Valentina Squicciarini | Universidad de Chile (original) (raw)
Papers by Valentina Squicciarini
Physiological Reports, 2022
Acetylcholine (ACh) may be involved in the regulation of ovarian functions. A previous systemic s... more Acetylcholine (ACh) may be involved in the regulation of ovarian functions. A previous systemic study in rats showed that a 4-week, intrabursal local delivery of the ACh-esterase blocker Huperzine-A increased intraovarian ACh levels and changed ovarian follicular development, as evidenced by increased healthy antral follicle numbers and corpora lutea, as well as enhanced fertility. To further characterize the ovarian cholinergic system in the rat, we studied whether innervation may contribute to intraovarian ACh. We explored the cellular distribution of three muscarinic receptors (MRs; M1, M3, and M5), analyzed the involvement of MRs in ovarian steroidogenesis, and examined their roles in ovarian follicular development in normal conditions and in animals exposed to stressful conditions by employing the muscarinic antagonist, atropine. Denervation studies decreased ovarian norepinephrine, but ovarian ACh was not affected, evidencing a local, nonneuronal source of ACh. M1 was located on granulosa cells (GCs), especially in large antral follicles. M5 was associated with the ovarian vascular system and only traces of M3 were found. Ex vivo ovary organo-typic incubations showed that the MR agonist Carbachol did not modify steroid production or expression of steroid biosynthetic enzymes. Intrabursal, in vivo application of atropine (an MR antagonist) for 4 weeks, however, increased atresia of the secondary follicles. The results support the existence of an intraovarian cholinergic system in the rat ovary, located mainly in follicular GCs, which is not involved in steroid production but rather via MRs exerts trophic functions and regulates follicular atresia.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Journal of Natural Remedies, 2015
Encelia canescens Lam (nv: mancapaqi, mataloba, matalobo, mucle, or “coronilla de fraile”) is a 3... more Encelia canescens Lam (nv: mancapaqi, mataloba, matalobo, mucle, or “coronilla de fraile”) is a 30-80-cm high shrubby perennial plant that grows in the Atacama and Coquimbo regions of Chile up to 1,700 m above the sea. The present research was performed to examine the toxicological, antioxidant and antitumoural properties of aqueous and ethanol Encelia canescens Lam extracts. Our results revealed the presence of saponins, terpenes, flavonoids, coumarins and tannins. The total phenolic compound contents were 19±1.14 mg/g tannic acid in the aqueous extract and 23±1.60 mg/g tannic acid in the ethanol extract. The total flavonoid contents were 0.15±0.02 mg/g quercetinin the aqueous extract and 0.13±0.06 mg/g quercetinin the ethanol extract. Based on 2,2-diphenyl-1-picrylhydrazyl assays, the antioxidant capacities were 354±23 µmol trolox/100 g of the dry ethanol extract and 303±15 µmol trolox/100 g of the dry aqueous extract. Using 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulphonic ac...
Journal of Endocrinology
RFamide-related peptide (RFRP-3) is a regulator of GnRH secretion from the brain, but it can also... more RFamide-related peptide (RFRP-3) is a regulator of GnRH secretion from the brain, but it can also act in human ovary to influence steroidogenesis. We aimed to study the putative local role of RFRP-3 in the ovary and its potential participation in the development of a polycystic ovary phenotype induced by chronic sympathetic stress (cold stress). We used adult Sprague–Dawley rats divided into control and stressed groups. In both groups, we studied the effect of intraovarian exposure to RFRP-3 on follicular development and plasma ovarian steroid concentrations. We also tested the effect of RFRP-3 on ovarian steroid production in vitro. Chronic in vivo intraovarian exposure to RFRP-3 decreased basal testosterone concentrations and cold stress-induced progesterone production by the ovary. In vitro, RFRP-3 decreased hCG-induced ovarian progesterone and testosterone secretion. Immunohistochemistry and mRNA expression analysis showed a decrease in Rfrp and expression of its receptor in the...
Revista chilena de cardiología, 2011
Determinación del polimorfismo de CYP2C9*2 y su relación con la farmacocinética de acenocumarol e... more Determinación del polimorfismo de CYP2C9*2 y su relación con la farmacocinética de acenocumarol en voluntarios sanos.
