Toxicology covers all the aspects related to the investigation into the adverse effects of chemicals and can be considered a basic and applied science. For this reason, the Postgraduate Program in Toxicology includes three major areas: Experimental Toxicology, Clinical Toxicology, and Toxicological Analysis. Research lines in these three major areas allow incorporation of the different specialties that make up the many faces of Toxicology, as well as rising innovations in the area.
1. EXPERIMENTAL TOXICOLOGY. Researchers in Experimental Toxicology conduct studies to elucidate mechanisms and to evaluate the effects of toxic chemicals.
2. CLINICAL TOXICOLOGY. Researchers in Clinical Toxicology address the prevention and diagnosis of human poisoning by airborne, waterborne, and foodborne contaminants or by chemical substances used as medicines.
3.TOXICOLOGICAL ANALYSIS. Toxicological Analysis covers therapeutic monitoring, biological monitoring, doping control, drug addiction control, and non-biological analyses of samples obtained from air, food, water, and soil, among others.
2. CLINICAL TOXICOLOGY. Researchers in Clinical Toxicology address the prevention and diagnosis of human poisoning by airborne, waterborne, and foodborne contaminants or by chemical substances used as medicines.
3.TOXICOLOGICAL ANALYSIS. Toxicological Analysis covers therapeutic monitoring, biological monitoring, doping control, drug addiction control, and non-biological analyses of samples obtained from air, food, water, and soil, among others.
Specific topics include:
– Environmental neurotoxins, redox state in neurological diseases, mitochondrial dysfunction;
– Neurotoxicology, neuroprotection strategies;
– Biochemical toxicology and mechanisms of toxicity;
– Environmental genotoxicity;
– Metabolism of natural products;
– Characterization of animal toxins;
– Toxicology of metals;
– Gene/environment interactions;
– Evaluation of antigenotoxic and antimutagenic activities of bioactive compounds present in the diet;
– Nutrigenomics;
– Interactions between food nutrients and drugs;
– Pharmacokinetics of chiral drugs;
– Clinical aspects of drug toxicology;
– Method development for analysis of illicit drugs;
– Method development for analysis of metals in biological specimens and speciation analysis;
– Biomonitoring studies;
– Pharmaceutical analysis (metabolites and new biomarkers);
– Toxicoproteomics;
– Evaluation of toxic metals in food samples.
– Environmental neurotoxins, redox state in neurological diseases, mitochondrial dysfunction;
– Neurotoxicology, neuroprotection strategies;
– Biochemical toxicology and mechanisms of toxicity;
– Environmental genotoxicity;
– Metabolism of natural products;
– Characterization of animal toxins;
– Toxicology of metals;
– Gene/environment interactions;
– Evaluation of antigenotoxic and antimutagenic activities of bioactive compounds present in the diet;
– Nutrigenomics;
– Interactions between food nutrients and drugs;
– Pharmacokinetics of chiral drugs;
– Clinical aspects of drug toxicology;
– Method development for analysis of illicit drugs;
– Method development for analysis of metals in biological specimens and speciation analysis;
– Biomonitoring studies;
– Pharmaceutical analysis (metabolites and new biomarkers);
– Toxicoproteomics;
– Evaluation of toxic metals in food samples.
RESEARCH LINES: EXPERIMENTAL TOXICOLOGY
Professor Antônio Cardozo dos Santos
Email: acsantos@fcfrp.usp.br
Neurotrophic modulation as a strategy for neuroprotection: Investigation of the molecular mechanisms involved in neurodegenerative diseases and in chemically-induced neurotoxicity, and evaluation of the neurotrophic potential of natural and synthetic compounds as a strategy of neuroprotection and treatment. For this purpose, experimental models of chemically-induced neuropathies and experimental models of Parkinson´s and Alzheimer´s diseases are used.
Email: acsantos@fcfrp.usp.br
Neurotrophic modulation as a strategy for neuroprotection: Investigation of the molecular mechanisms involved in neurodegenerative diseases and in chemically-induced neurotoxicity, and evaluation of the neurotrophic potential of natural and synthetic compounds as a strategy of neuroprotection and treatment. For this purpose, experimental models of chemically-induced neuropathies and experimental models of Parkinson´s and Alzheimer´s diseases are used.
