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1.
Am J Physiol Regul Integr Comp Physiol ; 324(2): R171-R182, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36503254

RESUMO

A high-fat (HF) diet causes fatty liver, hyperlipidemia, and hypercholesterolemia, and cottonseed oil (CSO) has been shown to improve liver and plasma lipids in human and mouse models. The purpose of this study was to determine the effect of CSO vs. olive oil (OO)-enriched diets on lipid levels in a HF-diet model of fatty liver disease. We placed mice on a HF diet to induce obesity and fatty liver, after which mice were placed on CSO or OO diets, with chow and HF (5.1 kcal/g) groups as control. When CSO- and OO-fed mice were given isocaloric diets with the HF group, there were no differences in body weight, plasma, or hepatic lipids. However, when the CSO and OO diets were reduced in calories (4.0 kcal/g), CSO and OO groups reduced body weight. The CSO group had lower plasma total cholesterol (-56 ± 6%, P < 0.01), free cholesterol (-53 ± 7%, P < 0.01), triglycerides (-61 ± 14%, P < 0.01), and LDL (-42 ± 16%, P = 0.01) vs. HF group whereas the OO diet lowered LDL (-18 ± 12%, P = 0.05) vs. HF. Furthermore, the CSO diet decreased hepatic total cholesterol (-40 ± 12%, P < 0.01), free cholesterol (-23 ± 11%, P = 0.04), and triglycerides (-47 ± 12%, P = 0.02). There were no significant changes in lipogenesis and fatty acid oxidation among the groups. However, the CSO group increased lipid oxidative gene expression in liver and dihydrosterculic acid increased PPARα target genes with in vitro models. Taken together, consuming a reduced calorie diet enriched in CSO reduces liver and plasma lipid profiles in an obese model of fatty liver.


Assuntos
Óleo de Sementes de Algodão , Hepatopatia Gordurosa não Alcoólica , Animais , Masculino , Camundongos , Peso Corporal , Colesterol , Óleo de Sementes de Algodão/metabolismo , Óleo de Sementes de Algodão/farmacologia , Dieta Hiperlipídica , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Azeite de Oliva/farmacologia , Azeite de Oliva/metabolismo , Triglicerídeos
2.
J Sci Food Agric ; 102(13): 6169-6174, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35808803

RESUMO

BACKGROUND: Cottonseed oil is one of the most widely consumed cooking oils because of its high nutritional benefits and relatively low price. The present study evaluated the effects of tetramethoxy gossypol (TMG), a rarely reported degradation product of free gossypol produced in crudely extracted cottonseed oil, on the metabolic responses of liver, heart, spleen, kidney and lung tissues in rats using proton nuclear magnetic resonance (1 H NMR) spectroscopy combined with chemometric and bioinformatics techniques. RESULTS: Endogenous low-molecular-weight metabolites in rat liver, heart, spleen, kidney and lung tissues were profiled by 1 H NMR spectroscopy. The unsupervised principal components analysis and the supervised orthogonal partial least squares discriminant analysis revealed that the metabolic profiles in liver samples were greatly changed after TMG administration. Twenty significantly changed liver metabolites were screened out and further evaluated by receiver operating characteristic curve analysis, which were closely related to amino acid, glutathione, energy and lipid metabolism. CONCLUSION: Concerning the potential chronic exposure to TMG in cottonseed oil and other cottonseed products, the cumulative effects of dietary TMG on tissues, especially the liver, should be noted when improving the quality control standard of cottonseed oil. © 2022 Society of Chemical Industry.


