Purpose: The amphiphilic block copolymer Pluronic P85 (P85) increases the permeability of the blood-brain barrier (BBB) with respect to a broad spectrum of drugs by inhibiting the drug efflux transporter, P-glycoprotein (Pgp). In this regard, P85 serves as a promising component for CNS drug delivery systems. To assess the possible effects of P85 on other transport systems located in the brain, we examined P85 interactions with the glucose (GLUT1) and monocarboxylate (MCT1) transporters.
Methods: Polarized monolayers of primary cultured bovine brain microvessel endothelial cells (BBMEC) were used as an in vitro model of the BBB. 3H-2-deoxy-glucose and 14C-lactate were selected as GLUT1 and MCT1 substrates, respectively. The accumulation and flux of these substrates added to the luminal side of the BBMEC monolayers were determined.
Results: P85 has little effect on 3H-2-deoxy-glucose transport. However, a significant decrease 14C-lactate transport across BBMEC monolayers is observed. Histology, immunohistochemistry, and enzyme histochemistry studies show no evidence of P85 toxicity in liver, kidney, and brain in mice.
Conclusions: This study suggests that P85 formulations do not interfere with the transport of glucose. This is, probably, due to compensatory mechanisms in the BBB. Regarding the transport of monocarboxylates, P85 formulations might slightly affect their homeostasis in the brain, however, without any significant toxic effects.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1023/b:pham.0000048189.79606.6e | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Bioactive materials from berberine-treated human bone marrow mesenchymal stem cells accelerate tooth extraction socket healing through the jaw vascular unit.
Sci China Life Sci
January 2025
Department of Oral and Maxillofacial Surgery, The Affiliated Stomatological Hospital of Nanjing Medical University; State Key Laboratory Cultivation Base of Research, Prevention and Treatment for Oral Diseases; Jiangsu Province Engineering Research Centre of Stomatological Translational Medicine, Nanjing Medical University, Nanjing, 210029, China.
Delayed tooth extraction socket (TES) healing can cause failure of subsequent oral implantation and increase socioeconomic burden on patients. Excessive amounts of M1 macrophages, apoptotic neutrophils (ANs), and neutrophil extracellular traps (NETs) impair alveolar bone regeneration during TES healing. In the present study, we first discovered that conditioned medium (CM) collected from berberine-treated human bone marrow mesenchymal stem cells (BBR-HB-CM) accelerated TES healing.
View Article and Find Full Text PDFTianxiangdan suppresses foam cell formation by enhancing lipophagy and reduces the progression of atherosclerosis.
In Vitro Cell Dev Biol Anim
January 2025
College of Traditional Chinese Medicine, Xinjiang Uygur Autonomous Region, Xinjiang Medical University, Urumqi, 830063, China.
The aim of this study is to assess the impact of Tianxiangdan (TXD) on lipophagy in foam cells and its underlying mechanism in treating atherosclerosis, particularly focusing on its efficacy in lowering blood lipids. In vivo, ApoE-/- atherosclerosis mouse models were established for group intervention. Blood lipid levels of the mice were measured, lipid deposition and autophagy levels in atherosclerotic plaques were assessed, and co-localization of lipid droplets and autophagosomes was examined.
View Article and Find Full Text PDF[Berberine regulates glucose and lipid metabolism via clock-controlled genes to ameliorate insulin resistance of hepatocytes].
Zhongguo Zhong Yao Za Zhi
December 2024
Jiangxi Province Key Laboratory of Traditional Chinese Medicine Etiopathogenisis & Research Center for Differentiation and Development of Traditional Chinese Medicine Basic Theory, Jiangxi University of Chinese Medicine Nanchang 330004,China.
This study aims to investigate the mechanism of berberine in regulating the metabolism network via clock-controlled genes represented by brain and muscle arnt-like 1(BMAL1) to ameliorate insulin resistance(IR) of hepatocytes in vitro. The HepG2 cell model of dexamethasone-induced IR(IR-HepG2) was established and treated with 5, 10, and 20 μmol·L~(-1) berberine, respectively, for 24 h. The glucose oxidase method and cell counting kit-8(CCK-8) assay were employed to measure extracellular glucose concentration and cell viability, respectively.
View Article and Find Full Text PDFResveratrol alleviates blast lung injury by modulating the epithelial sodium channel (ENaC) via the PI3K/AKT pathway.
Int Immunopharmacol
January 2025
The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang 450003, Henan, China; Clinical Medical Center of Tissue Engineering and Regeneration, Xinxiang Medical University, Xinxiang 450003, Henan, China. Electronic address:
Blast lung injury (BLI) is a major cause of death in blast injuries, largely due to pulmonary edema. Effective clearance of alveolar fluid is critical for resolving pulmonary edema, with the epithelial sodium channel (ENaC) playing a key role in this process. Resveratrol (RES), a natural compound with known antioxidant and anti-inflammatory properties, has shown promise in treating respiratory diseases.
View Article and Find Full Text PDFSulfur dioxide (SO) donors, a new gasotransmitter, improve erectile dysfunction after castration in a rat model.
Andrology
January 2025
Department of Pharmacology, Faculty of Pharmacy, Ankara University, Ankara, Turkey.
Background: Androgen deprivation is associated with erectile dysfunction (ED). In different animal models, sulfur dioxide (SO) donors NaSO and NaHSO reduced oxidative stress, fibrosis, and inflammation which contribute to the pathogenesis of androgen deprivation-induced ED, however the effect of SO donors on ED in castrated rats were not known.
Objective: To investigate the therapeutic effect of SO donors, NaSO/NaHSO, on ED in castrated rat model.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!