MEMBERS

ROXANA NOEMÍ PERONI

Associated Researcher – CONICET.

Assistant Proffesor – Chair of Pharmacology, Department of Pharmacology, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires.

MARTÍN ROMA

Universidad de Buenos Aires Doctoral Scholarship.

Pharmacist and Biochemist- Universidad de Buenos Aires.Assistant – Chair of Analytical Instrumental Chemistry, Department of Analytical Chemistry and Physicochemistry, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires.

ANA NATALIA SALAZAR SANABRIA

Doctor, Universidad Mayor de San Andrés (Bolivia).

LINES OF RESEARCH

INFLUENCE OF ABC EFFLUX TRANSPORTERS IN ANTIRETROVIRAL DRUGS TISSUE DISTRIBUTION

Anti-HIV drugs are the mainstay in AIDS patients treatment and the prevention of maternal-fetal transmission of the virus.Unfortunately, these drugs have high toxicity, therapeutic range is narrow and variations in the concentrations of these drugs in tissues can lead to therapeutic failure.In this line of research, the participation of ABCG2 transporter in the tissue distribution of drugs as the first-line antiretroviral drugs efavirenz and zidovudine is studied. The objective is to analyze the intestinal passage, transplacental and the central nervous system in order to optimize the therapeutic and avoid the toxic effects.

STUDY OF THE EFFECT ON ABC FAMILY OF VARIETIES OF ARUGULA AND ITS RELATIONSHIP WITH THE ANTIMUTAGENIC ROLE.

The aqueous extracts of arugula varieties Diplotaxis tenuifolia and Eruca vesicaria (Brassicaceae family) of Argentine flora have potential beneficial effects due to their chemopreventive capacity. This property leads to antigenotoxic, anticarcinogenic, and / or neuroprotective effects.The possible chemopreventive effects of these species could be due, at least in part, to their antioxidant capacity as well as their capacity to modulate the efflux transporters of the ABC family. Within this context, this recently created line aims to evaluate whether the sustained intake of Eruca vesicaria and Diplotaxis tenuifolia arugula modulate intestinal, hepatic and blood-brain barrier levels ABC transporters in mice.This study is relevant since these transporters influence the bioavailability of drugs and carcinogenic substances and the knowledge about the variations in their functionality helps to understand of how these natural products have the capacity to diminish toxic action of carcinogens.

MODULATION OF ABC TRANSPORTERS IN RESISTANT TUMOR CELLS BY CANNABINOIDS: BASIS FOR THE RATIONAL DESIGN OF COADJUVANT CHEMOTERAPY DRUGS.

This project is based on the hypothesis that, due to its ability to inhibit ABC transporters, cannabis and / or phytocannabinoids isolated from it could be useful to reverse the MDR associated with their induction and constitute potential coadjuvant agents in chemotherapy, studying the generation and / or reversion in human tumor cell lines.

PUBLICATIONS OF RELEVANCE

-Marcela M.López Nigro, Roxana N.Peroni,Iván Ayllón-Cabrera, Victoria E.Schiariti Lampropulos, Martín I.Roma, Marta A.Carballo. “In vivo antigenotoxic activity of Diplotaxis tenuifolia against cyclophosphamide-induced DNA damage: Relevance of modulation of hepatic ABC efflux transporters”. Mutation Research – Genetic Toxicology and Environmental Mutagenesis. Volume 836, Part B, December 2018, Pages 72-78

-Filia MF, Marchini T, Minoia JM, Roma MI, De Fino FT, Rubio MC, Copello GJ, Evelson PA, Peroni RN. Induction of ABCG2/BCRP restricts the distribution of zidovudine to the fetal brain in rats. Toxicol Appl Pharmacol. 330:74-83, 2017.

-Ayllón Cabrera, Iván; Schiariti Lampropulos, Victoria E.; Roma, Martin I.; Peroni, Roxana N.; Carballo, Marta A.; López Nigro, Marcela M. “In vivo antigenotoxic activity of rocket (Eruca vesicaria and Diplotaxis tenuifolia) against induced DNA damage.” X Congreso de Asociación LatinoAmericana de Mutagénesis, Carcinogénesis y Teratogénesis Ambiental  -ALAMCTA- (Montevideo, Uruguay) (2016). *Premiado por la Revista Científica “Mutation Research – Genetic Toxicology and Environmental Mutagenesis Section”.

