Quercetin and resveratrol are associated with the downregulation of TNFalpha/NF-kB/inos axis-mediated acute liver injury in rats induced by paracetamol poisoning / La quercetina y el resveratrol están asociados con la regulación decreciente de la lesión hepática aguda mediada por el eje TNF-alfa/NF-kB/inos en ratas inducida por envenenamiento con paracetamol

SUMMARY: Paracetamol (known as acetaminophen, or APAP) poisoning causes acute liver damage that can lead to organ failure and death. We sought to determine that APAP overdose can augment tumor necrosis factor-alpha (TNF-α)/ nuclear factor kappa B (NF-kB)/induced nitic oxide synthase (iNOS) axis-mediated hepatotoxicity in rats, and the anti-inflammatory polyphenolic compounds, quercetin (QUR) plus resveratrol (RES) can ameliorate these parameters. Therefore, we induced acute hepatotoxicity in rats using APAP overdose (2 g/kg, orally) and the protective group of rats were treated with 50 mg/kg QUR plus 30 mg/kg RES for one week before APAP ingestion. Animals were killed at day 8. APAP poisoning caused the induction of hepatic tissue levels of TNF-α, NF-kB, and iNOS, which were significantly (p<0.05) decreased by QUR+RES. QUR+RES, also inhibited liver injury biomarkers, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Additionally, a link between liver injury and TNF-α /NF-kB / iNOS axis mediated hepatotoxicity was observed. Thus, the presented data backing the conclusion that intoxication by paracetamol increases TNF-α / NF-kB / iNOS axis -mediated hepatotoxicity, and is protected by a combination of quercetin and resveratrol.

El envenenamiento por paracetamol (conocido como acetaminofeno o APAP) causa daño hepático agudo que puede provocar una insuficiencia orgánica y la muerte. El objetivo de este trabajo fue determinar si la sobredosis de APAP puede aumentar la hepatotoxicidad mediada por el eje del factor de necrosis tumoral alfa (TNF-α)/factor nuclear kappa B (NF-kB)/óxido nítico sintasa inducida (iNOS) en ratas, y si el polifenólico antiinflamatorio compuesto por quercetina (QUR) más resveratrol (RES) pueden mejorar estos parámetros. Por lo tanto, inducimos hepatotoxicidad aguda en ratas usando una sobredosis de APAP (2 g/kg, por vía oral). El grupo protector de ratas se trató con 50 mg/ kg de QUR más 30 mg/kg de RES durante una semana antes de la ingestión de APAP. Los animales se sacrificaron el día 8. El envenenamiento con APAP en el tejido hepático provocó la inducción de niveles de TNF-α, NF-kB e iNOS, que se redujeron significativamente (p<0,05) con QUR+RES. QUR+RES, también inhibió los biomarcadores de daño hepático, la alanina aminotransferasa (ALT) y el aspartato aminotransferasa (AST). Además, se observó una relación entre la lesión hepática y la hepatotoxicidad mediada por el eje TNF-α /NF-kB/iNOS. Por lo tanto, los datos presentados respaldan la conclusión de que la intoxicación por paracetamol aumenta la hepatotoxicidad mediada por el eje TNF-α /NF-kB / iNOS, y está protegida por una combinación de quercetina y resveratrol.

Enhancement of Annexin V in response to combination of epigallocatechin gallate and quercetin as a potent arrest the cell cycle of colorectal cancer / Aumento da anexina V em resposta à combinação de galato de epigalocatequina e quercetina como uma potente parada do ciclo celular do câncer colorretal

Colorectal cancer (CRC) is one of the most common cancers leading to comorbidities and mortalities globally. The rational of current study was to evaluate the combined epigallocatechin gallate and quercetin as a potent antitumor agent as commentary agent for therapeutic protocol. The present study investigated the effect of epigallocatechin Gallate (EGCG) (150mg) and quercetin (200mg) at different proportions on proliferation and induction of apoptosis in human colon cancer cells (HCT-116). Cell growth, colonogenic, Annexin V in addition cell cycle were detected in response to phytomolecules. Data obtained showed that, the colony formation was inhibited significantly in CRC starting from the lowest concentration tested of 10 µg/mL resulting in no colonies as visualized by a phase-contrast microscope. Data showed a significant elevation in the annexin V at 100 µg/mL EGCG(25.85%) and 150 µg/mL quercetin (48.35%). Moreover, cell cycle analysis showed that this combination caused cell cycle arrest at the G1 phase at concentration of 100 µg/mL (72.7%) and 150 µg/mL (75.25%). The combined effect of epigallocatechin Gallate and quercetin exert antiproliferative activity against CRC, it is promising in alternative conventional chemotherapeutic agent.

O câncer colorretal (CCR) é um dos cânceres mais comuns, levando a comorbidades e mortalidade em todo o mundo. O racional do presente estudo foi avaliar a combinação de galato de epigalocatequina e quercetina como um agente antitumoral potente como agente de comentário para protocolo terapêutico. O presente estudo investigou o efeito de galato de epigalocatequina (EGCG) (150 mg) e quercetina (200 mg) em diferentes proporções na proliferação e indução de apoptose em células de câncer de cólon humano (HCT-116). O crescimento celular, colonogênico, anexina V, além do ciclo celular foram detectados em resposta a fitomoléculas. Os dados obtidos mostraram que a formação de colônias foi inibida significativamente no CRC a partir da concentração mais baixa testada de 10 µg/mL, resultando em nenhuma colônia conforme visualizado por um microscópio de contraste de fase. Os dados mostraram uma elevação significativa na anexina V a 100 µg/mL de EGCG (25,85%) e 150 µg/mL de quercetina (48,35%). Além disso, a análise do ciclo celular mostrou que essa combinação causou parada do ciclo celular na fase G1 na concentração de 100 µg/mL (72,7%) e 150 µg/mL (75,25%). O efeito combinado da epigalocatequina galato e quercetina exerce atividade antiproliferativa contra o CCR, é promissor como agente quimioterápico alternativo convencional.