Professor Daniel Junqueira Dorta
Email: djdorta@ffclrp.usp.br
Biochemical Toxicology: Evaluation of mitochondrial and cellular changes induced by xenobiotics as a model to unveil their toxic mechanisms of action. The research focuses the study of cellular and molecular mechanisms by which exogenous substances, including medicinal drugs, natural substances, and industrial and environmental pollutants interfere with mitochondrial metabolism and its possible implications in several diseases; as well as the use of these changes as biomarkers of effect from exposure to toxic substances.
Email: djdorta@ffclrp.usp.br
Biochemical Toxicology: Evaluation of mitochondrial and cellular changes induced by xenobiotics as a model to unveil their toxic mechanisms of action. The research focuses the study of cellular and molecular mechanisms by which exogenous substances, including medicinal drugs, natural substances, and industrial and environmental pollutants interfere with mitochondrial metabolism and its possible implications in several diseases; as well as the use of these changes as biomarkers of effect from exposure to toxic substances.
Professor Danielle Palma de Oliveira
Email: dpalma@usp.br
Ecogenotoxicological evaluation of environmental chemicals: Evaluation of the genotoxic, mutagenic, and teratogenic potential of chemicals that could be released into the environment, using different endpoint in Salmonella thyphimurium, human cell culture, and early stages of Zebrafish. These essays are complemented with ecotoxicological studies using aquatic organisms and the determination of compounds in environmental samples, aiming at the Risk Assessment. Additionally, we are developing 3D cultures of skin and hepatic cells, in order to obtain more reliable results considering human health.
Email: dpalma@usp.br
Ecogenotoxicological evaluation of environmental chemicals: Evaluation of the genotoxic, mutagenic, and teratogenic potential of chemicals that could be released into the environment, using different endpoint in Salmonella thyphimurium, human cell culture, and early stages of Zebrafish. These essays are complemented with ecotoxicological studies using aquatic organisms and the determination of compounds in environmental samples, aiming at the Risk Assessment. Additionally, we are developing 3D cultures of skin and hepatic cells, in order to obtain more reliable results considering human health.
Professor Eliane Candiani Arantes Braga
Email: ecabraga@fcfrp.usp.br
Biochemical, Molecular, and Functional Characterization of Animals Toxins: Purification of biologically active compounds present in scorpion, snake, and ant venoms, as well as in the toad poisons, by chromatographic methods. Analysis of transcriptomes and proteomes of animal venoms. Biochemical and molecular characterization of the isolated toxins by determining the amino acid sequence, molecular mass, isoelectric point, and enzymatic activities (proteases, hyaluronidases, phospholipases, phosphodiesterases, and L-amino acid oxidases). Evaluation of its actions on ion channels, hemostatic system, inflammatory process, and other biological systems, aiming at the identification of compounds that can be used as models for the development of new drugs or as pharmacological tools. The aim is also to obtain molecules with greater biotechnological potential by heterologous expression.
Email: ecabraga@fcfrp.usp.br
Biochemical, Molecular, and Functional Characterization of Animals Toxins: Purification of biologically active compounds present in scorpion, snake, and ant venoms, as well as in the toad poisons, by chromatographic methods. Analysis of transcriptomes and proteomes of animal venoms. Biochemical and molecular characterization of the isolated toxins by determining the amino acid sequence, molecular mass, isoelectric point, and enzymatic activities (proteases, hyaluronidases, phospholipases, phosphodiesterases, and L-amino acid oxidases). Evaluation of its actions on ion channels, hemostatic system, inflammatory process, and other biological systems, aiming at the identification of compounds that can be used as models for the development of new drugs or as pharmacological tools. The aim is also to obtain molecules with greater biotechnological potential by heterologous expression.
Professor Lusânia Maria Greggi Antunes
Email: lusania@fcfrp.usp.br
– Evaluation of antigenotoxic and antimutagenic effects of dietary bioactive compounds. The aim of the research group is to identify dietary bioactive compounds, mainly antioxidants, with antigenotoxic and antimutagenic potential in experimental models in vivo and in vitro. It has also been investigated the mechanisms involved in the protective effects of dietary bioactive compounds against genomic instability induced by chemical compounds.
– Nutrigenomics. The aim of this research group is to apply the “omics” technologies to elucidate the effects of dietary bioactive compounds on the methylation of DNA and the expression of genes related to the maintenance of health.
Email: lusania@fcfrp.usp.br
– Evaluation of antigenotoxic and antimutagenic effects of dietary bioactive compounds. The aim of the research group is to identify dietary bioactive compounds, mainly antioxidants, with antigenotoxic and antimutagenic potential in experimental models in vivo and in vitro. It has also been investigated the mechanisms involved in the protective effects of dietary bioactive compounds against genomic instability induced by chemical compounds.
