE could potentially be developed as a cancer chemopreventive agent for prevention or treatment of human cancers. ..
- Sheweita S, Hassan M, Bahashwan S. Schistosoma mansoni changes the activity of phase II drug-metabolizing enzymes: role of praziquantel as antibilharzial drug. Drug Metab Lett. 2010;4:134-8 pubmed..In addition, the present study could provide new evidence to the damage occurred in livers of S. mansoni-infected hosts. Also, it is suggested that praziquantel is the best drug of choice for schistosoma mansoni treatment. ..
- Antolino Lobo I, Meulenbelt J, Nijmeijer S, Scherpenisse P, van den Berg M, van Duursen M. Differential roles of phase I and phase II enzymes in 3,4-methylendioxymethamphetamine-induced cytotoxicity. Drug Metab Dispos. 2010;38:1105-12 pubmed publisher..Our data suggest that CYP2D6 as well as CYP3A4 play an important role in MDMA bioactivation. In addition, further studies are needed to address the differential roles of CYP3A4 and GSH/GST in MDMA bioactivation and detoxification. ..
- Horiuchi I, Kato Y, Nakamura A, Ishida K, Taguchi M, Hashimoto Y. Inhibitory and stimulative effects of amiodarone on metabolism of carvedilol in human liver microsomes. Biol Pharm Bull. 2010;33:717-20 pubmed..On the other hand, the stimulative effect of amiodarone and/or desethylamiodarone on the glucuronidation of R-carvedilol may compensate for the inhibitory effect of those on R-carvedilol oxidation. ..
- Chen M, LeDuc B, Kerr S, Howe D, Williams D. Identification of human UGT2B7 as the major isoform involved in the O-glucuronidation of chloramphenicol. Drug Metab Dispos. 2010;38:368-75 pubmed publisher..These results suggest that UGT2B7 is the primary human hepatic UDP-glucuronosyltransferase isoform catalyzing 3-O- and 1-O-CP glucuronidation with minor contributions from UGT1A6 and UGT1A9. ..
- Kamimura H, Nakada N, Suzuki K, Mera A, Souda K, Murakami Y, et al. Assessment of chimeric mice with humanized liver as a tool for predicting circulating human metabolites. Drug Metab Pharmacokinet. 2010;25:223-35 pubmed..Although requiring careful consideration of compound suitability, this model represents a potential tool for predicting human metabolites in combination with conventional in vitro systems. ..
- Johansson T, Weidolf L, Popp F, Tacke R, Jurva U. In vitro metabolism of haloperidol and sila-haloperidol: new metabolic pathways resulting from carbon/silicon exchange. Drug Metab Dispos. 2010;38:73-83 pubmed publisher..These studies showed the same differences in metabolic pathways as between sila-haloperidol and haloperidol. ..
- Cvilink V, Lamka J, Skalova L. Xenobiotic metabolizing enzymes and metabolism of anthelminthics in helminths. Drug Metab Rev. 2009;41:8-26 pubmed publisher..This induction can represent an advantageous defense strategy of the parasites and may facilitate the drug-resistance development. ..
- Kaeferstein H. Forensic relevance of glucuronidation in phase-II-metabolism of alcohols and drugs. Leg Med (Tokyo). 2009;11 Suppl 1:S22-6 pubmed publisher..For valid interpretation of complex cases in the future it may become necessary not only to quantify drugs and the phase-I-metabolites but also the phase-II-metabolites and discuss possible interactions in the metabolism. ..
- Hsu F, Lakshmi V, Zenser T. Characterization of new metabolites from in vivo biotransformation of 2-amino-3-methylimidazo[4,5-f]quinoline in mouse by mass spectrometry. J Mass Spectrom. 2009;44:1359-68 pubmed publisher..The observation of these more polar metabolites relative to IQ suggests that they may arise from a previously undescribed detoxification pathway. ..
- Natarajan V, Singh A, Kumar A, Sharma P, Kar H, Marrot L, et al. Transcriptional upregulation of Nrf2-dependent phase II detoxification genes in the involved epidermis of vitiligo vulgaris. J Invest Dermatol. 2010;130:2781-9 pubmed publisher..Our studies provide new insights into the role of phase II detoxification pathway in maintaining skin homeostasis and sustaining redox balance in vitiligo patients. ..
