Dataset Information

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.

SUBMITTER: Shu XH

PROVIDER: S-EPMC4404447 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Diffusion Efficiency and Bioavailability of Resveratrol Administered to Rat Brain by Different Routes: Therapeutic Implications.

Shu Xiao-Hong XH Wang Li-Li LL Li Hong H Song Xue X Shi Shun S Gu Jia-Yao JY Wu Mo-Li ML Chen Xiao-Yan XY Kong Qing-You QY Liu Jia J

Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 20150401 2

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 response ...[more]

PMID: 25588581

Similar Datasets

Project description:BACKGROUND:Placebo effects on pain have been found to vary in size for different routes of medication administration (e.g. oral vs. injection). This has important implications for both clinical research and practice. To enhance our understanding of these differential placebo effects, research on the underlying expectations about multiple routes and symptoms other than pain is vital. METHODS:A cross-sectional, Internet-based survey was conducted in a representative sample of the Dutch population (n = 508). Respondents rated the expected effectiveness of pain- and itch-relieving medication in six forms, representing oral, injection and topical routes of administration. RESULTS:Injected medication was expected to be most effective for relieving pain, and topical medication for relieving itch. Furthermore, exploratory analyses showed that injections were expected to have the most rapid onset and long-lasting effects, and to be most frightening and expensive, while topical medication was expected to be the safest and the easiest to use, and oral medication was expected to have the most side effects. Higher expected effectiveness was moderately associated with expectations of more rapid onset and long-lasting effects, and better safety and ease of use. Associations of expected effectiveness with respondent characteristics (e.g. medication use and personality characteristics) were statistically small or nonsignificant. CONCLUSIONS:Expected effectiveness of medication differed depending on route of administration and targeted symptom. These findings have important implications for the design and interpretation of clinical trials and suggest that medication effects might be enhanced by prescribing medicine via the route that patients expect to be most effective for their complaint. SIGNIFICANCE:Differences in the expected effectiveness of medication depend on the route of administration (oral, injection, topical) and targeted symptom (pain, itch). These findings have important implications for clinical practice and the design and interpretation of clinical trials.

Project description:BackgroundIdiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease. Whether extracellular vesicles are effective in treating IPF and what is the optimal administrative route is not clear. Our previous studies have shown that immunity and matrix regulatory cells (IMRCs) derived from human embryonic stem cells can safely treat lung injury and fibrosis in mouse models, and its mechanism of action is related to the paracrine effect. In this study, we investigated the therapeutic effects of IMRC-derived extracellular vesicles (IMRC-EVs) on a bleomycin-induced pulmonary fibrosis mouse model and explored the optimal route of administration.MethodsTo study the biodistribution of IMRC-EVs after administration via different routes, NIR labeled-IMRC-EVs were delivered by intratracheal (IT) or intravenous (IV) route, and in vivo imaging was acquired at different time points. The therapeutic effects of IMRC-EVs delivered by different routes were analyzed by assessing histology, lung function, cytokines levels, and transcriptome profiling. RNA-seq of lung tissues was performed to investigate the mechanisms of EV treatment through IT or IV administrations.ResultsIMRC-EVs mainly reserved in the liver and spleen when administrated via IV route; and mainly retained in the lungs via the IT route. IMRC-EVs administrated via both routes demonstrated a therapeutic effect as attenuated pulmonary fibrosis, improved lung function, and histological parameters. Based on our RNA-seq results, different pathways may be affected by IMRC-EVs administrated via IT or IV routes. In addition, in vitro experiments showed that IMRC-EVs inhibited epithelial-to-mesenchymal transition induced by TGF-β.ConclusionIMRC-EVs administrated via IT or IV routes generate different biodistributions, but are both effective for the treatment of bleomycin-induced pulmonary fibrosis. The therapeutic mechanisms of IMRC-EVs administrated via different routes may be different.

Dataset Information

Diffusion Efficiency and Bioavailability of Resveratrol Administered to Rat Brain by Different Routes: Therapeutic Implications.

Publications

Diffusion Efficiency and Bioavailability of Resveratrol Administered to Rat Brain by Different Routes: Therapeutic Implications.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets