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.
abstract: 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.
authors.affiliation: The Key Laboratory of Modern Toxicology of Ministry of Education, Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, China. wyb@njmu.edu.cn.|The Center for Hygienic Analysis and Detection, Nanjing Medical University, Nanjing 211166, Jiangsu, China. wyb@njmu.edu.cn.
authors.forename: Yubang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: The Key Laboratory of Modern Toxicology of Ministry of Education, Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, China. qh@njmu.edu.cn.|The Center for Hygienic Analysis and Detection, Nanjing Medical University, Nanjing 211166, Jiangsu, China. qh@njmu.edu.cn.
authors.forename: Heng
authors.initials: H
authors.lastname: Qin
authors.affiliation: The Key Laboratory of Modern Toxicology of Ministry of Education, Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, China. zcx@njmu.edu.cn.|The Center for Hygienic Analysis and Detection, Nanjing Medical University, Nanjing 211166, Jiangsu, China. zcx@njmu.edu.cn.
authors.forename: Chengxiang
authors.initials: C
authors.lastname: Zhang
authors.affiliation: The Key Laboratory of Modern Toxicology of Ministry of Education, Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, China. huanfei@njmu.edu.cn.|The Center for Hygienic Analysis and Detection, Nanjing Medical University, Nanjing 211166, Jiangsu, China. huanfei@njmu.edu.cn.
authors.forename: Fei
authors.initials: F
authors.lastname: Huan
authors.affiliation: The Key Laboratory of Modern Toxicology of Ministry of Education, Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, China. yanting@njmu.edu.cn.|The Center for Hygienic Analysis and Detection, Nanjing Medical University, Nanjing 211166, Jiangsu, China. yanting@njmu.edu.cn.
authors.forename: Ting
authors.initials: T
authors.lastname: Yan
authors.affiliation: The Key Laboratory of Modern Toxicology of Ministry of Education, Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, China. lulu_0219@njmu.edu.cn.|The Center for Hygienic Analysis and Detection, Nanjing Medical University, Nanjing 211166, Jiangsu, China. lulu_0219@njmu.edu.cn.
authors.forename: Lulu
authors.initials: L
authors.lastname: Zhang
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014750:Vincristine / Q000493:pharmacokinetics / Q000633:toxicity*; D014802:Vitamin A Deficiency / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D014750:Vincristine; C095122:multidrug resistance protein 3
keywords: P-glycoprotein; rhodamine 123; vincristine; vitamin A deficiency