title: Diffusion Efficiency and Bioavailability of Resveratrol Administered to Rat Brain by Different Routes: Therapeutic Implications.
abstract: Resveratrol possesses anti-tumor activities against central nervous system (CNS) tumors in vitro but has not yet been used clinically due to its low bioavailability, particularly in the CNS. This study thus aimed to elucidate brain bioavailability of trans-resveratrol by monitoring brain concentrations and dwell times following administration of resveratrol through intragastric, intraperitoneal, external carotid artery/ECA and intrathecal routes. In parallel, we evaluated the biological responses of rat RG2 glioblastoma cells as well as RG2-formed rat intracranial glioblastomas treated with resveratrol via intrathecal administration. The results revealed that resveratrol was detected in rat brains except when administered systemically. Intrathecal administration of reseveratrol led to abundant apoptotic foci and increased staining of the autophagy proteins, LC-3 and Beclin-1 and shrinkage of the intracranial tumors. In conclusion, the BBB penetrability of resveratrol is remarkably increased by intracthecal administration. Regular short-term resveratrol treatments suppress growth and enhance autophagic and apoptotic activities of rat RG2 glioblastoma cells in vitro and in vivo. Therefore, intrathecal administration of resveratrol could be an optimal intervention approach in the adjuvant management of brain malignancies.
authors.affiliation: Liaoning Laboratory of Cancer Genomics and Department of Cell Biology, College of Basic Medical Sciences, Dalian Medical University, 9 West Section, Lvshun South Road, Dalian, 116044, China.
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Shu
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Wang
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.forename: Xue
authors.initials: X
authors.lastname: Song
authors.forename: Shun
authors.initials: S
authors.lastname: Shi
authors.forename: Jia-Yao
authors.initials: JY
authors.lastname: Gu
authors.forename: Mo-Li
authors.initials: ML
authors.lastname: Wu
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Chen
authors.forename: Qing-You
authors.initials: QY
authors.lastname: Kong
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage*; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D001932:Brain Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005909:Glioblastoma / Q000188:drug therapy*; D014453:Glucuronosyltransferase / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage*
chemical_list: D016588:Anticarcinogenic Agents; D013267:Stilbenes; D014453:Glucuronosyltransferase; D000077185:Resveratrol