– Nutrigenomics. The aim of this research group is to apply the “omics” technologies to elucidate the effects of dietary bioactive compounds on the methylation of DNA and the expression of genes related to the maintenance of health.
Professor Norberto Peporine Lopes
Email: npelopes@fcfrp.usp.br
Investigation of the secondary metabolism. Several actions for the development of bioactive natural products have been taken at the national and state level, in the majority ones that led to the identification of substances with therapeutic potential. A prerequisite for clinical use is the chemical characterization of active targets and also the elucidation of possible metabolites. In this context, our research aims the establishment of a working platform that envisions supporting pre-clinical studies applying biomimetic organometallic catalysis and in vitro metabolism. For this purpose, extensive support of Mass Spectrometry is used looking to contribute to the analysis of Brazilian Biodiversity.
Email: npelopes@fcfrp.usp.br
Investigation of the secondary metabolism. Several actions for the development of bioactive natural products have been taken at the national and state level, in the majority ones that led to the identification of substances with therapeutic potential. A prerequisite for clinical use is the chemical characterization of active targets and also the elucidation of possible metabolites. In this context, our research aims the establishment of a working platform that envisions supporting pre-clinical studies applying biomimetic organometallic catalysis and in vitro metabolism. For this purpose, extensive support of Mass Spectrometry is used looking to contribute to the analysis of Brazilian Biodiversity.
Professor Suely Vilela
Email: suvilela@usp.br
Animal venom and antivenom: Characterization, action mechanism, and biotechnological application. Isolation and biochemical characterization, including function and structure of the major toxic components present in animal venom; Search proteins and/or peptides with a biotechnological application seeking the obtainment of new drugs; To investigate the biochemical characteristics (molecular weight, amino acid composition, amino-terminal sequencing, isoelectric point, etc.), biological (activity on hemostasia, antitumoral effects, myotoxicity, phospholipases activity, hemorrhagic, edematogenesis, L-amino acid oxidase, etc.) and structural (determination of primary, secondary and tertiary structures) of those isolated venom compounds; Study the action mechanism of these components; Evaluate the in vitro antitumoral activity of these compounds in different types of cancer, seeking the obtainment of new drugs.
Email: suvilela@usp.br
Animal venom and antivenom: Characterization, action mechanism, and biotechnological application. Isolation and biochemical characterization, including function and structure of the major toxic components present in animal venom; Search proteins and/or peptides with a biotechnological application seeking the obtainment of new drugs; To investigate the biochemical characteristics (molecular weight, amino acid composition, amino-terminal sequencing, isoelectric point, etc.), biological (activity on hemostasia, antitumoral effects, myotoxicity, phospholipases activity, hemorrhagic, edematogenesis, L-amino acid oxidase, etc.) and structural (determination of primary, secondary and tertiary structures) of those isolated venom compounds; Study the action mechanism of these components; Evaluate the in vitro antitumoral activity of these compounds in different types of cancer, seeking the obtainment of new drugs.
RESEARCH LINES: CLINICAL TOXICOLOGY
Professor João Paulo Bianchi Ximemez
Email: joaopaulo.ximenez@usp.br
Clinical Pharmacokinetics and Pharmacogenomics: translational PK/PD (Pharmacokinetics-Pharmacodynamics) studies for patients with neurocryptococcosis, tuberculosis, HIV, and cancer.
Email: joaopaulo.ximenez@usp.br
Clinical Pharmacokinetics and Pharmacogenomics: translational PK/PD (Pharmacokinetics-Pharmacodynamics) studies for patients with neurocryptococcosis, tuberculosis, HIV, and cancer.
Professor Natália Valadares de Moraes
Email: nmoraes@fcfar.unesp.br
Drug Toxicology: Drug metabolism and kinetic disposition. Recognition of covariates (drug-drug interactions, clinical aspects, pharmacogenetics, exposure to xenobiotics) on the kinetic disposition of drugs under clinical use. Investigation of the role of drug transporters in the kinetic disposition and in the pharmacokinetics-pharmacodynamics relationship.
Email: nmoraes@fcfar.unesp.br
Drug Toxicology: Drug metabolism and kinetic disposition. Recognition of covariates (drug-drug interactions, clinical aspects, pharmacogenetics, exposure to xenobiotics) on the kinetic disposition of drugs under clinical use. Investigation of the role of drug transporters in the kinetic disposition and in the pharmacokinetics-pharmacodynamics relationship.