![Research paper thumbnail of Oncol Lett Vol1 n3 page 549[1]](https://attachments.academia-assets.com/41221075/thumbnails/1.jpg)
](Polycyclic aromatic hydrocarbons (PAHs) contained in tobacco smoke acquire carcinogenicity follow... more Polycyclic aromatic hydrocarbons (PAHs) contained in tobacco smoke acquire carcinogenicity following their activation by xenobiotic-metabolizing enzymes to highly reactive metabolites. The cytochrome P4501A1 (CYP1A1) enzyme is central to the metabolic activation of these PAHs, and GSTM1 is the main enzyme responsible for its detoxiication.
Cuadernos médicos-sociales
En Chile la incidencia de leucemia es de 4.2/100.000 adultos al año. Dentro de ellas, 2,8/100.000... more En Chile la incidencia de leucemia es de 4.2/100.000 adultos al año. Dentro de ellas, 2,8/100.000 son leucemias agudas y 1,4/100.000 son leucemias crónicas. La quimioterapia para el cáncer ha progresado desde su introducción a la práctica clínica y constituye una modalidad terapéutica muy útil en las leucemias. Sin embargo, su uso se ve limitado por la imposibilidad de predecir la respuesta individual, por lo que la elección de la terapia suele ser en base a criterios médicos y de las guías clínicas establecidas. Esta variación inter-individual en la respuesta a un fármaco antineoplásico puede deberse a factores farmacocinéticos y/o farmacodinámicos, relacionados con otros factores genético-metabólicos, que se traducen en variantes polimórficas de las enzimas encargadas de la biotransformación de estos fármacos o receptores. Al respecto, se estima que la genética da cuenta entre un 20 a un 95% de la variabilidad en la respuesta terapéutica y toxicológica. De todas las drogas conocid...
During the last years science and technology of molecular diagnostic in order to assay personaliz... more During the last years science and technology of molecular diagnostic in order to assay personalized drug response or suitability to a specific pharmacological treatment experienced a rapid development. Therefore, with this subject clinical laboratory has evolved in complex technologies. The advances in pharmacogenetics allow us to point out that variability is the rule and not the exception, in majority of the pharmacological treatments, thus it is essential to incorporate in clinical laboratories this scientific tool through reliable assays. The implementation of PCR and/or RT-PCR analyses is affordable and the cost is justified considering costs for medication adjustment of dose The investment for the implementation of a Laboratory of Molecular Analysis in clinical centers should consider a necessary surface which must include: DNA extraction area, PCR room and a results processing area, according international guidelines, basic infraestructure and qualified staff. Therefore, it i...
Oncology letters, 2010
Polycyclic aromatic hydrocarbons (PAHs) contained in tobacco smoke acquire carcinogenicity follow... more Polycyclic aromatic hydrocarbons (PAHs) contained in tobacco smoke acquire carcinogenicity following their activation by xenobiotic-metabolizing enzymes to highly reactive metabolites. The cytochrome P4501A1 (CYP1A1) enzyme is central to the metabolic activation of these PAHs, and GSTM1 is the main enzyme responsible for its detoxification. CYP1A1 and GSTM1 polymorphisms were evaluated in 124 Chilean healthy controls and 48 oral cancer patients through PCR-based restriction fragment length polymorphism. In the healthy controls, frequencies of the CYP1A1 variant alleles for m1 (CYP1A1(*)2A) and the GSTM1null genotype were found to be 0.25 and 0.19, respectively. In the oral cancer patients, these frequencies were 0.33 and 0.50, respectively. Thus, the GSTM1 and m1 rare alleles were significantly more frequent in the oral cancer patients compared to the controls. The estimated relative risk for oral cancer associated with the single genotype CYP1A1 or GSTM1 was 2.08 for wt/m1, 1.04 fo...
Revista chilena de cardiología, 2011
Determinación del polimorismo de CYP2C9*2 y su relación con la farmacocinética de acenocumarol en... more Determinación del polimorismo de CYP2C9*2 y su relación con la farmacocinética de acenocumarol en voluntarios sanos.