Quercetin Inhibits ROS-p53-Bax-caspase-3 axis of apoptosis and augments gonadotropin and testicular hormones in chronic unpredictable stress-Induced testis injury / La quercetina inhibe el eje de apoptosis ROS-p53-Bax-caspasa-3 y aumenta la gonadotropina y las hormonas testiculares en la lesión testicular inducida por estrés crónico e impredecible

SUMMARY: A large body of evidence supports the protective role of the flavonol antioxidant compound quercetin in mammals. We tested the hypothesis that quercetin can protect against the hypothalamus-pituitary-gonadal (HPG) axis defect like a reduction in gonadotropins and testicular hormones and abnormal semen analysis induced by chronic unpredictable stress (CUS), possibly via the downregulation of oxidative stress (ROS) and p53-Bax-caspase-3 pathways. Rats were either exposed to a variety of unpredictable stressors daily before being sacrificed after 3 weeks (model group) or were treated with quercetin (50 mg/kg body weight/day) at the same time the CUS were induced (treated group). Harvested testicular tissues were stained with basic histological staining, and testis homogenates were assayed for the tumor suppressor p53, apoptosis regulator Bax, B-cell lymphoma 2 (Bcl-2), caspase-3, malondialdehyde (MDA), glutathione peroxidase (GPx), and superoxide dismutase (SOD). In addition, harvested epididymis tissues were used to assess semen analysis, and blood samples were assayed for the testicular hormone testosterone, the adrenal cortex hormone corticosterone, and the anterior pituitary gonadotropins, follicular stimulating hormone (FSH) and luteinizing hormone (LH). CUS induced profound testicular damage and significantly (p<0.05) induced p53, Bax, caspase-3, MDA, and corticosterone, which were significantly (p<0.05) inhibited by quercetin except corticosterone. Whereas, quercetin significantly (p<0.05) increased FSH, LH, testosterone, Bcl-2, GPx, and SOD levels that were inhibited by CUS. In addition, CUS induced oligozoospermia, asthenozoospermia, and teratozoospermia, which were significantly (p<0.05) protected by quercetin. Thus, Quercetin protects against CUS-induced HPG defects in rats, which is associated with the inhibition of ROS-p53-Bax-caspase-3 axis.

RESUMEN: El papel protector del compuesto antioxidante flavonol quercetina en los mamíferos ha sido ampliamente reportado. Probamos la hipótesis que la quercetina puede proteger contra el defecto del eje hipotálamo-hipofisiario- gonadal (HHG) como una reducción de gonadotropinas y hormonas testiculares y análisis de semen anormal inducido por estrés crónico impredecible (ECI), posiblemente a través de la regulación reducida del estrés oxidativo (REO) y las vías p53- Bax-caspasa-3. Las ratas fueron expuestas a una variedad de fac- tores estresantes impredecibles diariamente antes de ser sacrificadas después de 3 semanas (grupo modelo) o fueron tratadas con quercetina (50 mg / kg de peso corporal / día) al mismo tiempo que se indujo la ECI (grupo tratado). Los tejidos testiculares fueron teñidos con tinción histológica básica y los homogeneizados de testículo se analizaron para determinar el supresor de tumores p53, el regulador de apoptosis Bax, el linfoma de células B 2 (Bcl-2), la caspasa-3, el malondialdehído (MDA), la glutatión peroxidasa (GPx) y superóxido dismutasa (SOD). Además, se utilizaron tejidos del epidídimo recolectados para evaluar el análisis de semen y se analizaron muestras de sangre para determinar la hormona testicular testosterona, la hormona corticosterona de la corteza suprarrenal y las gonadotropinas de la hipófisis anterior, la hormona estimulante folicular (FSH) y la hormona luteinizante (LH). El ECI indujo daño testicular importante e indujo significativamente niveles de (p <0,05) p53, Bax, caspasa-3, MDA y corticosterona, que fueron inhibidos (p <0,05) por la quercetina. La quercetina aumentó significativamente (p <0,05) los niveles de FSH, LH, testosterona, Bcl-2, GPx y SOD que fueron inhibidos por ECI. Además, ECI indujo oligozoospermia, astenozoospermia y teratozoospermia, protegidos de manera significativa (p <0,05) por la quercetina. Por lo tanto, la quercetina protege contra los defectos de HHG inducidos por ECI en ratas, lo que está asociado con la inhibición del eje ROS-p53-Bax-caspasa-3.

Quercetin protects against acetaminophen-induced acute nephrotoxicity associated with the inhibition of biomarkers of acute kidney injury in rats / La quercetina protege contra la nefrotoxicidad aguda inducida por acetaminofén asociada con la inhibición de biomarcadores de lesión renal aguda en ratas

Acetaminophen (also called paracetamol, or APAP) causes acute kidney injury after accidental or intentional ingestion of a toxic dose of the drug. We tested whether the antioxidant and anti-inflammatory agent, quercetin (QUR) given alone can protect against acute nephrotoxicity induced by APAP overdose in a rat model of APAP-induced acute kidney injury. Rats were either given a single dose of APAP (2 g/kg) before being sacrificed after 24 hours or were pre-treated for 7 days with QUR (50 mg/kg) before being given a single dose of APAP and then sacrificed 24 hours post APAP ingestion. Kidneys were examined by light microscopy after staining with hematoxylin and eosin (H&E) and collected blood samples were assayed for biomarkers of oxidative stress, inflammation, and kidney injury. H&E stained sections of kidney from the model group of rats (APAP) showed substantial damage to the kidney architecture as demonstrated by widening of Bowman's space, tubular dilatation, vacuolization of tubular epithelium, and congested dilated blood vessels, which were partially protected by QUR. In addition, APAP significantly (p<0.05) increased blood levels of urea, creatinine, malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-a), and interleukin-6 (IL-6), which were significantly (p<0.05) reduced by QUR. These results indicate that quercetin partially protects against APAP-induced acute kidney injury in rats, which is associated with the inhibition of biomarkers of oxidative stress and inflammation and kidney injury.

El acetaminofeno (también llamado paracetamol o DCI) causa daño renal agudo después de la ingestión accidental o intencional de una dosis tóxica del medicamento. En el estudio analizamos si el agente antioxidante y antiinflamatorio, la quercetina (QUR) administrada sola, puede proteger contra la nefrotoxicidad aguda inducida por sobredosis de DCI en un modelo de rata. Las ratas recibieron una dosis única de DCI (2 g / kg) antes de ser sacrificadas después de 24 horas o fueron pretratadas durante 7 días con QUR (50 mg / kg) antes de recibir una dosis única de DCI y luego sacrificadas 24 horas post ingestión. Los riñones se examinaron mediante microscopía óptica después de la tinción con hematoxilina y eosina (H&E) y las muestras de sangre recolectadas se analizaron para detectar biomarcadores de estrés oxidativo, inflamación y daño renal. Las secciones de riñón teñidas con H&E del grupo modelo de ratas (DCI) mostraron un daño sustancial a la arquitectura del riñón, como lo demuestra la ampliación del espacio de Bowman, la dilatación tubular, la vacuolización del epitelio tubular y los vasos sanguíneos dilatados congestionados, que estaban parcialmente protegidos por QUR. Además, DCI aumentó significativamente (p <0,05) los niveles sanguíneos de la urea, creatinina, malondialdehído (MDA), factor de necrosis tumoral alfa (TNF-a) e interleucina-6 (IL-6), los que fueron reducidos significativamente (p < 0,05) por QUR. Estos resultados indican que la quercetina protege parcialmente contra la lesión renal aguda inducida por DCI en ratas, asociada con la inhibición de biomarcadores de estrés oxidativo, inflamación y lesión renal.