Professor Vera Lucia Lanchote
Email: lanchote@fcfrp.usp.br
Clinical Pharmacology with emphasis on studies of Pharmacokinetics, Pharmacokinetics-Pharmacodynamics (PK-PD) and Pharmacogenetics: Clinical Pharmacokinetics in infectious and inflammatory diseases; Maternal-fetal clinical Pharmacokinetics; Clinical Evaluation of CYP enzymes and drug transporters functions using probe cocktails.
Email: lanchote@fcfrp.usp.br
Clinical Pharmacology with emphasis on studies of Pharmacokinetics, Pharmacokinetics-Pharmacodynamics (PK-PD) and Pharmacogenetics: Clinical Pharmacokinetics in infectious and inflammatory diseases; Maternal-fetal clinical Pharmacokinetics; Clinical Evaluation of CYP enzymes and drug transporters functions using probe cocktails.
RESEARCH LINES: ANALYTICAL TOXICOLOGY
Professor Bruno Spinosa De Martinis
Email: martinis@usp.br
Analytical Methods for the Determination of Drugs of Abuse. Aims: 1) Develop analytical methodologies employing gas chromatography, extraction, and sample preparation techniques for the determination of licit and illicit abused drugs in biological samples; 2) Investigate the presence of drugs of abuse in alternative biological samples in vivo and postmortem cases; 3) Assess correlations between illicit drug abuse and violent deaths; 4) Study the analytical and medico-legal aspects of alcohol.
Email: martinis@usp.br
Analytical Methods for the Determination of Drugs of Abuse. Aims: 1) Develop analytical methodologies employing gas chromatography, extraction, and sample preparation techniques for the determination of licit and illicit abused drugs in biological samples; 2) Investigate the presence of drugs of abuse in alternative biological samples in vivo and postmortem cases; 3) Assess correlations between illicit drug abuse and violent deaths; 4) Study the analytical and medico-legal aspects of alcohol.
Professor Cristiane Masetto de Gaitani
Email: crisgai@fcfrp.usp.br
Analysis of drugs, metabolites, and biomarkers in biological matrices. Development and validation of methods for the analysis of drugs, metabolites, and biomarkers in biological matrices using capillary electrophoresis (CE) and high-performance liquid chromatography coupled to UV and Mass spectrometry detectors (LC-UV and LC-MC-MS). Sample preparation comprises the use of miniaturized extraction techniques, such as dispersive liquid-liquid microextraction (DLLME), solid-phase microextraction (SPME), and liquid phase microextraction (LPME). The methods are applied in biological matrices from volunteers or patients in treatment aiming at either therapeutic monitoring or disease diagnosis.
Email: crisgai@fcfrp.usp.br
Analysis of drugs, metabolites, and biomarkers in biological matrices. Development and validation of methods for the analysis of drugs, metabolites, and biomarkers in biological matrices using capillary electrophoresis (CE) and high-performance liquid chromatography coupled to UV and Mass spectrometry detectors (LC-UV and LC-MC-MS). Sample preparation comprises the use of miniaturized extraction techniques, such as dispersive liquid-liquid microextraction (DLLME), solid-phase microextraction (SPME), and liquid phase microextraction (LPME). The methods are applied in biological matrices from volunteers or patients in treatment aiming at either therapeutic monitoring or disease diagnosis.
Professor Fernando Barbosa Júnior
Email: fbarbosa@fcfrp.usp.br
Human Biomonitoring and Exposomics. Evaluation of populations exposed to several contaminants and their effects. Use of less invasive collection systems. Evaluation of new exposure markers and omic tools (proteomics and metabolomics) in mechanisms of toxicity. Establishment of reference values in the Brazilian population. Exposomics studies in Brazilian populations.
Toxicology of metals and metalloids. Toxicology of metals and metalloids. Exposure to metals and their effects in experimental models. Oxidative stress markers. Toxicology of omic systems and tools. Identification of new candidates for exposure and effect biomarkers using proteomics and metabolomics.
Emerging Contaminants: Exposure and Effects. Method development for the determination of Emerging Contaminants (metabolites) in biological fluids. Evaluation of exposure to ECs in distinct populations. In vitro and in vivo studies of the effects of exposure to ECs.
Email: fbarbosa@fcfrp.usp.br
Human Biomonitoring and Exposomics. Evaluation of populations exposed to several contaminants and their effects. Use of less invasive collection systems. Evaluation of new exposure markers and omic tools (proteomics and metabolomics) in mechanisms of toxicity. Establishment of reference values in the Brazilian population. Exposomics studies in Brazilian populations.
