Research Lab

Toxicology

Toxi_groupPhoto
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Research Interests

TOXICOLOGY group interests can be divided into 4 main topics: i) mechanistic toxicology, ii) modulation of xenobiotic toxicokinetics, iii) development of new treatments for intoxications, iv) metabonomics. Overall, it is our main goal to strengthen our most successful lines of research, in which the group has solid expertise and international recognition:

  • Toxicokinetic and mechanistic studies on drugs of abuse.
  • Safety evaluation of nanomaterials.
  • Evaluation of mixtures toxicology.
  • Search for new antidotes, from in silico to in vivo.
  • Modulation of pharmacokinetic factors to increase the safety of xenobiotics.
  • Use of metabolomic tools to dissect mechanisms of action and to find new and sensitive biomarkers of toxicity.
  • Refinement and replacement of in vivo by in vitro assays.

We also pursue the state of the art methodologies through establishment of new collaborations where new expertise can be acquired. Finally, financial support has been a continuous task, through development of scientific projects for national and international applications as well as through patent protection of our products.

Research Highlights
Discovery of an effective antidote for Amanita phalloides poisoning

Amanita phalloides is responsible for more than 90% of the fatalities occurring after mushrooms ingestion and no effective antidote is clinically available. In silico and in vivo studies proved that polymyxin B reversed the main toxicological features of α-amanitin, which point polymyxin B as a new potential antidote for A. phalloides intoxication (Garcia et al. ARCH TOXICOL, 2015, 89(12): 2305-2323; NATIONAL PATENT 108481; INTERNATIONAL PATENT PENDING; widely advertised in national mass media).

 

Discovery of an effective antidote for Amanita phalloides poisoning

Polymyxin B reverses the toxicity of α-amanitin

Metabolic profiling of potential urinary renal cell carcinoma (RCC) biomarkers using gas chromatography –mass spectrometry (GCMS) and nuclear magnetic resonance (NMR) platforms. The search for early diagnostic approaches for RCC owns great clinical and bi

A metabolic signature descriptive of RCC was unveiled, successfully distinguishing RCC patients from controls. It was demonstrated the value of a systematic metabolomics for the identification of urinary metabolic biomarkers in renal cancer (Monteiro et al. J CELL MOL MED_in press; Monteiro et al. SCI REPORTS, 2016, 6, 37275; Monteiro et al. FUTURE SCIENCE, 2015, 167-184).

 

Highligh_2

(I) Metabolomic Workflow (II) GC-MS and Nuclear Magnetic Resonance metabolomics reveals an excretory metabolic signature of RCC.

Representative Projects

  • “Poisoning the heart with anticancer drugs: is metabolic bioactivation or aging promotion the link to the cardiotoxicity of anticancer drugs?”, FCT-MCTES, Total funding : €199,933, Unit funding: €140,619, Vera Costa (PI).
  • “DESignBIOtecHealth -new technologies for three health challenges of modern societies: diabetes, drug abuse and kidney diseases”, FEDER-Portugal 2020, Total funding: €2.8M, Unit funding: €240,750, Félix Carvalho (Collaborator).
  • “Development of antidotes for Amanita phalloides intoxications, from in silico to the intoxicated patient”, FCT-MCTES, Total funding : € 199,637, Unit funding: €166,637, Félix Carvalho (PI).
  • CorkPlus -contribution of cork stoppers for chemical and sensory properties of bottled wine”. FEDER-Portugal 2020 and Amorim & Irmãos, SA, Total Funding: €1.2M, Unit funding: €483,423, Paula Guedes de Pinho (PI).
  • “ACCuseD renAl Cell Carcinoma Detection Renal Cancer detection: a translational metabolomics research based on Volatile Organic Compounds fingerprinting”, FCTMCTES, Total funding: €239,499, Unit funding: €164.018, Paula Guedes de Pinho (PI).

Selected Publications

Reis-Mendes, A; Carvalho, F; Remiao, F; Sousa, E; Bastos, MD; Costa, VM. 2019. The Main Metabolites of Fluorouracil. BIOMOLECULES, 9, DOI: 10.3390/biom9030098
Oliveira, C; Bagetta, D; Cagide, F; Teixeira, J; Amorim, R; Silva, T; Garrido, J; Remiao, F; Uriarte, E; Oliveira, PJ; Alcaro, S; Ortuso, F; Borges, F. 2019. Benzoic acid-derived nitrones: A new class of potential acetylcholinesterase inhibitors and neuroprotective agents. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 174, DOI: 10.1016/j.ejmech.2019.04.026
Couto, RAS; Costa, SS; Mounssef, B; Pacheco, JG; Fernandes, E; Carvalho, F; Rodrigues, CMP; Delerue-Matos, C; Braga, AAC; Goncalves, LM; Quinaz, MB. 2019. Electrochemical sensing of ecstasy with electropolymerized molecularly imprinted poly(o-phenylenediamine) polymer on the surface of disposable screen-printed carbon electrodes. SENSORS AND ACTUATORS B-CHEMICAL, 290, DOI: 10.1016/j.snb.2019.03.138
Fonseca, BM; Fernandes, R; Almada, M; Santos, M; Carvalho, F; Teixeira, NA; Correia-da-Silva, G. 2019. Synthetic cannabinoids and endometrial stromal cell fate: Dissimilar effects of JWH-122, UR-144 and WIN55,212-2. TOXICOLOGY, 413, DOI: 10.1016/j.tox.2018.11.006
Silva, T; Mohamed, T; Shakeri, A; Rao, PPN; da Silva, PS; Remiao, F; Borges, F. 2019. Repurposing nitrocatechols: 5-Nitro-alpha-cyanocarboxamide derivatives of caffeic acid and caffeic acid phenethyl ester effectively inhibit aggregation of tau-derived hexapeptide AcPHF6. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 167, DOI: 10.1016/j.ejmech.2019.02.006