Acetaminophen induces alterations to the renal tubular ultrastructure in a rat model of acute nephrotoxicity protected by resveratrol and quercetin / El acetaminofeno induce alteraciones en la ultraestructura tubular renal en un modelo de rata con nefrotoxicidad aguda protegida por resveratrol y quercetina

Acetaminophen (also called paracetamol, or APAP) induced nephrotoxicity is reported after accidental or intentional ingestion of an overdose of the drug. Renal tubular ultrastructural alterations induced by APAP overdose associated with the induction of biomarkers of kidney injury have not been investigated before. Also, we investigated whether the combined polyphenolic anti-inflammatory and antioxidants agents, resveratrol (RES) and quercetin (QUR) can protect against APAP-induced acute kidney injury. The model group of rats received a single dose of APAP (2 g/kg), whereas the protective group of rats was pre-treated for 7 days with combined doses of RES (30 mg/kg) and QUR (50 mg/kg) before being given a single dose of APAP. All rats were then sacrificed one day post APAP ingestion. Harvested kidney tissues were prepared for transmission electron microscopy (TEM) staining and blood samples were assayed for urea, creatinine, and biomarkers of inflammation and oxidative stress. TEM images and blood chemistry analysis showed that APAP overdose induced kidney damage as demonstrated by substantial alterations to the proximal convoluted tubule ultrastructure, and a significant (p<0.05) increase in urea, creatinine, tumor necrosis factor-alpha (TNF-a), and malondialdehyde (MDA) blood levels, which were protected by RES+QUR. These findings indicate that APAP induces alterations to the renal tubular ultrastructure, which is inhibited by resveratrol plus quercetin, which also decreases blood levels of kidney injury biomarkers.

El objetivo de este trabajo fue estudiar la nefrotoxicidad inducida por acetaminofeno (también llamado paracetamol o APAP) después de la ingestión accidental o intencional de una sobredosis de la droga. Las alteraciones ultraestructurales tubulares renales inducidas por sobredosis de APAP asociadas con la inducción de biomarcadores de daño renal no se han investigado. Además, estudiamos si los agentes combinados antiinflamatorios y antioxidantes polifenólicos, el resveratrol (RES) y la quercetina (QUR) pueden proteger contra la lesión renal aguda inducida por APAP. El grupo modelo de ratas recibió una dosis única de APAP (2 g / kg), mientras que el grupo protector de ratas se trató previamente durante 7 días con dosis combinadas de RES (30 mg / kg) y QUR (50 mg / kg) antes de recibir una dosis única de APAP. Todas las ratas se sacrificaron un día después de la ingestión de APAP. Los tejidos renales fueron preparados para el análisis a través de la microscopía electrónica de transmisión (MET). En las muestras de sangre se determinaron la urea, creatinina y los biomarcadores de inflamación y estrés oxidativo. Las imágenes MET y el análisis químico de la sangre mostraron que la sobredosis de APAP inducía daño renal, como lo demuestran las alteraciones sustanciales en la ultraestructura del túbulo contorneado proximal, y además, de un aumento significativo (p <0,05) de la urea, creatinina, factor de necrosis tumoral alfa y niveles sanguíneos de malondialdehído, protegidos por RES + QUR. Estos hallazgos indican que APAP induce alteraciones en la ultraestructura tubular renal, inhibida por el resveratrol más quercetina, que también disminuye los niveles sanguíneos de biomarcadores de daño renal.

Suppression of hepatic apoptosis induced by acetaminophen using a combination of resveratrol and quercetin: an association of oxidative stress and interleukin-11 / Suspensión de la apoptosis hepática inducida por acetaminofén mediante una combinación de resveratrol y quercetina: una asociación de estrés oxidativo e interleucina-1

We sought to determine whether the combined polyphenolic compounds, resveratrol and quercetin can substantially protect against modulation of hepatic biomarkers of apoptosis and survival, p53-Bax axis and B-cell lymphoma 2 (Bcl-2) in an animal model of acetaminophen-induced acute liver injury via the association of oxidative stress and interleukin-11 (IL-11). The model group of rats received a single dose of acetaminophen (2 g/kg), whereas the protective group of rats was pre-treated for 7 days with combined doses of resveratrol (30 mg/kg) and quercetin (50 mg/kg) before being given a single dose of acetaminophen. All rats were then sacrificed 24 hours post acetaminophen ingestion. Acetaminophen overdose induced acute liver injury as demonstrated by profound liver parenchymal damage and increased levels of the liver injury enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Acetaminophen significantly (p<0.05) modulated malondialdehyde (MDA), p53, apoptosis regulator Bax, Bcl-2, IL-11, interleukin-6 (IL-6), ALT, AST, superoxide dismutase (SOD), and glutathione peroxidase (GPx), which were significantly protected by resveratrol plus quercetin. We further demonstrated a significant (p<0.01) correlation between IL-11 scoring and the levels of p53, Bax, Bcl-2, and MDA. Thus, resveratrol plus quercetin effectively protect against acetaminophen-induced apoptosis, which is associated with the inhibition of oxidative stress and IL-11.