Toxicology of metals and metalloids. Toxicology of metals and metalloids. Exposure to metals and their effects in experimental models. Oxidative stress markers. Toxicology of omic systems and tools. Identification of new candidates for exposure and effect biomarkers using proteomics and metabolomics.
Emerging Contaminants: Exposure and Effects. Method development for the determination of Emerging Contaminants (metabolites) in biological fluids. Evaluation of exposure to ECs in distinct populations. In vitro and in vivo studies of the effects of exposure to ECs.
Professor Jonas Augusto Rizzato Paschoal
Email: paschoal@usp.br
Studies of residues of veterinary drugs in food. The objectives of this research involve the development and validation of analytical methods using modern instrumental techniques such as LC-MS/MS for the determination of veterinary drug residues in food. Furthermore, the research include experimental animal studies to evaluate the metabolic profile and residual depletion of important veterinary drugs, to estimate withdrawal periods. The planned activities aim to contribute to the studies focused on the issue of food toxicological safety due to the use of veterinary drugs in food animals.
Email: paschoal@usp.br
Studies of residues of veterinary drugs in food. The objectives of this research involve the development and validation of analytical methods using modern instrumental techniques such as LC-MS/MS for the determination of veterinary drug residues in food. Furthermore, the research include experimental animal studies to evaluate the metabolic profile and residual depletion of important veterinary drugs, to estimate withdrawal periods. The planned activities aim to contribute to the studies focused on the issue of food toxicological safety due to the use of veterinary drugs in food animals.
Professor Maria Eugênia Queiroz Nassur
Email: mariaeqn@ffclrp.usp.br
– Development of new stationary phases, such as molecularly imprinted polymers (MIP), restricted access material (RAM), immunosorbents, and conductor polymers (electropolymerization by cyclic voltammetry) for microextraction techniques (SPME, in-tube SPME, MEPS, and SBSE). Selective sorbents (stationary phases), such as immunosorbents (antigen-antibody interactions based on molecular recognition); poly(pyrrole) (porous structure with multifunctional properties); restricted access material (a biocompatible phase that enables the direct injection of biological fluids as well as the simultaneous exclusion of macromolecules by chemical diffusion barrier and drug pre-concentration), and molecularly imprinted polymers (molecular recognition- template molecule), have been tailored for micro extractions techniques (SPME, in-tube SPME, MEPS e SBSE) for analyses of drugs in biological fluids.
– Microextraction techniques coupled with liquid chromatography (in-tube SPME/LC-MS/MS). On-line in-tube SPME-performed continuous extraction, concentration, desorption, and injection using an autosampler, is usually used in combination with high-performance liquid chromatography and liquid chromatography-mass spectrometry. The main advantages of in-tube SPME are simplicity, rapidity, solvent elimination, high sensitivity, small sample volume, lower cost, and simple automation.
– Development and analytical validation of new chromatographic methods. Development and analytical validation of new chromatographic methods for determination of drugs in biological fluids for therapeutic drug monitoring and pharmacokinetic studies.
Email: mariaeqn@ffclrp.usp.br
– Development of new stationary phases, such as molecularly imprinted polymers (MIP), restricted access material (RAM), immunosorbents, and conductor polymers (electropolymerization by cyclic voltammetry) for microextraction techniques (SPME, in-tube SPME, MEPS, and SBSE). Selective sorbents (stationary phases), such as immunosorbents (antigen-antibody interactions based on molecular recognition); poly(pyrrole) (porous structure with multifunctional properties); restricted access material (a biocompatible phase that enables the direct injection of biological fluids as well as the simultaneous exclusion of macromolecules by chemical diffusion barrier and drug pre-concentration), and molecularly imprinted polymers (molecular recognition- template molecule), have been tailored for micro extractions techniques (SPME, in-tube SPME, MEPS e SBSE) for analyses of drugs in biological fluids.
– Microextraction techniques coupled with liquid chromatography (in-tube SPME/LC-MS/MS). On-line in-tube SPME-performed continuous extraction, concentration, desorption, and injection using an autosampler, is usually used in combination with high-performance liquid chromatography and liquid chromatography-mass spectrometry. The main advantages of in-tube SPME are simplicity, rapidity, solvent elimination, high sensitivity, small sample volume, lower cost, and simple automation.
– Development and analytical validation of new chromatographic methods. Development and analytical validation of new chromatographic methods for determination of drugs in biological fluids for therapeutic drug monitoring and pharmacokinetic studies.
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