In vitro effects from atorvastatin and metformin on cell proliferation induced by dyslipidemic contexts in benign prostatic hyperplasia

Benign prostatic hyperplasia (BPH) is characterized by uncontrolled proliferation of mainly stromal elements, arise from a conjunction of multiple physiopathogenic factors. Among them, the metabolic syndrome components are strongly correlated to the risk of suffering from BPH and its aggressiveness,...

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Autores principales: Reinarz Torrado, KF, Martinez Piñerez, DE, Roldán Gallardo, FF, López Seoane, M, Maldonado, CA, Quintar , AA
Formato: Artículo revista
Publicado: Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología 2022
Materias:
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Acceso en línea:https://revistas.unc.edu.ar/index.php/med/article/view/38977
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id I10-R327-article-38977
record_format ojs
institution Universidad Nacional de Córdoba
institution_str I-10
repository_str R-327
container_title_str Revista de la Facultad de Ciencias Médicas de Córdoba
format Artículo revista
topic prostatic stromal cells
OxLDL
atorvastatin
metformin
Células estromales prostáticas
OxLDL
atorvastatina
metformina
.
spellingShingle prostatic stromal cells
OxLDL
atorvastatin
metformin
Células estromales prostáticas
OxLDL
atorvastatina
metformina
.
Reinarz Torrado, KF
Martinez Piñerez, DE
Roldán Gallardo, FF
López Seoane, M
Maldonado, CA
Quintar , AA
In vitro effects from atorvastatin and metformin on cell proliferation induced by dyslipidemic contexts in benign prostatic hyperplasia
topic_facet prostatic stromal cells
OxLDL
atorvastatin
metformin
Células estromales prostáticas
OxLDL
atorvastatina
metformina
.
author Reinarz Torrado, KF
Martinez Piñerez, DE
Roldán Gallardo, FF
López Seoane, M
Maldonado, CA
Quintar , AA
author_facet Reinarz Torrado, KF
Martinez Piñerez, DE
Roldán Gallardo, FF
López Seoane, M
Maldonado, CA
Quintar , AA
author_sort Reinarz Torrado, KF
title In vitro effects from atorvastatin and metformin on cell proliferation induced by dyslipidemic contexts in benign prostatic hyperplasia
title_short In vitro effects from atorvastatin and metformin on cell proliferation induced by dyslipidemic contexts in benign prostatic hyperplasia
title_full In vitro effects from atorvastatin and metformin on cell proliferation induced by dyslipidemic contexts in benign prostatic hyperplasia
title_fullStr In vitro effects from atorvastatin and metformin on cell proliferation induced by dyslipidemic contexts in benign prostatic hyperplasia
title_full_unstemmed In vitro effects from atorvastatin and metformin on cell proliferation induced by dyslipidemic contexts in benign prostatic hyperplasia
title_sort in vitro effects from atorvastatin and metformin on cell proliferation induced by dyslipidemic contexts in benign prostatic hyperplasia
description Benign prostatic hyperplasia (BPH) is characterized by uncontrolled proliferation of mainly stromal elements, arise from a conjunction of multiple physiopathogenic factors. Among them, the metabolic syndrome components are strongly correlated to the risk of suffering from BPH and its aggressiveness, although cellular mechanisms are slightly understood. This study aimed to evaluate in vitro the proliferative effect of Oxidized-LDL (OxLDL) and the possible inhibitory role of the main therapy used for metabolic syndrome in stromal cells primary cultures derived from patients with BPH. In this sense, prostatic stromal cells from 3 patients with BPH were isolated, cultured and replicated in MCDB with 10% BFS, and thereafter frozen at -80°C for subsequent protocols. The cells were stimulated for 24 hours with OxLDL (20μM), atorvastatin (20μM and 2,5μM), metformin (10mM and 2 mM) or combination of both inhibitors, using vehicles as controls. Cell proliferation was determined by the resazurin technique and cell count. Thus, OxLDL induced a remarkable cell proliferation increase (p<0.001), with uneven effects when treated with metformin and atorvastatin. Though atorvastatin promoted a mild inhibition on OxLDL cell proliferation, it was not statistically significant. On the contrary, the metformin anti-proliferative effects were statistically significant in both doses tested (p <0.01 vs OxLDL). The combination of metformin+atorvastatin, both at low and high doses, did not improve the anti-proliferative effect of metformin alone on cell proliferation induced by OxLDL. These results confirm the pathogenic effect of OxLDL, the resulting molecule in dyslipidemic contexts, in abnormal prostate growth and suggest a direct beneficial metformin action on prostatic stromal proliferation of BPH, in the dyslipidemic environment of metabolic syndrome.