En el estudio se intentó determinar si los compuestos polifenólicos combinados, el resveratrol y la quercetina pueden proteger sustancialmente contra la modulación de los biomarcadores hepáticos de apoptosis y supervivencia, el eje p53-Bax y el linfoma de células B 2 (Bcl-2) en un modelo animal de lesión hepática aguda inducida por acetaminofén, a través de la asociación del estrés oxidativo y la interleucina-11 (IL-11). El grupo modelo de ratas recibió una dosis única de acetaminofén (2 g / kg), mientras que el grupo protector de ratas fue tratado durante 7 días con dosis combinadas de resveratrol (30 mg / kg) y quercetina (50 mg / kg) antes de recibir una dosis única de acetaminofén. Todas los animales fueron sacrificados 24 horas después de la ingestión de acetaminofén. La sobredosis de acetaminofén indujo una lesión hepática aguda, como se observó en el daño profundo del parénquima hepático y el aumento de los niveles de las enzimas en la lesión hepática, alanina aminotransferasa (ALT) y aspartato aminotransferasa (AST). Acetaminofén moduló significativamente (p <0.05) malondialdehído (MDA), p53, regulador de apoptosis Bax, Bcl2, IL-11, interleucina-6 (IL-6), ALT, AST, superóxido dismutasa (SOD) y glutatión peroxidasa ( GPx), los que se encontraron significativamente protegidos por el resveratrol y quercetina. Además se determinó una correlación significativa (p <0.01) entre la puntuación de IL-11 y los niveles de p53, Bax, Bcl-2 y MDA. En conclusión, el resveratrol más la quercetina protegen de manera efectiva contra la apoptosis inducida por acetaminofén, asociada con la inhibición del estrés oxidativo y la IL-11.

A suplementação com quercetina previne mudanças em células imunorreativas à serotonina e caspase-3 do jejuno de ratos diabéticos / Quercetin supplementation prevents changes in the serotonin and caspase-3 immunoreactive cells of the jejunum of diabetic rats

ABSTRACT BACKGROUND: Serotonin (5-HT) is present in the epithelial enterochromaffin cells (EC), mast cells of the lamina propria and enteric neurons. The 5-HT is involved in regulating motility, secretion, gut sensation, immune system and inflammation. OBJECTIVE: Evaluate the effects of diabetes and quercetin supplementation on serotoninergic cells and its cell loss by apoptosis in jejunal mucosa of streptozotocin-induced diabetic rats (STZ-rats). METHODS: Twenty-four male Wistar rats were divided into four groups: normoglycemic (C), normoglycemic supplemented with 40 mg/day quercetin (Q), diabetic (D) and diabetic supplemented with 40 mg/day quercetin (DQ). After 120 days, the jejunum was collected and fixated in Zamboni's solution for 18 h. After obtaining cryosections, immunohistochemistry was performed to label 5-HT and caspase-3. Quantification of 5-HT and caspase-3 immunoreactive (IR) cells in the lamina propria, villi and crypts were performed. RESULTS: The diabetic condition displayed an increase of the number of 5-HT-IR cells in villi and crypts, while decreased number of these cells was observed in lamina propria in the jejunum of STZ-rats. In the diabetic animals, an increased density of apoptotic cells in epithelial villi and crypts of the jejunum was observed, whereas a decreased number of caspase-3-IR cells was observed in lamina propria. Possibly, quercetin supplementation slightly suppressed the apoptosis phenomena in the epithelial villi and crypts of the STZ-rats, however the opposite effect was observed on the 5-HT-IR cells of the lamina propria. Quercetin supplementation on healthy animals promoted few changes of serotoninergic function and apoptotic stimuli. CONCLUSION: These results suggest that quercetin supplementation mostly improved the serotonergic function affected by diabetes maybe due to antioxidant and anti-inflammatory properties of quercetin.

RESUMO CONTEXTO: A serotonina (5-HT) está presente nas células epiteliais enterocromafins (CE), nos mastócitos da lâmina própria e nos neurônios entéricos. A 5-HT está envolvida na regulação da motilidade, secreção, nocepção intestinal, sistema imunológico e inflamação. Objetivo: Avaliar os efeitos do diabetes e da suplementação de quercetina sobre a função serotoninérgica e a perda celular por apoptose na mucosa jejunal de ratos diabéticos induzidos por estreptozotocina (ratos STZ). MÉTODOS: Vinte e quatro ratos Wistar machos foram divididos em quatro grupos: normoglicêmico (C), normoglicêmico suplementado com quercetina 40 mg/dia (Q), diabético (D) e diabético suplementado com quercetina 40 mg/dia (DQ). Após 120 dias, o jejuno foi coletado e fixado na solução de Zamboni por 18 horas. Após a obtenção de cortes em criostato, a imuno-histoquímica foi realizada para marcar 5-HT e caspase-3. A quantificação de células imunorreativas (IR) à 5-HT e caspase-3 foram realizadas na lâmina própria, vilosidades e criptas. RESULTADOS: A condição diabética ocasionou um aumento do número de células 5-HT-IR nas vilosidades e criptas, enquanto que na lâmina própria houve uma redução dessas células, no jejuno de ratos STZ. Nos animais diabéticos, foi observada uma densidade aumentada de células apoptóticas no epitélio do jejuno, tanto nas vilosidades quanto nas criptas, por outro lado um número reduzido de células caspase-3-IR foi observado na lâmina própria. Possivelmente, a suplementação de quercetina suprimiu ligeiramente os fenômenos de apoptose no epitélio de vilosidades e criptas do jejuno de ratos STZ, no entanto, o efeito oposto foi observado nas células 5-HT-IR da lâmina própria. A suplementação com quercetina em animais saudáveis promoveu poucas alterações na função serotoninérgica e nos estímulos apoptóticos. CONCLUSÃO: Estes resultados sugerem que a suplementação de quercetina melhorou principalmente a função serotoninérgica afetada pelo diabetes, talvez devido às propriedades antioxidantes e anti-inflamatórias da quercetina.

Protective effect of quercetin on histomorphometric changes in kidney of retinoid acid-treated rat fetuses / Efecto protector de la quercetina sobre los cambios histomorfométricos en el riñón de fetos de rata tratados con ácido retinoico

SUMMARY: Retinoic acid, an active metabolite of vitamin A, plays essential signaling roles in mammalian embryogenesis. Prenatal rat fetuse exposure to retinoid induces some malformations in various organs, the most active and teratogenic metablolite is all-transretinoic acid (atRA). The teratogenic effects of some drugs can be prevented by the application of antioxidant drugs and stimulation of the maternal immune system. Also, quercetin, a naturally occurring flavonoid has excellent antioxidant properties. Therefore, the aim of this study was assess the protective effects of quercetin against atRA in fetuses of rat's kidney tissue. This study was performed on 40 pregnant rats that were divided into seven groups. Control group received normal saline and test groups received DMSO, quercetin (75 mg/kg), quercetin (200 mg/kg), atRA (25 mg/kg), atRA (25 mg/kg) plus quercetin (75 mg/kg) and atRA (25 mg/kg) plus quercetin (200 mg/kg), intraperitoneally at 8-10th days of gestation. Fetuses were collected at 20th day of gestation. Kidneys were collected and placed in 10 % buffered formalin solution. Then, kidneys were sectioned by routine method and stained by H&E and examined histologically. On histomorphomertrical examination, it was observed the priglomerular space and diameter of renal corpuscle in group which received only atRA were significantly (p≤0.05) greater than those received normal saline, dimethyl sulfoxide and quercetin, while these two indexes in group which received atRA plus quercetin significantly (p≤0.05) decreased by quercetin as dose dependent manner. Number of renal corpuscles were significantly (p≤0.05) decreased by atRA, but the quercetin could not affect the glomerular numbers. It is concluded that quercetin can protect fetuses against atRA damages and prevent their incidence probably via its antioxidant effect.

