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.
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).
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).
(I) Metabolomic Workflow (II) GC-MS and Nuclear Magnetic Resonance metabolomics reveals an excretory metabolic signature of RCC.
- “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).
Silva, B; Silva, R; Fernandes, C; de Pinho, PG; Remiao, F. 2020. Enantioselectivity on the absorption of methylone and pentedrone using Caco-2 cell line: Development and validation of an UHPLC method for cathinones quantification. TOXICOLOGY AND APPLIED PHARMACOLOGY, 395, DOI: 10.1016/j.taap.2020.114970
Mesquita, I; Ferreira, C; Moreira, D; Kluck, GEG; Barbosa, AM; Torrado, E; Dinis-Oliveira, RJ; Goncalves, LG; Beauparlant, CJ; Droit, A; Berod, L; Sparwasser, T; Bodhale, N; Saha, B; Rodrigues, F; Cunha, C; Carvalho, A; Castro, AG; Estaquier, J; Silvestre, R. 2020. The Absence of HIF-1 alpha Increases Susceptibility to Leishmania donovani Infection via Activation of BNIP3/mTOR/SREBP-1c Axis. Cell Reports, 30, DOI: 10.1016/j.celrep.2020.02.098
Haagsma JA, James SL, Castle CD, Dingels ZV, Fox JT, Hamilton EB, Liu Z, Lucchesi LR, Roberts NLS, Sylte DO, Adebayo OM, Ahmadi A, Ahmed MB, Aichour MTE, Alahdab F, Alghnam SA, Aljunid SM, Al-Raddadi RM, Alsharif U, Altirkawi K, Anjomshoa M, Antonio CAT, Appiah SCY, Aremu O, Arora A, Asayesh H, Assadi R, Awasthi A, Quintanilla BPA, Balalla S, Banstola A, Barker-Collo SL, Bärnighausen TW, Bazargan-Hejazi S, Bedi N, Behzadifar M, Behzadifar M, Benjet C, Bennett DA, Bensenor IM, Bhaumik S, Bhutta ZA, Bijani A, Borges G, Borschmann R, Bose D, Boufous S, Brazinova A, Rincon JCC, Cárdenas R, Carrero JJ, Carvalho F, Castañeda-Orjuela CA, Catalá-López F, Choi JYJ, Christopher DJ, Crowe CS, Dalal K, Daryani A, Davitoiu DV, Degenhardt L, De Leo D, De Neve JW, Deribe K, Dessie GA, deVeber GA, Dharmaratne SD, Doan LP, Dolan KA, Driscoll TR, Dubey M, El-Khatib Z, Ellingsen CL, El Sayed Zaki M, Endries AY, Eskandarieh S, Faro A, Fereshtehnejad SM, Fernandes E, Filip I, Fischer F, Franklin RC, Fukumoto T, Gezae KE, Gill TK, Goulart AC, Grada A, Guo Y, Gupta R, Haghparast Bidgoli H, Haj-Mirzaian A, Haj-Mirzaian A, hamadeh RR, Hamidi S, Haro JM, Hassankhani H, Hassen HY, Havmoeller R, Hendrie D, Henok A, Hijar M, Hole MK, Rad EH, Hossain N, Hostiuc S, Hu G, Igumbor EU, Ilesanmi OS, Iravni SSN, Islam SMS, Ivers RQ, Jacobsen KH, Jahanmehr N, Jakovljevic M, Jayatilleke AU, Jha RP, Jonas JB, Shushtari ZJ, Jozwiak JJ, Jürisson M, Kabir A, Kalani R, Kasaeian A, Kelbore AG, Kengne AP, Khader YS, Khafaie MA, Khalid N, Khan EA, Khoja AT, Kiadaliri AA, Kim YE, Kim D, Kisa A, Koyanagi A, Defo BK, Bicer BK, Kumar M, Lalloo R, Lam H, Lami