publisher Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología
publishDate 2022
url https://revistas.unc.edu.ar/index.php/med/article/view/38977
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spelling I10-R327-article-389772024-04-15T16:14:45Z In vitro effects from atorvastatin and metformin on cell proliferation induced by dyslipidemic contexts in benign prostatic hyperplasia Impacto de la enfermedad pulmonar obstructiva crónica en la calidad de vida relacionada con la salud . Reinarz Torrado, KF Martinez Piñerez, DE Roldán Gallardo, FF López Seoane, M Maldonado, CA Quintar , AA prostatic stromal cells OxLDL atorvastatin metformin Células estromales prostáticas OxLDL atorvastatina metformina . Benign prostatic hyperplasia (BPH) is characterized by uncontrolled proliferation of mainly stromal elements, arise from a conjunction of multiple physiopathogenic factors. Among them, the metabolic syndrome components are strongly correlated to the risk of suffering from BPH and its aggressiveness, although cellular mechanisms are slightly understood. This study aimed to evaluate in vitro the proliferative effect of Oxidized-LDL (OxLDL) and the possible inhibitory role of the main therapy used for metabolic syndrome in stromal cells primary cultures derived from patients with BPH. In this sense, prostatic stromal cells from 3 patients with BPH were isolated, cultured and replicated in MCDB with 10% BFS, and thereafter frozen at -80°C for subsequent protocols. The cells were stimulated for 24 hours with OxLDL (20μM), atorvastatin (20μM and 2,5μM), metformin (10mM and 2 mM) or combination of both inhibitors, using vehicles as controls. Cell proliferation was determined by the resazurin technique and cell count. Thus, OxLDL induced a remarkable cell proliferation increase (p<0.001), with uneven effects when treated with metformin and atorvastatin. Though atorvastatin promoted a mild inhibition on OxLDL cell proliferation, it was not statistically significant. On the contrary, the metformin anti-proliferative effects were statistically significant in both doses tested (p <0.01 vs OxLDL). The combination of metformin+atorvastatin, both at low and high doses, did not improve the anti-proliferative effect of metformin alone on cell proliferation induced by OxLDL. These results confirm the pathogenic effect of OxLDL, the resulting molecule in dyslipidemic contexts, in abnormal prostate growth and suggest a direct beneficial metformin action on prostatic stromal proliferation of BPH, in the dyslipidemic environment of metabolic syndrome. La Hiperplasia Prostática Benigna (HPB) se caracteriza por la proliferación descontrolada de elementos principalmente estromales, resultado de la conjunción de múltiples factores fisiopatogénicos. Entre ellos, los componentes del síndrome metabólico se correlacionan fuertemente al riesgo de padecer HPB y a la agresividad de la misma, aunque los mecanismos celulares están poco esclarecidos. Nuestro objetivo fue evaluar in vitro el efecto proliferativo de la LDL oxidada (OxLDL) y el posible rol inhibitorio de las terapias usadas para el síndrome metabólico en cultivos primarios de células estromales provenientes de pacientes con HPB. Las células estromales prostáticas se aislaron de 3 pacientes con HPB, se cultivaron y replicaron en medio MCDB con 10%SFB y se congelaron a -80ºC para protocolos posteriores. Las células se estimularon por 24 horas con OxLDL (20μM), atorvastatina (20μM y 2,5μM), metformina (10mM y 2mM) o combinaciones de ambos inhibidores, usando vehículos como controles, determinándose la proliferación celular mediante la técnica de resazurina y por conteo celular. OxLDL indujo un marcado incremento en la proliferación celular (p<0.001), observándose efectos dispares cuando se trató con metformina y atorvastatina. Si bien atorvastatina promovió una leve disminución en la proliferación inducida por OxLDL, no resultó significativa estadísticamente. Por el contrario, la acción anti-proliferativa de metformina resultó notable, en ambas dosis ensayadas (p<0.01 vs. OxLDL). La combinación de metformina+atorvastatina, tanto a dosis bajas como altas, no mejoró la acción anti-proliferativa de metformina sola sobre la proliferación celular inducida por OxLDL. Estos resultados confirman el efecto patogénico de la OxLDL (molécula resultante de los contextos dislipidémicos) sobre el crecimiento anómalo de la próstata y sugieren una acción benéfica directa de metformina sobre la proliferación prostática estromal de la HPB en el entorno dislipidémico del síndrome metabólico. . Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología 2022-10-26 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion texto texto . https://revistas.unc.edu.ar/index.php/med/article/view/38977 Revista de la Facultad de Ciencias Médicas de Córdoba.; Vol. 79 No. Suplemento JIC XXIII (2022): Suplemento JIC XXIII Revista de la Facultad de Ciencias Médicas de Córdoba; Vol. 79 Núm. Suplemento JIC XXIII (2022): Suplemento JIC XXIII Revista da Faculdade de Ciências Médicas de Córdoba; v. 79 n. Suplemento JIC XXIII (2022): Suplemento JIC XXIII 1853-0605 0014-6722 http://creativecommons.org/licenses/by-nc/4.0