Assuntos
Óleo de Sementes de Algodão , Gossipol , Animais , Óleo de Sementes de Algodão/análise , Óleo de Sementes de Algodão/química , Óleo de Sementes de Algodão/farmacologia , Dieta , Gossipol/análise , Gossipol/química , Gossipol/farmacologia , Fígado , Espectroscopia de Ressonância Magnética , Ratos
3.
J Nutr ; 152(9): 2060-2071, 2022 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-35511204

RESUMO

BACKGROUND: Increasing unsaturated fat intake is beneficial for cardiovascular health, but the type of unsaturated fat to recommend remains equivocal. OBJECTIVES: We investigated the effects of an 8-week diet intervention that was rich in either cottonseed oil (CSO; PUFA rich) or olive oil (OO; MUFA rich) on blood lipids in hypercholesterolemic adults. METHODS: Forty-three men and women with hypercholesterolemia (53 ± 10 years; BMI, 27.6 ± 4.8 kg/m2) completed this randomized parallel clinical trial consisting of an 8-week partial outpatient feeding intervention. Participants were given meals and snacks accounting for ∼60% of their daily energy needs, with 30% of energy needs from either CSO (n = 21) or OO (n = 22). At pre- and postdiet intervention visits, participants consumed a high-SFA meal (35% of total energy needs; 70% of energy from fat). The primary outcomes of fasting cholesterol profiles and secondary outcomes of postprandial blood lipids and glycemic markers were assessed over a 5-hour period. RESULTS: There were greater reductions from baseline to week 8 in fasting serum total cholesterol (TC; -17.0 ± 3.94 mg/dL compared with -2.18 ± 3.72 mg/dL, respectively; P = 0.008), LDL cholesterol (-19.7 ± 3.94 mg/dL compared with -5.72 ± 4.23 mg/dL, respectively; P = 0.018), non-HDL cholesterol (-20.8 mg/dL ± 4.00 compared with -6.61 ± 4.01 mg/dL, respectively; P = 0.014), and apoB (-11.8 mg/dL ± 2.37 compared with -3.10 ± 2.99 mg/dL, respectively; P = 0.05), in CSO compared with OO. There were also visit effects from baseline to week 8 for increases in HDL cholesterol (CSO, 56.5 ± 2.79 mg/dL to 60.2 ± 3.35 mg/dL, respectively; OO: 59.7 ± 2.63 mg/dL to 64.1 ± 2.24 mg/dL, respectively; P < 0.001), and decreases in the TC:HDL-cholesterol ratio (CSO, 4.30 ± 0.27 mg/dL to 3.78 ± 0.27 mg/dL, respectively; OO, 3.94 ± 0.16 mg/dL to 3.57 ± 0.11 mg/dL, respectively; P < 0.001), regardless of group assignment. In response to the high-SFA meal, there were differences in postprandial plasma glucose (P = 0.003) and triglyceride (P = 0.004) responses and a trend in nonesterified fatty acids (P = 0.11) between groups, showing protection in the postprandial state from an occasional high-SFA fat meal with CSO, but not OO, diet enrichment. CONCLUSIONS: CSO, but not OO, diet enrichment caused substantial improvements in fasting and postprandial blood lipids and postprandial glycemia in hypercholesterolemic adults. This trial was registered at clinicaltrials.gov as NCT04397055.


Assuntos
Hipercolesterolemia , Adulto , Glicemia , Colesterol , HDL-Colesterol , Óleo de Sementes de Algodão/farmacologia , Estudos Cross-Over , Dieta , Feminino , Humanos , Lipídeos , Masculino , Azeite de Oliva/farmacologia , Triglicerídeos
4.
Mol Neurobiol ; 58(6): 2494-2507, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33443681