Frontiers in Genetics, 2012
Cancer is a leading cause of death worldwide. The cancer incidence rate in Chile is 133.7/100,000... more Cancer is a leading cause of death worldwide. The cancer incidence rate in Chile is 133.7/100,000 inhabitants and it is the second cause of death, after cardiovascular diseases. Most of the antineoplastic drugs are metabolized to be detoxified, and some of them to be activated. Genetic polymorphisms of drug-metabolizing enzymes can induce deep changes in enzyme activity, leading to individual variability in drug efficacy and/or toxicity. The present research describes the presence of genetic polymorphisms in the Chilean population, which might be useful in public health programs for personalized treatment of cancer, and compares these frequencies with those reported for Asian and Caucasian populations, as a contribution to the evaluation of ethnic differences in the response to chemotherapy. We analyzed 23 polymorphisms in a group of 253 unrelated Chilean volunteers from the general population. The results showed that CYP2A6 * 2, CYP2A6 * 3, CYP2D6 * 3, CYP2C19 * 3, and CYP3A4 * 17 variant alleles are virtually absent in Chileans. CYP1A1 * 2A allele frequency (0.37) is similar to that of Caucasians and higher than that reported for Japanese people. Allele frequencies for CYP3A5 * 3(0.76) and CYP2C9 * 3(0.04) are similar to those observed in Japanese people. CYP1A1 * 2C(0.32), CYP1A2 * 1F (0.77), CYP3A4 * 1B(0.06), CYP2D6 * 2(0.41), and MTHFR T(0.52) allele frequencies are higher than the observed either in Caucasian or in Japanese populations. Conversely, CYP2C19 * 2 allelic frequency (0.12), and genotype frequencies for GSTT1 null (0.11) and GSTM1 null (0.36) are lower than those observed in both populations. Finally, allele frequencies for CYP2A6 * 4(0.04), CYP2C8 * 3(0.06), CYP2C9 * 2(0.06), CYP2D6 * 4(0.12), CYP2E1 * 5B(0.14), CYP2E1 * 6(0.19), and UGT2B7 * 2(0.40) are intermediate in relation to those described in Caucasian and in Japanese populations, as expected according to the ethnic origin of the Chilean population. In conclusion, our findings support the idea that ethnic variability must be considered in the pharmacogenomic assessment of cancer pharmacotherapy, especially in mixed populations and for drugs with a narrow safety range.
Physiological Reports, 2022
Acetylcholine (ACh) may be involved in the regulation of ovarian functions. A previous systemic s... more Acetylcholine (ACh) may be involved in the regulation of ovarian functions. A previous systemic study in rats showed that a 4-week, intrabursal local delivery of the ACh-esterase blocker Huperzine-A increased intraovarian ACh levels and changed ovarian follicular development, as evidenced by increased healthy antral follicle numbers and corpora lutea, as well as enhanced fertility. To further characterize the ovarian cholinergic system in the rat, we studied whether innervation may contribute to intraovarian ACh. We explored the cellular distribution of three muscarinic receptors (MRs; M1, M3, and M5), analyzed the involvement of MRs in ovarian steroidogenesis, and examined their roles in ovarian follicular development in normal conditions and in animals exposed to stressful conditions by employing the muscarinic antagonist, atropine. Denervation studies decreased ovarian norepinephrine, but ovarian ACh was not affected, evidencing a local, nonneuronal source of ACh. M1 was located on granulosa cells (GCs), especially in large antral follicles. M5 was associated with the ovarian vascular system and only traces of M3 were found. Ex vivo ovary organo-typic incubations showed that the MR agonist Carbachol did not modify steroid production or expression of steroid biosynthetic enzymes. Intrabursal, in vivo application of atropine (an MR antagonist) for 4 weeks, however, increased atresia of the secondary follicles. The results support the existence of an intraovarian cholinergic system in the rat ovary, located mainly in follicular GCs, which is not involved in steroid production but rather via MRs exerts trophic functions and regulates follicular atresia.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Journal of Natural Remedies, 2015
Encelia canescens Lam (nv: mancapaqi, mataloba, matalobo, mucle, or “coronilla de fraile”) is a 3... more Encelia canescens Lam (nv: mancapaqi, mataloba, matalobo, mucle, or “coronilla de fraile”) is a 30-80-cm high shrubby perennial plant that grows in the Atacama and Coquimbo regions of Chile up to 1,700 m above the sea. The present research was performed to examine the toxicological, antioxidant and antitumoural properties of aqueous and ethanol Encelia canescens Lam extracts. Our results revealed the presence of saponins, terpenes, flavonoids, coumarins and tannins. The total phenolic compound contents were 19±1.14 mg/g tannic acid in the aqueous extract and 23±1.60 mg/g tannic acid in the ethanol extract. The total flavonoid contents were 0.15±0.02 mg/g quercetinin the aqueous extract and 0.13±0.06 mg/g quercetinin the ethanol extract. Based on 2,2-diphenyl-1-picrylhydrazyl assays, the antioxidant capacities were 354±23 µmol trolox/100 g of the dry ethanol extract and 303±15 µmol trolox/100 g of the dry aqueous extract. Using 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulphonic ac...