RESUMEN: El ácido retinoico, un metabolito activo de la vitamina A, desempeña un papel esencial de señalización en la embriogénesis de mamíferos. La exposición al ácido retinoico en fetos de ratas prenatales induce malformaciones en varios órganos, siendo el metabolito más activo y teratogénico el ácido transretinoico (ATRA). Los efectos teratogénicos de algunos medicamentos se pueden prevenir mediante la aplicación de medicamentos antioxidantes y la estimulación del sistema inmune materno. Además, la quercetina, un flavonoide de origen natural, tiene excelentes propiedades antioxidantes. Por lo tanto, el objetivo de este estudio fue evaluar los efectos protectores de quercetina contra ATRA en fetos de tejido de riñón de rata. Este estudio se realizó en 40 ratas preñadas que se dividieron en siete grupos. El grupo control recibió solución salina normal y los grupos de prueba recibieron DMSO, quercetina (75 mg / kg), quercetina (200 mg / kg), ATRA (25 mg / kg), ATRA (25 mg / kg) más quercetina (75 mg / kg) y ATRA (25 mg / kg) más quercetina (200 mg / kg), por vía intraperitoneal a los 8-10 días de gestación. Los fetos se recolectaron a los 20 días de gestación. Los riñones se recogieron y se colocaron en solución de formalina tamponada al 10 %. Luego, los riñones se seccionaron por método de rutina y se tiñeron con H & E y se examinaron histológicamente. En el examen histomorfométrico, se observó que el espacio periglomerular y el diámetro del corpúsculo renal en el grupo que recibió solo ATRA fueron significativamente (p≤0.05) mayores que los que recibieron solución salina normal, dimetilsulfóxido y quercetina, mientras que estos dos índices, en el grupo que recibió ATRA más quercetina, disminuyó significativamente (p≤0.05) en forma dependiente de la dosis. El número de corpúsculos renales disminuyó significativamente (p≤0.05) por el ATRA, pero la quercetina no pudo afectar el número de glomérulos. Se concluye que la quercetina puede proteger a los fetos contra daños de ATRA y prevenir su incidencia, probablemente, a través de su efecto antioxidante.

Quercetin inhibits chronic stress-induced myocardial infarction in rats / La quercetina inhibe el infarto al miocardio inducido por estrés crónico en ratas

RESUMEN: Reportamos recientemente que el estrés crónico súbito (ECS) induce disfunción ventricular izquierda (DVI) en ratas, la que fue inhibida por la quercetina un agente cardioprotector. En base de estos hallazgos y debido a que la mayoría de los pacientes con infarto de miocardio (IM) pueden desarrollar DVI e insuficiencia cardíaca, se buscó producir un modelo animal de IM y DVI en ratas, utilizando este modelo para probar la hipótesis de que la quercetina puede prevenir la inducción potencial de IM por ECS. Las ratas fueron expuestas a ECS usando una variedad de factores de estrés de quercetina (50 mg / kg de peso corporal / día) durante 21 días. Se registró la presión sanguínea y el electrocardiograma (ECG) en todos los grupos de ratas junto con el examen de homogeneizados de tejido del ventrículo izquierdo (VI) y secciones para confirmar la producción del modelo animal. Asociamos los recientes hallazgos sobre el papel de la apoptosis en la patología de DVI y, finalmente, IM. Las mediciones de la presión arterial y la grabación de ECG confirmaron el desarrollo de hipertensión sistémica y del IM en el grupo modelo de ratas expuestas a ECS. Además, la tinción histológica confirmó que el daño del VI se produjo en el mismo grupo. Tambien se obervó un aumento del gen proapoptótico Bax y de los biomarcadores inflamatorios, TNF-α e IL-6. El tratamiento simultáneo con quercetina redujo la presión sanguínea y evitó sustancialmente el IM, bloqueando el aumento del segmento ST en el ECG. Por lo tanto, el IM inducido por ECS en ratas asociado con el aumento de los biomarcadores de lesión tisular, fueron impedidos por la quercetina, lo que concuerda con nuestros hallazgos recientes de un posible papel terapéutico de la quercetina en la disfunción cardíaca inducida por ECS.

SUMMARY: We recently reported that chronic unpredictable stress (CUS) induced left ventricular dysfunction (LVD) in rats, which was inhibited by the cardioprotective agent quercetin. Based on these findings and because majority of patients with myocardial infarction (MI) can develop LVD and heart failure, we sought to produce an animal model of MI and LVD in rats and use this model to test the hypothesis that quercetin is able to prevent the potential MI induction by CUS. Rats were exposed to CUS using a variety of stressors in the presence and absence of quercetin (50 mg/kg body weight/day) for 21 days. Blood pressure and electrocardiogram (ECG) were recorded in all rat groups together with the examination of left ventricle (LV) tissue homogenates and sections to confirm the production of the animal model. We further extend on our recent findings on the role of apoptosis in the pathology of LVD and eventually MI. Blood pressure measurements and ECG recording confirmed the development of systemic hypertension and MI in the model group of rats exposed to CUS. In addition, histological staining confirmed that LV damages occurred in the same group. Furthermore, the proapoptotic gene Bax and the inflammatory biomarkers, TNF-α and IL-6 were augmented in LV homogenates by CUS. Simultaneous quercetin treatment lowered blood pressure and substantially prevented MI since it blocked the elevation of ST segment on the ECG and maintained a normal ECG reading. Quercetin suppressed the expression of Bax RNA messages, and significantly (p<0.05) blocked CUS-induced TNF-α and IL-6 upregulation. Thus, CUS induced MI in rats associated with augmentation of tissue injury biomarkers were prevented by quercetin, which further endorses our recent findings of a potential therapeutic role for quercetin in CUS induced cardiac dysfunction.