- Ohnuma T, Komatsu T, Nakayama S, Nishiyama T, Ogura K, Hiratsuka A. Induction of antioxidant and phase 2 drug-metabolizing enzymes by falcarindiol isolated from Notopterygium incisum extract, which activates the Nrf2/ARE pathway, leads to cytoprotection against oxidative and electrophilic stress. Arch Biochem Biophys. 2009;488:34-41 pubmed publisher..We found that falcarindiol was a novel inducer of AOEs and phase 2 DMEs and falcarindiol might exhibit chemopreventive activity. ..
- Cho I, Ki S, Brooks C, Kim S. Role of hepatitis B virus X repression of C/EBPbeta activity in the down-regulation of glutathione S-transferase A2 gene: implications in other phase II detoxifying enzyme expression. Xenobiotica. 2009;39:182-92 pubmed publisher..5. These results demonstrate that HBx inhibits the induction of phase II detoxifying enzymes, which is mediated by its interaction with C/EBPbeta, but not Nrf2, substantiating the specific role of HBx in phase II detoxifying capacity. ..
- Appeldoorn M, Vincken J, Gruppen H, Hollman P. Procyanidin dimers A1, A2, and B2 are absorbed without conjugation or methylation from the small intestine of rats. J Nutr. 2009;139:1469-73 pubmed publisher..Because PC contents of foods are relatively high, dimers may contribute to systemic effects of PC. ..
- Nishiyama T, Izawa T, Usami M, Ohnuma T, Ogura K, Hiratsuka A. Cooperation of NAD(P)H:quinone oxidoreductase 1 and UDP-glucuronosyltransferases reduces menadione cytotoxicity in HEK293 cells. Biochem Biophys Res Commun. 2010;394:459-63 pubmed publisher..These results demonstrated that NQO1 is not a detoxification enzyme for menadione and that UGT-mediated glucuronidation of menadiol is the most important detoxification process. ..
- Orlovius A, Guddat S, Parr M, Kohler M, Gutschow M, Thevis M, et al. Terbutaline sulfoconjugate: characterization and urinary excretion monitored by LC/ESI-MS/MS. Drug Test Anal. 2009;1:568-75 pubmed publisher..A glucuronidated, disulfated or trisulfated phase-II metabolite of terbutaline was not found. The measurement of phase-II metabolites is planned to be incorporated into existing screening procedures to allow a faster sample preparation. ..
- Zhu H, Jia Z, Zhou K, Misra H, Santo A, Gabrielson K, et al. Cruciferous dithiolethione-mediated coordinated induction of total cellular and mitochondrial antioxidants and phase 2 enzymes in human primary cardiomyocytes: cytoprotection against oxidative/electrophilic stress and doxorubicin toxicity. Exp Biol Med (Maywood). 2009;234:418-29 pubmed publisher
- Chang H, Ko M, Ishizuka M, Fujita S, Yabuki A, Hossain M, et al. Sodium 2-propenyl thiosulfate derived from garlic induces phase II detoxification enzymes in rat hepatoma H4IIE cells. Nutr Res. 2010;30:435-40 pubmed publisher..These results show that 2PTS can induce phase II enzymes, and its inductive effect is comparable or superior to that of diallyl trisulfide and tert-butylhydroquinone...
- Hecht S, Berg J, Hochalter J. Preferential glutathione conjugation of a reverse diol epoxide compared to a bay region diol epoxide of phenanthrene in human hepatocytes: relevance to molecular epidemiology studies of glutathione-s-transferase polymorphisms and cancer. Chem Res Toxicol. 2009;22:426-32 pubmed publisher
- Anandakumar P, Kamaraj S, Jagan S, Ramakrishnan G, Naveenkumar C, Asokkumar S, et al. Capsaicin alleviates the imbalance in xenobiotic metabolizing enzymes and tumor markers during experimental lung tumorigenesis. Mol Cell Biochem. 2009;331:135-43 pubmed publisher..Our present study unravels that CAP can effectively detoxify the carcinogens which discloses its anti-carcinogenic effect during experimental lung cancer. ..