RESUMO

Oxidative stress is believed to be one of the primary causes in ischemic stroke injury, and the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway is the most important endogenous antioxidative stress damage pathway. Cottonseed oil (CSO), which is used mostly as a solvent for lipid-soluble drugs, has been shown to exert antioxidative effects against peripheral tissue injury. However, the effects and mechanisms of CSO on ischemic stroke-induced oxidative stress injury and the Nrf2 signaling pathway remain largely unknown. In this study, we investigated the potential of CSO in regulating oxidative stress injury induced by middle cerebral artery occlusion and reperfusion (MCAO-R), or oxygen and glucose deprivation and reperfusion (OGD-R). We found that 1.3 mL/kg CSO treatment of male rats with a subcutaneous injection once every other day for 3 weeks significantly improved neurological deficit; reduced infarction volume; alleviated neuronal injuries; reduced the content of ROS and MDA; increased the activity of SOD, GSH, and GSH-PX; and markedly increased the expression of Nrf2. Furthermore, treatment with 10-9 µL/mL CSO to a neuron cell line (HT-22) for 24 h significantly increased cell viability and decreased cell apoptosis after OGD-R injury; significantly reduced the levels of ROS and MDA; increased the activity of SOD, GSH, and GSH-PX; and induced an increase in Nrf2 nuclear translocation. Based on our findings, we conclude that CSO treatment alleviates ischemic stroke injury-induced oxidative stress via activating the Nrf2 signaling pathway, highlighting the potential that CSO has as a therapeutic for ischemic strokes.


Assuntos
Óleo de Sementes de Algodão/uso terapêutico , AVC Isquêmico/tratamento farmacológico , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Transdução de Sinais , Animais , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Óleo de Sementes de Algodão/farmacologia , Glucose/deficiência , Masculino , Camundongos , Neurônios/efeitos dos fármacos , Neurônios/patologia , Estresse Oxidativo/efeitos dos fármacos , Oxigênio , Transporte Proteico/efeitos dos fármacos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/patologia
5.
J Neuroinflammation ; 17(1): 270, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32917229

RESUMO

BACKGROUND: Ischemic stroke is the second leading cause of death globally. The narrow time window for administering effective thrombolytic therapy motivates the search for alternative prevention strategies. Microglia and astrocyte activation-mediated inflammation play a pivotal role in ischemic stroke injury. Cottonseed oil (CSO) has been shown to exert anti-inflammatory effects against peripheral tissue injury, although CSO is mostly used as a solvent for lipid-soluble drugs. However, the role of CSO in neuroprotection against stroke has not been previously reported. METHODS: We treated adult male rats with CSO (1.3 ml/kg, subcutaneous injection, once every other day for 3 weeks) and then constructed a middle cerebral artery occlusion (MCAO) model followed by 24 h of reperfusion. Then, we measured the neurological scores, infarction volume, neuronal injury, and brain edema; we also measured the levels of pro-inflammatory cytokines (IL-1ß, IL-6, TNF-α), degree of microglial and astrocytic activation, protein expression levels of Toll-like receptor 4 (TLR4), nuclear factor kappa B (NF-κB), C3d and S100A10, and the presence of A1 type astrocytes and A2 type astrocytes. RESULTS: We found that CSO treatment significantly improved the neurological deficit, reduced infarction volume, and alleviated neuronal injuries, blood-brain barrier (BBB) disruption, and brain edema. Additionally, CSO treatment significantly reduced microglial and astrocytic activation, inhibited TLR4 and NF-κB protein expression, and reduced the release of IL-1ß, IL-6, and TNF-α. Finally, CSO treatment significantly decreased the number of C3d/glial fibrillary acidic protein (GFAP)-positive cells and C3d protein expression, and increased the number of S100A10/GFAP-positive cells and S100A10 protein expression. CONCLUSION: Our results first found that CSO treatment alleviated ischemic stroke injury by reducing microglial and astrocytic activation and inflammation, which was related to the inhibition of TLR4/NF-κB pathway and the reduction of A1 phenotype neurotoxic astrocyte activation, suggesting that CSO could be a new strategy in the prevention of ischemic stroke.


