Clin Pharmacol Ther
UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Published: November 2023
In clinical trials of cannabidiol (CBD) for the treatment of seizures in patients with Dravet syndrome, Lennox-Gastaut syndrome, and tuberous sclerosis complex, elevations in serum alanine aminotransferase (ALT) > 3× the upper limit of normal were observed in some patents, but the incidence was much greater in patients who were receiving treatment with valproate (VPA) before starting CBD. To explore potential mechanisms underlying this interaction, we used DILIsym, a quantitative systems toxicology model, to predict ALT elevations in a simulated human population treated with CBD alone, VPA alone, and when CBD dosing was starting during treatment with VPA. We gathered in vitro data assessing the potential for CBD, the two major CBD metabolites, and VPA to cause hepatotoxicity via inhibition of bile acid transporters, mitochondrial dysfunction, and production of reactive oxygen species (ROS). Physiologically-based pharmacokinetic models for CBD and VPA were used to predict liver exposure. DILIsym simulations predicted dose-dependent ALT elevations from CBD treatment and this was predominantly driven by ROS production from the parent molecule. DILIsym also predicted VPA treatment to cause ALT elevations which were transient when mitochondrial biogenesis was incorporated into the model. Contrary to the clinical experience, simulation of 2 weeks treatment with VPA prior to introduction of CBD treatment did not predict an increase of the incidence of ALT elevations relative to CBD treatment alone. We conclude that the marked increased incidence of CBD-associated ALT elevations in patients already receiving VPA is unlikely to involve the three major mechanisms of direct hepatotoxicity.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1002/cpt.3004 | DOI Listing |
Diabetes Metab Syndr Obes
January 2025
Department of Ear, Nose and Throat, Beijing Hepingli Hospital, Beijing, People's Republic of China.
Objective: To evaluate the application value of STOP-Bang questionnaire (SBQ) in predicting abnormal metabolites.
Methods: Totally 121 patients were included into the study and filled the questionnaires, and their clinical data were collected at the same time. These patients were grouped according to the questionnaire scores.
Toxicol Rep
June 2025
Department of Animal Sciences, Faculty of Agriculture, University of Zabol, Sistan 98661-5538, Iran.
This study aimed to investigate the effects of dietary methionine (Met) supplementation on performance, immunity, and meat quality in growing Japanese quail exposed to aflatoxin B (AFB)-contaminated diets. Nine experimental diets were formulated, incorporating three levels of dietary Met (5.0, 6.
View Article and Find Full Text PDFAust Vet J
January 2025
Small Animal Specialist Hospital, Adelaide, South Australia, Australia.
This report describes the development of oesophagitis and oesophageal stricture in a dog secondary to anaphylaxis. A 9-month-old male entire Brussels Griffon presented in anaphylactic shock after exposure to Hymenoptera species (Sp). The dog had a history of an anaphylactic reaction after exposure to Hymenoptera, successfully managed with antihistamines and dexamethasone.
View Article and Find Full Text PDFSports Med Health Sci
March 2025
Sports and Exercise Physiology Laboratory, Department of Physiology, University of Calcutta, University Colleges of Sciences and Technology, 92 A.P.C. Road, Kolkata, 700009, India.
The present investigation examined the influence of age and pubertal transition on magnitude of muscle damage and inflammatory response following high intensity incremental treadmill running till volitional exhaustion in sixty-four sedentary prepubertal ( = 32) and postpubertal ( = 32) boys who were randomly recruited in the study. Muscle damage and inflammatory markers like creatine kinase (CK), lactate dehydrogenase (LDH), alanine aminotransferase (ALT), aspartate aminotranferase (AST), C-Reactive Protein (CRP) and Interleukin-6 (IL-6) were estimated before and after exercise. Serum CK, LDH, AST, ALT, CRP and IL-6 levels significantly increased after exercise in both the groups in comparison to respective pre-exercise values.
View Article and Find Full Text PDFBiochem Biophys Rep
March 2025
Basic Medical Laboratory, People's Liberation Army Joint Logistic Support Force 920th Hospital, Kunming City, Yunnan Province, China.
Previous studies have confirmed that burns and scalds can lead to metabolic disorders in the liver. However, the effects of severe burns at various time points on liver lipid metabolism disorders, as well as the relationship between these disorders and liver function, metabolism, and infection, have not yet been investigated.This study established a SD rat scald model, macroscopic observation of weight changes, histological staining, Western blot detection of fat browning and metabolic indicators, reverse transcription quantitative polymerase chain reaction analysis of the expression of liver new fat generation genes, determination of liver function and inflammatory indicators.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!
© LitMetric 2025. All rights reserved.