Journal of Endocrinology
RFamide-related peptide (RFRP-3) is a regulator of GnRH secretion from the brain, but it can also... more RFamide-related peptide (RFRP-3) is a regulator of GnRH secretion from the brain, but it can also act in human ovary to influence steroidogenesis. We aimed to study the putative local role of RFRP-3 in the ovary and its potential participation in the development of a polycystic ovary phenotype induced by chronic sympathetic stress (cold stress). We used adult Sprague–Dawley rats divided into control and stressed groups. In both groups, we studied the effect of intraovarian exposure to RFRP-3 on follicular development and plasma ovarian steroid concentrations. We also tested the effect of RFRP-3 on ovarian steroid production in vitro. Chronic in vivo intraovarian exposure to RFRP-3 decreased basal testosterone concentrations and cold stress-induced progesterone production by the ovary. In vitro, RFRP-3 decreased hCG-induced ovarian progesterone and testosterone secretion. Immunohistochemistry and mRNA expression analysis showed a decrease in Rfrp and expression of its receptor in the...
Revista chilena de cardiología, 2011
Determinación del polimorfismo de CYP2C9*2 y su relación con la farmacocinética de acenocumarol e... more Determinación del polimorfismo de CYP2C9*2 y su relación con la farmacocinética de acenocumarol en voluntarios sanos.
Polycyclic aromatic hydrocarbons (PAHs) contained in tobacco smoke acquire carcinogenicity follow... more Polycyclic aromatic hydrocarbons (PAHs) contained in tobacco smoke acquire carcinogenicity following their activation by xenobiotic-metabolizing enzymes to highly reactive metabolites. The cytochrome P4501A1 (CYP1A1) enzyme is central to the metabolic activation of these PAHs, and GSTM1 is the main enzyme responsible for its detoxiication.
Cuadernos médicos-sociales
En Chile la incidencia de leucemia es de 4.2/100.000 adultos al año. Dentro de ellas, 2,8/100.000... more En Chile la incidencia de leucemia es de 4.2/100.000 adultos al año. Dentro de ellas, 2,8/100.000 son leucemias agudas y 1,4/100.000 son leucemias crónicas. La quimioterapia para el cáncer ha progresado desde su introducción a la práctica clínica y constituye una modalidad terapéutica muy útil en las leucemias. Sin embargo, su uso se ve limitado por la imposibilidad de predecir la respuesta individual, por lo que la elección de la terapia suele ser en base a criterios médicos y de las guías clínicas establecidas. Esta variación inter-individual en la respuesta a un fármaco antineoplásico puede deberse a factores farmacocinéticos y/o farmacodinámicos, relacionados con otros factores genético-metabólicos, que se traducen en variantes polimórficas de las enzimas encargadas de la biotransformación de estos fármacos o receptores. Al respecto, se estima que la genética da cuenta entre un 20 a un 95% de la variabilidad en la respuesta terapéutica y toxicológica. De todas las drogas conocid...
During the last years science and technology of molecular diagnostic in order to assay personaliz... more During the last years science and technology of molecular diagnostic in order to assay personalized drug response or suitability to a specific pharmacological treatment experienced a rapid development. Therefore, with this subject clinical laboratory has evolved in complex technologies. The advances in pharmacogenetics allow us to point out that variability is the rule and not the exception, in majority of the pharmacological treatments, thus it is essential to incorporate in clinical laboratories this scientific tool through reliable assays. The implementation of PCR and/or RT-PCR analyses is affordable and the cost is justified considering costs for medication adjustment of dose The investment for the implementation of a Laboratory of Molecular Analysis in clinical centers should consider a necessary surface which must include: DNA extraction area, PCR room and a results processing area, according international guidelines, basic infraestructure and qualified staff. Therefore, it i...