- Philipp A, Wissenbach D, Zoerntlein S, Klein O, Kanogsunthornrat J, Maurer H. Studies on the metabolism of mitragynine, the main alkaloid of the herbal drug Kratom, in rat and human urine using liquid chromatography-linear ion trap mass spectrometry. J Mass Spectrom. 2009;44:1249-61 pubmed publisher..In rats, four metabolites were additionally conjugated to glucuronides and one to sulfate, but in humans, three metabolites to glucuronides and three to sulfates...
- Balliet R, Chen G, Dellinger R, Lazarus P. UDP-glucuronosyltransferase 1A10: activity against the tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol, and a potential role for a novel UGT1A10 promoter deletion polymorphism in cancer susceptibility. Drug Metab Dispos. 2010;38:484-90 pubmed publisher
- Perez J, Jayaprakasha G, Valdivia V, Munoz D, Dandekar D, AHMAD H, et al. Limonin methoxylation influences the induction of glutathione S-transferase and quinone reductase. J Agric Food Chem. 2009;57:5279-86 pubmed publisher..Our results indicated that modification of limonin has differential induction of phase II enzymes. These findings are indicative of a possible mechanism for the prevention of cancer by aiding in the detoxification of xenobiotics. ..
- Jana S, Mandlekar S. Role of phase II drug metabolizing enzymes in cancer chemoprevention. Curr Drug Metab. 2009;10:595-616 pubmed..Finally, we will provide a commentary on implementation of discovery and development programs for novel chemopreventive agents that are based on rational drug design, with lead optimization towards a safe and efficacious regimen in man. ..
- Chang S, Lee S, Bae W, Min K, Shin E, Oh G, et al. Heat stress activates interleukin-8 and the antioxidant system via Nrf2 pathways in human dental pulp cells. J Endod. 2009;35:1222-8 pubmed publisher..Collectively, these results show that heat-induced Nrf2 activation is the major regulatory pathway of cytoprotective gene expression against oxidative stress in HDP cells. ..
- Gan N, Mi L, Sun X, Dai G, Chung F, Song L. Sulforaphane protects Microcystin-LR-induced toxicity through activation of the Nrf2-mediated defensive response. Toxicol Appl Pharmacol. 2010;247:129-37 pubmed publisher..Results of our studies indicate that pretreatment of cells with 10muM SFN for 12h significantly protected cells from MC-LR-induced damage. SFN-induced protective response was mediated through Nrf2 pathway. ..
- Khiar N, Werner S, Mallouk S, Lieder F, Alcudia A, Fernandez I. Enantiopure sulforaphane analogues with various substituents at the sulfinyl sulfur: asymmetric synthesis and biological activities. J Org Chem. 2009;74:6002-9 pubmed publisher..The biological activity of these compounds as inductors of phase II detoxifying enzyme has been studied by determining their ability to activate the cytoprotective transcription factor Nrf2. ..
- . Genetic polymorphisms in phase I and phase II enzymes and breast cancer risk associated with menopausal hormone therapy in postmenopausal women. Breast Cancer Res Treat. 2010;119:463-74 pubmed publisher..Postmenopausal breast cancer risk associated with hormone therapy may be modified by genetically determined variations in phase I and II enzymes involved in steroid hormone metabolism. ..
- Levy S, Forman H. C-Myc is a Nrf2-interacting protein that negatively regulates phase II genes through their electrophile responsive elements. IUBMB Life. 2010;62:237-46 pubmed publisher..Finally, c-Myc decreased Nrf2 stability. Thus, our results suggest regulation of the EpRE/Nrf2 signaling pathway by c-Myc through both interaction with the EpRE binding complex and increased degradation of Nrf2. ..
