Isoxazole based nucleosides induce autophagy through the production of ROS and the suppression of the β-catenin pathway in human colorectal carcinoma cells

Chemico-Biological Interactions, Год журнала: 2024, Номер unknown, С. 111285 - 111285

Опубликована: Окт. 1, 2024

Язык: Английский

LC-MS/MS-Based Concurrent Quantification of Cannabidiol and Melatonin in Mouse Plasma to Elucidate Complex PK Interactions

Pharmaceutics, Год журнала: 2024, Номер 16(12), С. 1511 - 1511

Опубликована: Ноя. 25, 2024

Objective: This study aimed to develop a quantitative analytical method for the simultaneous determination of cannabidiol (CBD) and melatonin (MT) in mouse plasma using protein precipitation coupled with LC-MS/MS. Additionally, this sought investigate impact CBD on pharmacokinetics MT mice method. Methods: Mouse samples were precipitated acetonitrile analyzed Kromasil 100-5-C8 (2.1 × 50 mm) column. Following single administration, thirty male ICR randomly assigned five groups: 2 mg/kg intravenously (i.v.), 10 orally (p.o.), + (10 10) p.o., 40) p.o. followed by i.v. Pharmacokinetic parameters calculated non-compartmental model interactions MT. Results: The calibration curves linear over range 1000 ng/mL. Co-administration high dose (40 mg/kg) reduced Cmax 57% control, while area under curve from 0.5 8 h (AUC(0.5-8h)) was 2.85-fold that MT-only group. When (2 administered alongside orally, AUC(0.5-8h) 1.54 times given alone. AUC positively correlated distribution elimination phases MT, negatively Conclusions: developed LC-MS/MS is robust suitable pharmacokinetic studies involving vivo effects are complex. High oral doses inhibit both intestinal absorption metabolic clearance resulting more smooth PK profile.

Язык: Английский

Exploring the Therapeutic Potential of Cannabidiol in U87MG Cells: Effects on Autophagy and NRF2 Pathway

Antioxidants, Год журнала: 2024, Номер 14(1), С. 18 - 18

Опубликована: Дек. 26, 2024

Cannabinoids include both endogenous endocannabinoids and exogenous phytocannabinoids, such as cannabidiol (CBD), have potential therapeutic agents in cancer treatment due to their selective anticancer activities. CBD exhibits antioxidant pro-oxidant effects depending on its concentration cell types. These properties allow influence oxidative stress responses potentially enhance the efficacy of antitumor therapies. In this study, we treated U87MG glioma cells with low dose (1 μM) evaluated molecular effects. Our findings indicate that reduced viability by 20% (p < 0.05) through alteration mitochondrial membrane potential. The redox status caused an attempt rescue functionality nuclear localization GABP transcription factor involved mitochondria biogenesis. Moreover, increase autophagic flux, supported Beclin-1 ratio LC3-II/LC3-I. Due alteration, pro-apoptotic proteins were induced without activating apoptotic effectors Caspase-3 or Caspase-7. study NRF2 ubiquitin-binding protein p62 expression revealed levels CBD-treated cells. conclusion, low-dose makes more vulnerable cytotoxic effects, reducing dynamics while increasing flux systems. This explains mechanisms which respond treatment. highlight CBD, suggesting modulating autophagy pathways could represent a promising strategy for glioblastoma

Язык: Английский