Quercetin inhibits left ventricular dysfunction induced by chronic stress in rats / La quercetina inhibe la disfunción ventricular izquierda inducida por el estrés crónico en ratas

Complications of chronic stress including cardiovascular disease are among the common public health problems that affect the lives of millions of people around the globe. We sought to determine whether the anti-oxidant and anti-apoptotic agent, quercetin can inhibit chronic stress-induced left ventricular dysfunction (LVD). Chronic unpredictable stress (CUS) was induced in rats using a variety of stressors in the presence and absence of quercetin (50 mg/kg body weight/day). Harvested tissues from the left ventricles (LV) of these animals were examined using basic histological staining. In addition, LV tissue homogenates were assayed for markers of oxidative and anti-oxidative stress that are known to be modulated in cardiac dysfunction. Furthermore, LV pressure was monitored by a pressure catheter inserted directly into the LV. Histopathological examinations of the LV in the model group (CUS) showed a profound damage to LV compared to the control group as demonstrated by a severe damage of cardiomyocytes and an increase of inflammatory cell infiltration, which was prevented by quercetin. CUS increased LV end-diastolic pressure that was significantly blocked by quercetin. In addition, quercetin significantly (p<0.05) blocked CUS-induced inhibition of the anti-oxidant superoxide dismutase (SOD) and the survival Bcl-2 proteins. Quercetin also significantly (p<0.05) inhibited CUS-induced augmentation of the oxidative stress TBARS and the apoptotic protein caspase-3. We conclude that LVD induced by CUS possibly via activation of oxidative and apoptosis pathways can be inhibited by quercetin; thus may offer therapeutic potential in humans.

Las complicaciones del estrés crónico, incluyendo las enfermedades cardiovasculares, se encuentran entre los problemas comunes de salud pública que afectan la vida de millones de personas en todo el mundo. En este trabajo se buscó determinar si la quercetina, agente antioxidante y antiapoptótico, puede inhibir la disfunción ventricular izquierda (DVI) inducida por estrés crónico. Se indujo estrés crónico impredecible (ECI) en ratas utilizando una variedad de factores de estrés, en presencia y ausencia de quercetina (50 mg / kg de peso corporal / día). Las muestras recolectadas de los ventrículos izquierdos (VI) de estos animales se examinaron usando tinción histológica básica. Además, los homogenados de tejido de VI se utilizaron para detectar marcadores de estrés oxidativo y anti-oxidativo que se conocen están modulados en la disfunción cardíaca. Además, la presión del VI se controló mediante un catéter de presión insertado directamente en el VI. Los exámenes histopatológicos del VI en el grupo modelo (ECI) mostraron un daño profundo al VI en comparación con el grupo control, como lo demuestra un grave daño de los cardiomiocitos y un aumento de la infiltración de células inflamatorias, que fue evitado por la quercetina. El ECI aumentó la presión diastólica final del VI, que fue bloqueada significativamente por la quercetina. Además, la quercetina bloqueó en forma significativa (p <0,05) el ECI inducida por la inhibición de la antioxidante superóxido dismutasa (SOD) y la supervivencia de proteínas Bcl-2. Quercetina también inhibió en forma significativa (p <0,05) el ECI inducido por el aumento de la tensión oxidativa y la proteína apoptótica caspasa-3. Llegamos a la conclusión de que la DVI inducida por ECI, posiblemente a través de la activación de las vía oxidativa y la apoptosis, pueden ser inhibidos por la quercetina, pudiendose ofrecer entonces como un potencial terapéutico en los seres humanos.

Effects of quercetin-supplementation in NADH-diaphorase positive neurons subpopulations in the ileum of rats with experimental diabetes mellitus / Efectos de la suplementación con quercetina en subpoblaciones de neuronas NADH-diaforasa positivas en el Ileon de ratas con diabetes mellitus experimental

The effects of quercetin supplementation in NADH-diaphorase positive (NADH-d) neurons of streptozotocin-induced diabetic rats was carried in this study. Fifteen male rats were divided into three groups: normoglycemic (N), diabetic (D) and diabetic supplemented with quercetin (DQ). Whole mount preparations of the muscular layer of the ileum underwent NADH-d histochemistry for evidencing the NADH-d neuronal subpopulation. Quantitative analyzes were performed on 30 random fields, and morphometric analyzes in 100 neuronal bodies and nuclei per animal. The supplementation promoted a 44 % reduction in the neuronal density in D group when compared to N group (p <0.001); a 24.5 % reduction was observed in the DQ group when compared to N (p <0.01). Animals in D group presented an 18.7 % increase in the cell body areas of myenteric neurons when compared to N (p <0.001); DQ group showed a 14.2 % decrease in neuronal areas when compared to D (p <0.01); the nuclear area were similar among the three groups. We conclude that quercetin supplementation was positive for animals with diabetes mellitus.

Se estudiaron los efectos de la suplementación con quercetina en neuronas NADH-diaforasa positiva (NADH-d) de ratas diabéticas inducidas por estreptozotocina. Quince ratas machos se dividieron en tres grupos: normoglicémico (N), diabéticos (D) y diabéticos suplementados con quercetina (DQ). Las cortes montados de la capa muscular del íleon fueron sometidos a histoquímica de NADH-d para evidenciar la subpoblación neuronal NADH-d. Se realizaron análisis cuantitativos en 30 campos aleatorios y análisis morfométricos en 100 cuerpos y núcleos neuronales, por animal. La suplementación promovió una reducción del 44 % en la densidad neuronal en el grupo D cuando se comparó con el grupo N (p <0,001). Se observó una reducción del 24,5 % en el grupo DQ en comparación con N (p <0,01). Los animales del grupo D presentaron un aumento del 18,7 % en las áreas del cuerpo celular de las neuronas mientéricas cuando se compararon con N (p <0,001). El grupo DQ mostró una disminución de 14,2 % en las áreas neuronales en comparación con D (p <0,01). El área nuclear fue similar entre los tres grupos. Se concluye que la suplementación con quercetina fue positiva para animales con diabetes mellitus.

Quercetin and β-sitosterol prevent high fat diet induced dyslipidemia and hepatotoxicity in Swiss albino mice.

High fat diet group showed a significant rise in serum and hepatic total cholesterol, triglyceride and atherogenic index which are major biomarkers of dyslipidemia and cardiovascular risk. The liver function markers, lipid peroxidation and proinflammatory cytokine levels were elevated in high fat diet group whereas antioxidant levels significantly reduced. These findings manifest hepatic damage which was further confirmed by histological findings. Quercetin and β-sitosterol though structurally different yet both ameliorate the sickening changes in different mechanism. The current investigation is perhaps the first report of the mechanistic role of two polyphenols over dyslipidemia and subsequent hepatotoxicity.