-M.A. Carballo, M. Roma, I. Ayllón-Cabrera, M.M. López Nigro, R.N. Peroni. “Chronic intake of wild rocket leaf juice: Antigenotoxic effect and modulation of hepatic ABC efflux transporters”.  XIV International Congress of Toxicology (Merida, Yucatan, Mexico), 2016.

-Discovering new antiepileptic drugs addressing the transporter hypothesis of refractory epilepsy. Ligand-based approximations. Couyupetrou M, Di Ianni ME, Gantner ME, Pesce G, Peroni R, Bruno-Blanch LE & Talevi A. Protocols in Pharmacology/Toxicology, volumen: Antiepileptic Drug Discovery, Springer Protocols

-Roma MI, Hocht C, Chiappetta DA, Di Gennaro SS, Minoia JM, Bramuglia GF, Rubio MC, Sosnik A, Peroni RN. Tetronic® 904-containing polymeric micelles overcome the overexpression of ABCG2 in the blood-brain barrier of rats and boost the penetration of the antiretroviral efavirenz into the CNS. Nanomedicine (Lond). 2015 (15):2325-37.

-Minoia JM, Filia MF, Coppello G, Díaz L, Rubio MC, Peroni RN. “Relevancia de BCRP en la farmacocinética de Zidovudina y Lamivudina y su consecuencia sobre la genotoxicidad en hígado fetal de rata”. MEDICINA – Volumen 73 – (Supl. III), 2013

-Filia MF, Minoia JM, Marchini T, Evelson P, Coppello G, Díaz L, Rubio MC, Peroni RN. “BCRP restringe el pasaje de Zidovudina al cerebro fetal en ratas disminuyendo su toxicidad”. MEDICINA – Volumen 73 – (Supl. III), 2013

-Peroni RN, Abramoff T, Neuman I, Podestá EJ, Adler-Graschinsky E. Phytoestrogens enhance the vascular actions of the endocannabinoid anandamide in mesenteric beds of female rats. Int J Hypertens. 2012; 2012:647856.

-Peroni RN, Di Gennaro SS, Hocht C, Chiappetta DA, Rubio MC, Sosnik A, Bramuglia GF. Efavirenz is a substrate and in turn modulates the expression of the efflux transporter ABCG2/BCRP in the gastrointestinal tract of the rat. Biochem Pharmacol. 2011, 2(9):1227-33.

-Peroni, RN. INFLUENCIA DE LA PROTEÍNA DE RESISTENCIA DEL CÁNCER DE MAMA (BCRP) EN LA FARMACOCINÉTICA DE LOS ANTIRRETROVIRALES. Rev. Farm. vol. 153 nº 1-2: 91-102, 2011-Filia MF.; Di Gennaro SS.; Rubio MC.; Peroni RN. “Aumento de la expresión del transportador de eflujo BCRP en placenta por el tratamiento crónico con el antirretroviral AZT” MEDICINA – Volumen 70 (Supl. II):220, 2010.

-Peroni RN.; Hotch C.; Di Gennaro SS.; Chiappeta DA.; Rubio MC.; Sosnik A.; Bramuglia GF. “El tratamiento crónico con efavirenz disminuye su propia absorción intestinal y su distribución al sistema nervioso central al modificar los niveles de expresión del transportador de eflujo BCRP”. MEDICINA – Volumen 70 (Supl. II): 97, 2010.

FUNDING

PIP 11220120100499CO: Influence of the BCRP efflux transporter on the level of fetal exposure of nucleoside inhibitors of HIV reverse transcriptase.Director: Roxana Peroni.

UBACYT 20020170100637BA. Evaluación de productos presentes en la naturaleza que ejercen efecto antimutagénico y anticarcinogénico. Director: Marta Carballo; Participant: Roxana Peroni.

COLLABORATIONS

Alejandro Sosnik (Laboratory of Pharmaceutical Nanomaterials Science, Department of Materials Science & Engineering, Technion-Israel Institute of Technology, Haifa, Israel).

Guillermo Copello (Cátedra de Química Analítica Instrumental, Facultad de Farmacia y Bioquímica, UBA).

Pablo Evelson and team (IBIMOL- Cátedra de Química General Inorgánica, Facultad de Farmacia y Bioquímica, UBA).

Dra Marta Carballo -CIGETOX (Citogenética Humana y Genética Toxicológica, Departamento de Bioquímica Clínica de la Facultad de Farmacia y Bioquímica de la Universidad de Buenos Aires).