A5039008828- Drug-Induced Hepatotoxicity and Protection
- Pharmacogenetics and Drug Metabolism
- Blood disorders and treatments
- Drug-Induced Adverse Reactions
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Drug Transport and Resistance Mechanisms
- Tryptophan and brain disorders
- Pharmacological Effects and Toxicity Studies
- Immune Cell Function and Interaction
- Inflammatory mediators and NSAID effects
- Nitric Oxide and Endothelin Effects
- Immune Response and Inflammation
- Pharmacological Receptor Mechanisms and Effects
- Computational Drug Discovery Methods
- Monoclonal and Polyclonal Antibodies Research
- Receptor Mechanisms and Signaling
- Cytokine Signaling Pathways and Interactions
- Pharmacological Effects of Natural Compounds
- Antibiotics Pharmacokinetics and Efficacy
- Pneumocystis jirovecii pneumonia detection and treatment
- Pharmaceutical studies and practices
- T-cell and B-cell Immunology
- Urticaria and Related Conditions
- HIV/AIDS drug development and treatment
- Mast cells and histamine
University of Toronto
2016-2025
Osaka University of Pharmaceutical Sciences
2019
Safer Medicines Trust
2018
Canada Research Chairs
2014
Instituto Politécnico Nacional
2014
Center for Research and Advanced Studies of the National Polytechnic Institute
2014
University of Liverpool
2000-2013
3M (United States)
2010-2013
Eli Lilly (United States)
2008
University of Guelph
2003-2006
To determine whether differences in in-vitro detoxification of sulfonamide-reactive metabolites can be detected among the lymphocytes from controls, patients with sulfonamide hypersensitivity reactions, and nonhypersensitivity reactions to agents.In-vitro toxicity assay on lymphocytes.Clinics for adverse drug an adult pediatric tertiary care center.Peripheral blood were obtained 46 normal volunteers 76 referred clinic assessment agents. Thirty-one had clinical histories consistent a...
Clozapine was oxidized to a reactive intermediate by HOCI, which is the major oxidant produced activated neutrophils. A mass spectrum obtained of this using flow system in reactants were fed into mixing chamber and products flowed directly Sciex API III spectrometer. The observed at m/z 325, 2 units less than protonated molecular ion parent drug. This reacted with water form several 343. same oxidation clozapine combination myeloperoxidase, hydrogen peroxide chloride ion. trapped glutathione...
The mechanism of idiosyncratic drug-induced liver injury (IDILI) remains poorly understood, to a large degree because the lack valid animal model. Recently, we reported an model in which treatment female C57BL/6 mice with amodiaquine (AQ) resulted mild delayed onset and resolution despite continued treatment. Such adaptation is common outcome IDILI caused by drugs that can cause failure. We had hypothesized most immune-mediated represents immune tolerance. In this study found AQ Cbl-b(-/-)...
Isoniazid (INH)-induced hepatotoxicity remains one of the most common causes drug-induced idiosyncratic liver injury and failure. This form is not believed to be immune-mediated because it usually associated with fever or rash, does recur more rapidly on rechallenge, previous studies have failed identify anti-INH antibodies (Abs). In this study, we found Abs present in sera 15 19 cases INH-induced Anti-INH were 8 sera; 11 had anti–cytochrome P450 (CYP)2E1 Abs, 14 against CYP2E1 modified by...
Oral terbinafine treatment for superficial fungal infections of toe and fingernails is associated with a low incidence (1:45000) hepatobiliary dysfunction. Due to the rare unpredictable nature this adverse drug reaction, mechanism toxicity has been hypothesized be either an uncommon immunological or metabolically mediated effect. However, there little evidence support mechanism, toxic metabolites have not identified. We incubated both rat human liver microsomal protein in presence GSH were...
Among the most serious side effects of sulfonamides are hypersensitivity reactions, pathogenesis which has been suggested to be mediated by reactive metabolites. We have previously demonstrated dose-related covalent binding and toxicity intermediates generated a murine hepatic microsomal activating system. hypothesized that hydroxylamine (H/A) metabolites might likely candidates for mediating such toxicity; accordingly, we synthesized chemically H/As sulfadiazine sulfamethoxazole. Synthesis...
Dapsone is an effective anti-inflammatory agent in conditions which inflammation mediated by neutrophils. also has been associated with agranulocytosis. We found that neutrophils, had activated a phorbol ester or opsonized zymosan, oxidized dapsone to its nitroderivative. It appears as if this due oxidation of myeloperoxidase the hydroxylamine, followed nonenzymatic hydroxylamine The can be isolated ascorbic acid added incubations. Monocytes contain and mononuclear leukocytes metabolize...
Isoniazid (INH) is associated with serious liver injury and autoimmunity. Classic studies in rats indicated that a reactive metabolite of acetylhydrazine responsible for the covalent binding toxicity INH. Studies rabbits suggested hydrazine might be toxic species. However, these models involved acute high doses INH, INH-induced humans has very different features than such animal models. In this study, we demonstrated INH itself can covalently bind mice also to human microsomes. Covalent...
Nevirapine (NVP) treatment is associated with a significant incidence of skin rash in humans, and it also causes similar immune-mediated Brown Norway (BN) rats. We have shown that the sulfate major oxidative metabolite, 12-OH-NVP, covalently binds skin. The fact metabolite responsible for covalent binding does not prove rash. used various inhibitors sulfation to test whether this reactive Salicylamide (SA), which depletes 3'-phosphoadenosine-5'-phosphosulfate (PAPS) liver, significantly...