Compuestos bioactivos e inflamaciónligada a obesidad / Bioactive compounds and inflammation linked to obesity

Obesity has emerged among the major worldwide health threats. This pathology is characterized by the presence of a chronic inflammatory state in the overgrowing adipose tissue. This state has been related with an increased monocyte infiltration, and consequently with an establishment of an adipocyte-macrophage interaction, which in turn has been linked with the onset of obesity-related insulin resistance. Consequently, reducing this pathogenic crosstalk could comprise an interesting approach to counteract this inflammation. In this context, the screening of natural compounds with known anti-inflammatory/antioxidant properties over this crosstalk could be of highly significance. Popular culture and some investigations have point out that foods richs in polyphenols and essential fatty acids are known to possess these characteristics. It has been described that isolated bioactive compounds presents promising beneficial properties against the expression or secretion of inflammatory markers that are induced by the adipocyte-macrophage communication. Therefore, the proper evaluation of these compounds or the identification of new ones with potential characteristics is actually needed in aiming to reduce the increasing tendency of obesity-related pathologies, such as type 2 diabetes...

Quercetin improves the in vitro development of porcine oocytes by decreasing reactive oxygen species levels

Quercetin is a plant-derived flavonoid found in fruits or vegetables that has antioxidant properties and acts as a free radical scavenger. We investigated the effects of quercetin on porcine oocyte nuclear maturation and embryonic development after parthenogenetic activation. We then evaluated the antioxidant activities of quercetin by measuring reactive oxygen species (ROS) levels in matured oocytes. Immature oocytes were untreated or treated with 1, 10, and 50 microg/mL quercetin during in vitro maturation (IVM). Quercetin treatment did not improve oocyte nuclear maturation, but significantly higher blastocyst rates (p < 0.05) of parthenogenetically activated oocytes were achieved when the IVM medium was supplemented with an adequate concentration of quercetin (1 microg/mL). However, cleavage rates and blastocyst cell numbers were not affected. Oocytes treated with 1 or 10 microg/mL quercetin had significantly lower (p < 0.05) levels of ROS than the control and group treated with the highest concentration of quercetin (50 microg/mL). Moreover, this highest concentration was detrimental to oocyte nuclear maturation and blastocyst formation. Based on our findings, we concluded that exogenous quercetin reduces ROS levels during oocyte maturation and is beneficial for subsequent embryo development.

Quercetin improves the in vitro development of porcine oocytes by decreasing reactive oxygen species levels

Quercetin is a plant-derived flavonoid found in fruits or vegetables that has antioxidant properties and acts as a free radical scavenger. We investigated the effects of quercetin on porcine oocyte nuclear maturation and embryonic development after parthenogenetic activation. We then evaluated the antioxidant activities of quercetin by measuring reactive oxygen species (ROS) levels in matured oocytes. Immature oocytes were untreated or treated with 1, 10, and 50 microg/mL quercetin during in vitro maturation (IVM). Quercetin treatment did not improve oocyte nuclear maturation, but significantly higher blastocyst rates (p < 0.05) of parthenogenetically activated oocytes were achieved when the IVM medium was supplemented with an adequate concentration of quercetin (1 microg/mL). However, cleavage rates and blastocyst cell numbers were not affected. Oocytes treated with 1 or 10 microg/mL quercetin had significantly lower (p < 0.05) levels of ROS than the control and group treated with the highest concentration of quercetin (50 microg/mL). Moreover, this highest concentration was detrimental to oocyte nuclear maturation and blastocyst formation. Based on our findings, we concluded that exogenous quercetin reduces ROS levels during oocyte maturation and is beneficial for subsequent embryo development.

Novedades Científicas / Scientific novelty

La medicina complementaria y alternativa (MCA) se utiliza, en más de 80% de la población mundial y se esta convirtiendo en un componente en acceso para el sistema de salud de EE.UU. La información sobre las terapias de MCA; representa cada vez más un desafio para los médicos, porque casi el 40% de sus pacientes pueden utilizarla y otro 50% considerar su adquisición, como parte de un régimen alterno, en el cuidado de su salud. La población que utiliza al menos una véz la MCA es de un 70% de la población y el gasto anual alcanza unos $ 34 mil millones. El Informe Nacional sobre Estadísticas de Salud para el año 2007 describe, que el método terapéutico de mayor uso se basó en productos de tipo naturales hasta un 17,7%, sin incluir vitaminas o minerales. Más del 5% de los niños menores de 18 años de edad utilizaron la MCA para condiciones alérgicas como el asma. La cantidad y calidad de ls información disponible y la preocupación acerca de la responsabilidad de su riesgo, representan un reto para la mayoría de los médicos en cualquier país. Desde la creación del Centro Nacional para la Medicina Complementaria y Alternativa se ha producido un enorme aumento en el número de ensayos clínicos en ciencias básicas y terapéuticas basada en la exploración de la MCA. La inmunología clínica, en particular la subespecialidad de enfermedades alérgicas, representa un área fértil por el gran número de terapias MCA que han demostrado afectar el sistema inmune. Recientemente, se han descubierto los posibles mecanismos bioquímicos involucrados en la vía de los inmunomoduladores, suplementos de vitaminas (A, D y E), que parecen afectar la diferenciación de células CD4 y sus subclases Th1 y Th2. Otras investigaciones han demostrado que las hiervas tales como el resveratrol, quercetina y magnolol pueden actuar a nivel de los factores de transcripción como el nuclear-kB y en la señal del transductor y activadose de las vías de transcripción/Janus kinasa

Efeitos da quercetina na lesão pulmonar induzida por bleomicina: um estudo preliminar / Effects of quercetin on bleomycin-induced lung injury: a preliminary study

