{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,5]],"date-time":"2026-04-05T10:20:26Z","timestamp":1775384426404,"version":"3.50.1"},"reference-count":43,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2015,12,29]],"date-time":"2015-12-29T00:00:00Z","timestamp":1451347200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Sciences Foundation of China","award":["81202581"],"award-info":[{"award-number":["81202581"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>This study was aimed to investigate whether vitamin A deficiency could alter P-GP expression and function in tissues of rats and whether such effects affected the drug distribution in vivo of vitamin A-deficient rats. We induced vitamin A-deficient rats by giving them a vitamin A-free diet for 12 weeks. Then, Abcb1\/P-GP expression was evaluated by qRT-PCR and Western blot. qRT-PCR analysis revealed that Abcb1a mRNA levels were increased in hippocampus and liver. In kidney, it only showed an upward trend. Abcb1b mRNA levels were increased in hippocampus, but decreased in cerebral cortex, liver and kidney. Western blot results were in good accordance with the alterations of Abcb1b mRNA levels. P-GP function was investigated through tissue distribution and body fluid excretion of rhodamine 123 (Rho123), and the results proclaimed that P-GP activities were also in good accordance with P-GP expression in cerebral cortex, liver and kidney. The change of drug distribution was also investigated through the tissue distribution of vincristine, and the results showed a significantly upward trend in all indicated tissues of vitamin A-deficient rats. In conclusion, vitamin A deficiency may alter Abcb1\/P-GP expression and function in rat tissues, and the alterations may increase drug activity\/toxicity through the increase of tissue accumulation.<\/jats:p>","DOI":"10.3390\/molecules21010046","type":"journal-article","created":{"date-parts":[[2015,12,29]],"date-time":"2015-12-29T10:00:08Z","timestamp":1451383208000},"page":"46","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The Alterations in the Expression and Function of P-Glycoprotein in Vitamin A-Deficient Rats as well as the Effect of Drug Disposition in Vivo"],"prefix":"10.3390","volume":"21","author":[{"given":"Yubang","family":"Wang","sequence":"first","affiliation":[{"name":"The Key Laboratory of Modern Toxicology of Ministry of Education, Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, China"},{"name":"The Center for Hygienic Analysis and Detection, Nanjing Medical University, Nanjing 211166, Jiangsu, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heng","family":"Qin","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Modern Toxicology of Ministry of Education, Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, China"},{"name":"The Center for Hygienic Analysis and Detection, Nanjing Medical University, Nanjing 211166, Jiangsu, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chengxiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Modern Toxicology of Ministry of Education, Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, China"},{"name":"The Center for Hygienic Analysis and Detection, Nanjing Medical University, Nanjing 211166, Jiangsu, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fei","family":"Huan","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Modern Toxicology of Ministry of Education, Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, China"},{"name":"The Center for Hygienic Analysis and Detection, Nanjing Medical University, Nanjing 211166, Jiangsu, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ting","family":"Yan","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Modern Toxicology of Ministry of Education, Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, China"},{"name":"The Center for Hygienic Analysis and Detection, Nanjing Medical University, Nanjing 211166, Jiangsu, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lulu","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Modern Toxicology of Ministry of Education, Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, China"},{"name":"The Center for Hygienic Analysis and Detection, Nanjing Medical University, Nanjing 211166, Jiangsu, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2015,12,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0278-6915(00)00110-1","article-title":"The effect of retinol on hepatic and renal drug-metabolising enzymes","volume":"39","author":"Bray","year":"2001","journal-title":"Food Chem. Toxicol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.bcp.2009.08.012","article-title":"Retinoids activate RXR\/CAR-mediated pathway and induce CYP3A","volume":"79","author":"Chen","year":"2010","journal-title":"Biochem. Pharmacol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2204","DOI":"10.1016\/j.bcp.2008.02.030","article-title":"Retinoids induce cytochrome P450 3A4 through RXR\/VDR-mediated pathway","volume":"75","author":"Wang","year":"2008","journal-title":"Biochem. Pharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0169-409X(02)00169-2","article-title":"Mammalian drug efflux transporters of the ATP binding cassette (ABC) family: An overview","volume":"55","author":"Schinkel","year":"2003","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1634\/theoncologist.12-8-927","article-title":"Concise review: Clinical relevance of drug drug and herb drug interactions mediated by the ABC transporter ABCB1 (MDR1, P-glycoprotein)","volume":"12","author":"Marchetti","year":"2007","journal-title":"Oncologist"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.1124\/dmd.105.004770","article-title":"Modulation of P-glycoprotein expression in hyperthyroid rat tissues","volume":"33","author":"Nishio","year":"2005","journal-title":"Drug Metab. Dispos."