Oncology letters, 2010
Polycyclic aromatic hydrocarbons (PAHs) contained in tobacco smoke acquire carcinogenicity follow... more Polycyclic aromatic hydrocarbons (PAHs) contained in tobacco smoke acquire carcinogenicity following their activation by xenobiotic-metabolizing enzymes to highly reactive metabolites. The cytochrome P4501A1 (CYP1A1) enzyme is central to the metabolic activation of these PAHs, and GSTM1 is the main enzyme responsible for its detoxification. CYP1A1 and GSTM1 polymorphisms were evaluated in 124 Chilean healthy controls and 48 oral cancer patients through PCR-based restriction fragment length polymorphism. In the healthy controls, frequencies of the CYP1A1 variant alleles for m1 (CYP1A1(*)2A) and the GSTM1null genotype were found to be 0.25 and 0.19, respectively. In the oral cancer patients, these frequencies were 0.33 and 0.50, respectively. Thus, the GSTM1 and m1 rare alleles were significantly more frequent in the oral cancer patients compared to the controls. The estimated relative risk for oral cancer associated with the single genotype CYP1A1 or GSTM1 was 2.08 for wt/m1, 1.04 fo...
Revista chilena de cardiología, 2011
Determinación del polimorismo de CYP2C9*2 y su relación con la farmacocinética de acenocumarol en... more Determinación del polimorismo de CYP2C9*2 y su relación con la farmacocinética de acenocumarol en voluntarios sanos.
Frontiers in Genetics, 2012
Cancer is a leading cause of death worldwide. The cancer incidence rate in Chile is 133.7/100,000... more Cancer is a leading cause of death worldwide. The cancer incidence rate in Chile is 133.7/100,000 inhabitants and it is the second cause of death, after cardiovascular diseases. Most of the antineoplastic drugs are metabolized to be detoxified, and some of them to be activated. Genetic polymorphisms of drug-metabolizing enzymes can induce deep changes in enzyme activity, leading to individual variability in drug efficacy and/or toxicity. The present research describes the presence of genetic polymorphisms in the Chilean population, which might be useful in public health programs for personalized treatment of cancer, and compares these frequencies with those reported for Asian and Caucasian populations, as a contribution to the evaluation of ethnic differences in the response to chemotherapy. We analyzed 23 polymorphisms in a group of 253 unrelated Chilean volunteers from the general population. The results showed that CYP2A6 * 2, CYP2A6 * 3, CYP2D6 * 3, CYP2C19 * 3, and CYP3A4 * 17 variant alleles are virtually absent in Chileans. CYP1A1 * 2A allele frequency (0.37) is similar to that of Caucasians and higher than that reported for Japanese people. Allele frequencies for CYP3A5 * 3(0.76) and CYP2C9 * 3(0.04) are similar to those observed in Japanese people. CYP1A1 * 2C(0.32), CYP1A2 * 1F (0.77), CYP3A4 * 1B(0.06), CYP2D6 * 2(0.41), and MTHFR T(0.52) allele frequencies are higher than the observed either in Caucasian or in Japanese populations. Conversely, CYP2C19 * 2 allelic frequency (0.12), and genotype frequencies for GSTT1 null (0.11) and GSTM1 null (0.36) are lower than those observed in both populations. Finally, allele frequencies for CYP2A6 * 4(0.04), CYP2C8 * 3(0.06), CYP2C9 * 2(0.06), CYP2D6 * 4(0.12), CYP2E1 * 5B(0.14), CYP2E1 * 6(0.19), and UGT2B7 * 2(0.40) are intermediate in relation to those described in Caucasian and in Japanese populations, as expected according to the ethnic origin of the Chilean population. In conclusion, our findings support the idea that ethnic variability must be considered in the pharmacogenomic assessment of cancer pharmacotherapy, especially in mixed populations and for drugs with a narrow safety range.