OBJETIVO: Investigar os efeitos da quercetina em um modelo de inflamação pulmonar e fibrose induzidas por bleomicina. MÉTODOS: Setenta e nove hamsters machos adultos foram randomizados para aplicação de injeções pelas vias intratraqueal (IT) e intraperitoneal (IP) em quatro configurações: veículo IP/salina IT (grupo VS, n = 16); salina IT/quercetina IP (grupo QS, n = 16); bleomicina IT/veículo IP (grupo VB, n = 27); e bleomicina IT/quercetina IP (grupo QB, n = 20). A quercetina e a bleomicina foram aplicadas em doses de 30 mg/kg/dia e 10 U/kg, respectivamente.A quercetina foi iniciada/suspensa 3 dias antes/14 dias depois das injeções IT. RESULTADOS: A taxa de mortalidade do grupo VB foi significantemente superior à dos demais grupos (44 por cento vs. VS: 0 por cento; QS: 0 por cento; QB: 15 por cento). O grupo VB exibiu níveis pulmonares de substâncias reativas ao ácido tiobarbitúrico (× 10-2 nmol/mg) significativamente maiores (6,6 ± 1,3 vs. VS: 5,5 ± 0,8; QS: 2,5 ± 0,6; e QB: 5,8 ± 0,6).Os grupos VB/QB mostraram níveis pulmonares de glutationa reduzida (× 10-2 nmol/mg) significativamente menores que os dos grupos VS/QS (28,9 ± 13,8/28,6 ± 14,8 vs. 43,9 ± 16,0/51,1 ± 20,3) e níveis de hidroxiprolina (mg/g) significativamente maiores (201,6 ± 37,3/177,6 ± 20,3 vs. 109,6 ± 26,1/117,5 ± 32,0). CONCLUSÕES: Em um modelo animal de lesão pulmonar, a quercetina exibiu efeitos antiinflamatórios que são relacionados, pelo menos em parte, a suas propriedades antioxidantes.

OBJECTIVE: The aim of this study was to identify the best experimental model in which to observe the pulmonary alterations characterizing hepatopulmonary syndrome (HPS). METHODS: Male Wistar rats, with mean weight of 250 g, were used in four experimental models: inhaled carbon tetrachloride; intraperitoneal carbon tetrachloride; partial portal vein ligation; and bile duct ligation (BDL). The animals in all groups were divided into control and experimental subgroups. The following variables were measured: transaminase levels; blood gases; lipoperoxidation, using thiobarbituric acid reactive substances (TBARS) and chemiluminescence; and levels of superoxide dismutase (SOD) anti-oxidant activity. Anatomopathological examination of the lung was also performed. RESULTS: There were statistically significant differences between the BDL control and BDL experimental groups: aspartate aminotransferase (105.3 ± 43 vs. 500.5 ± 90.3 IU/L); alanine aminotransferase (78.75 ± 37.7 vs. 162.75 ± 35.4 IU/L); alkaline phosphatase (160 ± 20.45 vs. 373.25 ± 45.44 IU/L); arterial oxygen tension (85.25 ± 8.1 vs. 49.9 ± 22.5 mmHg); and oxygen saturation (95 ± 0.7 vs. 73.3 ± 12.07 percent). Lipoperoxidation and antioxidant activity also differed significantly between the two BDL groups (control vs. experimental): TBARS (0.87 ± 0.3 vs. 2.01 ± 0.9 nmol/mg protein); chemiluminescence (16008.41 ± 1171.45 vs. 20250.36 ± 827.82 cps/mg protein); and SOD (6.66 ± 1.34 vs. 16.06 ± 2.67 IU/mg protein). The anatomopathological examination confirmed pulmonary vasodilatation in the BDL model. In the other models, there were no alterations that were characteristic of HPS. CONCLUSIONS: The data obtained suggest that the BDL model can be used in future studies involving hepatic alterations related to oxidative stress and HPS.

Synergism of flavonoids with bacteriostatic action against Staphylococcus aureus ATCC 25 923 and Escherichia coli ATCC 25 922

In our previous studies, bacteriostatic action of flavonoids against Staphylococcus aureus ATCC 25 923 and Escherichia coli ATCC 25 922 was demostrated. In the present work synergism of their combinations in order to improve the bacteriostatic action against the same microorganisms was determined. The experiences were made in nutritive broth, maintaining constant one drug concentration (20 µg/ml) and increasing the other one. A turbidimetric kinetic method was used and by means of a mechanism previously proposed, the minimal inhibitory concentrations (MIC's) of each flavonoid combination were determined. The MIC's for assayed combinations against S. aureus were: variable morin - constant rutin: 157.44 µg/ml and variable quercetin - constant morin: 29.9 µg/ml. The values obtained against E. coli were: variable morin - constant rutin: 78.5 µg/ml; variable quercetin -constant rutin: 47.4 µg/ml; variable quercetin - constant morin: 25 µg/ml; variable morin - constant quercetin: 27.4 µg/ml.

Efficacies of plant phenolic compounds on sodium butyrate induced anti-tumour activity.

The ability of the differentiation inducing agent sodium butyrate (NaB) alone or combined with plant-derived phenolic compounds to produce growth inhibition in human erythroleukemic cells was investigated. As a single agent, curcumin produced a marked inhibition of proliferation indicated by its low concentration used. The effect of phenolics on the cell cycle could probably contribute to the augmented antiproliferative activity of NaB. The present data show that quercetin produced synergistic effect in terms of cell killing in association with NaB. Both curcumin and ferulic acid potentiated NaB-induced reduction of cell number. When NaB was added before exposure to graded doses of quercetin it did induce a greater inhibitory effect. The combination of NaB and quercetin seems less effective on S180 ascites tumour cells. As a single agent quercetin was found to be the most efficacious on S180 tumour model.

Efeitos das associaçöes de morina-ácido nicotínico e quercetina-ácido nicotínico no controle de lipídeos / Effects of the associations of morin-nicotinic acid and quercetin-nicotinic acid in the lipidic control

A aterosclerose pode ser considerada uma doença na circulaçäo coronariana. O presente trabalho estuda a açÄo da quercetina, morina, ácido nicotínico de maneira isolada e em associaçÄo envolvendo quercetina + ácido nicotínico e morina + ácido nicotínico no metabolismo lipídico. Foram dosados colesterol, colesterol-HDL e triacilglicerol após administraçäo de duas doses dos compostos morina, quercetina, morina + ácido nicotínico e quercetina + ácido nicotínico sendo a primeira imediatamente após a administraçäo do triton e a segunda dose, vinte horas depois. Decorridos quarenta e três horas após a administraçäo do triton o sangue foi analisado. Os resultados mostraram que morina + ácido nicotínico e quercetina + ácido nicotínico apresentaram os melhores resultados para colesterol (-83,77 porcento e 74,42 porcento). Para colesterol-HDL os melhores resultados foram com morina e com associaçäo quercetina + ácido nicotínico (+17,99 porcento e +21,96 porcento). Morina + ácido nicotínico mostraram os melhores níveis para triacilgliceróis (-83,77 porcento)