FH, Lansingh VC, Leasher JL, Li S, Linn S, Lunevicius R, Machado FR, Magdy Abd El Razek H, Magdy Abd El Razek M, Mahotra NB, Majdan M, Majeed A, Malekzadeh R, Malik MA, Malta DC, Manda AL, Mansournia MA, Massenburg BB, Maulik PK, Meheretu HAA, Mehndiratta MM, Melese A, Mendoza W, Mengesha MM, Meretoja TJ, Teretoja A, Mestrovic T, Miazgowski T, Miller TR, Mini GK, Mirrakhimov EM, Moazen B, Mezerji NMG, Mohammadibakhsh R, Mohammed S, Molokhia M, Monasta L, Mondello S, Montero-Zamora PA, Moodley Y, Moosazadeh M, Moradi G, Moradi-Lakeh M, Morawska L, Moreno Vel squez I, Morrison SD, Moschos MM, Mousavi SM, Murthy S, Musa KI, Naik G, Najafi F, Nangia V, Nascimento BR, Ndwandwe DE, Negoi I, Nguyen TH, Nguyen SH, Nguyen LH, Nguyen HLT, Ningrum DNA, Nirayo YL, Ofori-Asenso R, Ogbo FA, Oh IH, Oladimeji O, Olagunju AT, Olagunju TO, Olivares PR, Orpana HM, Otstavnov SS, P A M, Pakhale S, Park EK, Patton GC, Pesudovs K, Phillips MR, Polinder S, Prakash S, Radfar A, Rafay A, Rafiei A, Rahimi S, Rahimi-Movaghar V, Rahman MA, Rai RK, Ramezanzadeh K, Rawaf S, Rawaf DL, Renzaho AMN, Resnikoff S, Rezaeian S, Roever L, Ronfani L, Roshandel G, Sabde YD, Saddik B, Salamati P, Salimi Y, Salz I, Samy AM, Sanabria J, Sanchez Riera L, Santric Milicevic MM, Satpathy M, Sawhney M, Sawyer SM, Saxena S, Saylan M, Schneider IJC, Schwebel DC, Seedat S, Sepanlou SG, Shaikh MA Shams-Beyranvand M, Shamsizadeh M, Sharif-Alhoseini M, Shiekh A, Shen J, Shigematsu M, Shiri M, Shiue I, Silva JP, Singh JA, Sinha DN, Soares Filho AM, Soriano JB, Soshnikov S, Soyiri IN, Starodubov VI, Stein DJ, Stokes MA, Sufiyan MB, Sunshine JE, Sykes BL, Tabarés-Seisdedos R, Tabb KM, Tehrani-Banihashemi A, Tessema GA, Thakur JS, Tran KB, Tran BX, Tudor Car L, Uthman OA, Uzochukwu BSC, Valdez PR, Varavikova E, Vasconcelos AMN, Venketasubramanian N, Violante FS, Vlassov V, Waheed Y, Wang YP, Wijeratne T, Winkler AS, Yadav P, Yano Y, Yenesew MA, Yip P, Yisma E, Yonemoto N, Younis MZ, Yu C, Zafar S, Zaidi Z, Zaman SB, Zamani M, Zhao Y, Zodpey S, Hay SI, Lopez AD, Mokdad AH, Vos T.. 2020. Burden of injury along the development spectrum: associations between the Socio-demographic Index and disability-adjusted life year estimates from the Global Burden of Disease Study 2017. INJURY PREVENTION, DOI: 10.1136/injuryprev-2019-043296
Silva, P; Mendes, RF; Fernandes, C; Gomes, AC; Ananias, D; Remiao, F; Borges, F; Valente, AA; Paz, FAA. 2020. Multifunctionality and cytotoxicity of a layered coordination polymer. DALTON TRANSACTIONS, 49, DOI: 10.1039/c9dt04211c
Sousa, A; Dinis-Oliveira, RJ. 2020. Pharmacokinetic and pharmacodynamic of the cognitive enhancer modafinil: Relevant clinical and forensic aspects. Substance Abuse, 41, DOI: 10.1080/08897077.2019.1700584