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1124\/dmd.30.7.838","article-title":"Tissue distribution and chemical induction of multiple drug resistance genes in rats","volume":"30","author":"Brady","year":"2002","journal-title":"Drug Metab. Dispos."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2909","DOI":"10.1167\/iovs.02-1142","article-title":"Molecular evidence and functional expression of P-glycoprotein (MDR1) in human and rabbit cornea and corneal epithelial cell lines","volume":"44","author":"Dey","year":"2003","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/j.tips.2004.06.002","article-title":"Importance of P-glycoprotein at blood\u2013tissue barriers","volume":"25","author":"Fromm","year":"2004","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1970","DOI":"10.1124\/dmd.107.015107","article-title":"Efflux transporter expression and acetaminophen metabolite excretion are altered in rodent models of nonalcoholic fatty liver disease","volume":"35","author":"Lickeig","year":"2007","journal-title":"Drug Metab. Dispos."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1124\/jpet.106.112631","article-title":"Down-regulation of intestinal drug transporters in chronic renal failure in rats","volume":"320","author":"Naud","year":"2007","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_12","first-page":"4618","article-title":"MDR1 gene overexpression and altered degree of methylation at the promoter region in bladder cancer during chemotherapeutic treatment","volume":"6","author":"Tada","year":"2000","journal-title":"Clin. Cancer Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1038\/aps.2011.33","article-title":"Tissue-specific alterations in expression and function of P-glycoprotein in streptozotocin-induced diabetic rats","volume":"32","author":"Zhang","year":"2011","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1124\/pr.55.4.2","article-title":"Induction of drug metabolism: The role of nuclear receptors","volume":"55","author":"Handschin","year":"2003","journal-title":"Pharmacol. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1016\/j.bcp.2012.01.030","article-title":"Nuclear receptors in the multidrug resistance through the regulation of drug-metabolizing enzymes and drug transporters","volume":"83","author":"Chen","year":"2012","journal-title":"Biochem. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"453","DOI":"10.3390\/jcm3020453","article-title":"The Roles of Vitamin A in the Regulation of Carbohydrate, Lipid, and Protein Metabolism","volume":"3","author":"Chen","year":"2014","journal-title":"J. Clin. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.livsci.2010.09.023","article-title":"Low levels of dietary vitamin A increase intramuscular fat content and polyunsaturated fatty acid proportion in liver from lean pigs","volume":"137","author":"Olivares","year":"2011","journal-title":"Livest. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"147","DOI":"10.3177\/jnsv.61.147","article-title":"Vitamin A deficiency inpairs induction of oral tolerance in mice","volume":"61","author":"Nakamoto","year":"2015","journal-title":"J. Nutr. Sci. Vitaminol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/S0006-291X(02)00478-3","article-title":"Validation of a quantitative method for real time PCR kinetics","volume":"294","author":"Liu","year":"2002","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1111\/j.1476-5381.2009.00634.x","article-title":"Combined effects of epileptic seizure and phenobarbital induced overexpression of P-glycoprotein in brain of chemically kindled rats","volume":"159","author":"Jing","year":"2010","journal-title":"Br. J. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1055\/s-0029-1240815","article-title":"Increased plasma exposures of five protoberberine alkaloids from Coptidis Rhizoma in streptozotocin-induced diabetic rats: Is P-GP involved?","volume":"76","author":"Yu","year":"2010","journal-title":"Planta Med."},{"key":"ref_22","first-page":"786","article-title":"Simultaneous quantitative determination of five alkaloids in Catharanthus roseus by HPLC-ESI-MS\/MS","volume":"12","author":"Zhang","year":"2014","journal-title":"Chin. J. Nat. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/S1570-0232(04)00508-2","article-title":"Determination of vincristine in mouse plasma and brain tissues by liquid chromatography-electrospray mass spectrometry","volume":"809","author":"Guo","year":"2004","journal-title":"J. Chromatogr. B Anal. Technol. Biomed. Life Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/0378-4347(92)80420-U","article-title":"Determination of Vinca Alkaloids in mouse tissues by high-performance liquid chromatography","volume":"578","author":"Smet","year":"1992","journal-title":"J. Chromatogr. B"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/0092-8674(94)90212-7","article-title":"Disruption of the mouse mdr1a P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs","volume":"77","author":"Schinkel","year":"1994","journal-title":"Cell"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4131","DOI":"10.1172\/JCI70430","article-title":"P-glycoprotein ABCB1, a major player in drug handling by mammals","volume":"123","author":"Borst","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1111\/j.1469-7793.1998.333bq.x","article-title":"Protein kinase C phosphorylation disengages human and mouse-1a P-glycoproteins from influencing the rate of activation of swelling-activated chloride currents","volume":"508","author":"Bond","year":"1998","journal-title":"J. Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1038\/sj.onc.1204065","article-title":"Mdr1b facilitates p53-mediated cell death and p53 is required for Mdr1b upregulation in vivo","volume":"20","author":"Lecureur","year":"2001","journal-title":"Oncogene"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"15387","DOI":"10.1074\/jbc.273.25.15387","article-title":"Wild-type p53-mediated induction of rat mdr1b expression by the anticancer drug daunorubicin","volume":"273","author":"Zhou","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1093\/carcin\/20.3.407","article-title":"Reactive oxygen species participate in mdr1b mRNA and P-glycoprotein overexpression in primary rat hepatocyte cultures","volume":"20","author":"Ziemann","year":"1999","journal-title":"Carcinogenesis"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1021\/mp800050q","article-title":"Effects of monoglycerides on P-glycoprotein: Modulation of the activity and expression in Caco-2 cell monolayers","volume":"5","author":"Barta","year":"2008","journal-title":"Mol. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2302","DOI":"10.1248\/bpb.31.2302","article-title":"Evaluation of carbamazepine pharmacokinetic profiles in mice with kainic acid-induced acute seizures","volume":"31","author":"Nishimura","year":"2008","journal-title":"Biol. Pharm. Bull."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1124\/mol.108.050492","article-title":"Inhibition of P-glycoprotein-mediated paclitaxel resistance by reversibly linked quinine homodimers","volume":"75","author":"Pires","year":"2009","journal-title":"Mol. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.intimp.2008.11.007","article-title":"P-glycoprotein function in peripheral T lymphocyte subsets of myasthenia gravis patients: Clinical implications and influence of glucocorticoid administration","volume":"9","author":"Tanaka","year":"2009","journal-title":"Int. Immunopharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.ejps.2005.12.011","article-title":"Insulin in flavin-containing monooxygenase regulation Flavin-containing monooxygenase and cytochrome P450 activities in experimental diabetes","volume":"28","author":"Benko","year":"2006","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2660","DOI":"10.1152\/ajpheart.00489.2006","article-title":"Streptozotocin-induced diabetes progressively increases blood-brain barrier permeability in specific brain regions in rats","volume":"291","author":"Huber","year":"2006","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1124\/pr.57.2.4","article-title":"The blood-brain barrier\/neurovascular unit in health and disease","volume":"57","author":"Hawkins","year":"2005","journal-title":"Pharmacol. Rev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neulet.2006.09.010","article-title":"Decreased blood-brain barrier permeability to fluorescein in streptozotocin-treated rats","volume":"411","author":"Hawkins","year":"2007","journal-title":"Neurosci. Lett."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.ejphar.2007.01.062","article-title":"Attenuated function and expression of P-glycoprotein at blood\u2013brain barrier and increased brain distribution of phenobarbital in streptozotocin-induced diabetic mice","volume":"561","author":"Liu","year":"2007","journal-title":"Eur. J. Pharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1254\/jphs.FP0040832","article-title":"Effects of first-and second-generation histamine-H1-receptor antagonists on the pentobarbital-induced loss of the righting reflex in streptozotocin-induced diabetic mice","volume":"97","author":"Kamei","year":"2005","journal-title":"J. Pharmacol. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1016\/j.neuroscience.2008.03.019","article-title":"Increased amyloid beta-peptide (1\u201340) level in brain of streptozotocin-induced diabetic rats","volume":"153","author":"Liu","year":"2008","journal-title":"Neuroscience"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"24248","DOI":"10.1016\/S0021-9258(18)35757-0","article-title":"Human P-glycoprotein transports cortisol, aldosterone, and dexamethasone, but not progesterone","volume":"267","author":"Ueda","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.exer.2006.09.012","article-title":"Up-regulation of P-glycoprotein expression by osmotic stress in rat sugar cataract","volume":"84","author":"Miyazawa","year":"2007","journal-title":"Exp. Eye Res."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/21\/1\/46\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T20:55:00Z","timestamp":1760216100000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/21\/1\/46"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,12,29]]},"references-count":43,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,1]]}},"alternative-id":["molecules21010046"],"URL":"https:\/\/doi.org\/10.3390\/molecules21010046","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,12,29]]}}}