- Sun H, Zeng Y, Pang K. Interplay of phase II enzymes and transporters in futile cycling: influence of multidrug resistance-associated protein 2-mediated excretion of estradiol 17beta-D-glucuronide and its 3-sulfate metabolite on net sulfation in perfused TR(-) and Wistar r. Drug Metab Dispos. 2010;38:769-80 pubmed publisher
- Azizi J, Ismail S, Mordi M, Ramanathan S, Said M, Mansor S. In vitro and in vivo effects of three different Mitragyna speciosa korth leaf extracts on phase II drug metabolizing enzymes--glutathione transferases (GSTs). Molecules. 2010;15:432-41 pubmed publisher..An increase in GST specific activity was generally observed. However, only Mitragyna speciosa aqueous extract with a dosage of 100 mg/kg showed significant results: 129% compared to control...
- Kalthoff S, Ehmer U, Freiberg N, Manns M, Strassburg C. Interaction between oxidative stress sensor Nrf2 and xenobiotic-activated aryl hydrocarbon receptor in the regulation of the human phase II detoxifying UDP-glucuronosyltransferase 1A10. J Biol Chem. 2010;285:5993-6002 pubmed publisher..Cellular protection by glucuronidation is thus inducible by xenobiotics via AhR and by oxidative metabolites via Nrf2 linking glucuronidation to cellular protection and defense against oxidative stress. ..
- Manoharan S, Panjamurthy K, Menon V, Balakrishnan S, Alias L. Protective effect of Withaferin-A on tumour formation in 7,12-dimethylbenz[a]anthracene induced oral carcinogenesis in hamsters. Indian J Exp Biol. 2009;47:16-23 pubmed
- Thompson E, Burwinkel K, Chava A, Notch E, Mayer G. Activity of Phase I and Phase II enzymes of the benzo[a]pyrene transformation pathway in zebrafish (Danio rerio) following waterborne exposure to arsenite. Comp Biochem Physiol C Toxicol Pharmacol. 2010;152:371-8 pubmed publisher..This evidence suggests that As(III) has the potential to modify components of the B[a]P biotransformation pathway in vivo via a disruption of CYP1A activity by way of both pre- and post-translational mechanisms. ..
- Lee S, Kim C, Lee H, Yun J, Nho C. Induction of the phase II detoxification enzyme NQO1 in hepatocarcinoma cells by lignans from the fruit of Schisandra chinensis through nuclear accumulation of Nrf2. Planta Med. 2009;75:1314-8 pubmed publisher..The results of the current study suggest that TGH functions as a novel monofunctional inducer that specifically upregulates phase II enzymes through the Nrf2-ARE pathway. TGH thus represents a potential liver cancer prevention agent. ..
- Rodrigues Lima F, Dairou J, Busi F, Dupret J. Human arylamine N-acetyltransferase 1: a drug-metabolizing enzyme and a drug target?. Curr Drug Targets. 2010;11:759-66 pubmed..Recent published data suggest that NAT1 could be of therapeutic interest for cancer. We provide here an overview on the putative involvement of NAT1 in cancer and its possible role as a drug target. ..
- Gerhauser C, Klimo K, Hümmer W, Hölzer J, Petermann A, Garreta Rufas A, et al. Identification of 3-hydroxy-beta-damascone and related carotenoid-derived aroma compounds as novel potent inducers of Nrf2-mediated phase 2 response with concomitant anti-inflammatory activity. Mol Nutr Food Res. 2009;53:1237-44 pubmed publisher
- Jancova P, Anzenbacher P, Anzenbacherova E. Phase II drug metabolizing enzymes. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2010;154:103-16 pubmed..Reduced metabolising capacity of Phase II enzymes can lead to toxic effects of clinically used drugs. Gene polymorphism/ lack of these enzymes may often play a role in several forms of cancer. ..
- Zhang X, Zhao X, Ma Z. PYDDT, a novel phase 2 enzymes inducer, activates Keap1-Nrf2 pathway via depleting the cellular level of glutathione. Toxicol Lett. 2010;199:93-101 pubmed publisher..We concluded from our findings that conjugation with intracellular GSH by PYDDT might lead to Keap1 S-glutathionylation and was a key event involved in its Nrf2 inducing activity. ..