Assuntos
Astrócitos/efeitos dos fármacos , Óleo de Sementes de Algodão/farmacologia , Inflamação/tratamento farmacológico , AVC Isquêmico/tratamento farmacológico , Microglia/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Animais , Astrócitos/metabolismo , Óleo de Sementes de Algodão/uso terapêutico , Citocinas/metabolismo , Inflamação/metabolismo , AVC Isquêmico/metabolismo , Masculino , Microglia/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fármacos Neuroprotetores/uso terapêutico , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
6.
Nutr Res ; 60: 43-53, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30527259

RESUMO

Modifying dietary fat composition is important for minimizing cardiovascular disease risk. The purpose of this study was to determine the effects of a 5-day, high-fat diet rich in cottonseed oil (CSO) or olive oil (OO) on lipid profiles. Based on previous human and animal models, we hypothesized that the CSO-rich diet would lead to lower fasting and postprandial lipid levels, whereas the OO-rich diet would not significantly change lipid levels in 5 days. Fifteen normal-weight men completed a randomized crossover design with 2 controlled feeding trials (3-day lead-in diet, prediet visit, 5-day CSO- or OO-rich diet, postdiet visit). The 5-day diets (50% fat) were rich in either CSO or OO. At pre- and postdiet visits, subjects consumed test meals rich in the oil that coincided with their 5-day diet, and blood draws were performed. Fasting total cholesterol, low-density lipoprotein cholesterol, and triglycerides (TG) were lower following CSO diet intervention (total cholesterol: 148.40 ±â€¯6.39 to 135.93 ±â€¯6.31 mg/dL; low-density lipoprotein cholesterol: 92.20 ±â€¯5.57 to 78.13 ±â€¯5.60 mg/dL; TG: 80.11 ±â€¯4.91 to 56.37 ±â€¯5.46 mg/dL for pre- to postdiet, respectively; P < .05). High-density lipoprotein cholesterol increased following CSO diet intervention (46.67 ±â€¯2.41 to 50.24 ±â€¯2.20 mg/dL for pre- to postdiet, respectively; P < .05). Postprandial TGs were lower following CSO diet (area under the curve of 954.28 ±â€¯56.90 vs 722.16 ±â€¯56.15 mg/dL/8 h for pre- vs postdiet, respectively; P < .01). No changes in blood lipids were found following OO diet. A 5-day CSO-rich diet led to improvements in cholesterol and TGs, whereas no changes were observed with an OO-rich diet.


Assuntos
Colesterol/sangue , Óleo de Sementes de Algodão/farmacologia , Dieta Hiperlipídica , Azeite de Oliva/farmacologia , Triglicerídeos/sangue , Adolescente , Adulto , Área Sob a Curva , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Jejum , Humanos , Período Pós-Prandial , Valores de Referência , Adulto Jovem
7.
Sci Rep ; 8(1): 10458, 2018 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-29993017

RESUMO

Cottonseeds are classified as glanded or glandless seeds depending on the presence or absence of gossypol glands. Glanded cottonseed has anticancer property and glandless cottonseed was reported to cause cancer in one animal study. It is important to investigate the effect of bioactive components from cottonseeds. Our objectives were to isolate ethanol extracts from cottonseeds and investigate their effects on human cancer cells. A protocol was developed for isolating bioactive extracts from seed coat and kernel of glanded and glandless cottonseeds. HPLC-MS analyzed the four ethanol extracts but only quercetin was identified in the glandless seed coat extract. Residual gossypol was detected in the glanded and glandless seed kernel extracts and but only in the glanded seed coat extract. Ethanol extracts were used to treat human cancer cells derived from breast and pancreas followed by MTT assay for cell viability. Ethanol extracts from glanded and glandless cottonseed kernels and gossypol significantly decreased breast cancer cell mitochondrial activity. Ethanol extract from glanded cottonseed kernel and gossypol also significantly decreased pancreas cancer cell mitochondrial activity. These results suggest that ethanol extracts from cottonseeds, like gossypol, contain anticancer activities.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Óleo de Sementes de Algodão/farmacologia , Gossipol/farmacologia , Neoplasias Pancreáticas/tratamento farmacológico , Extratos Vegetais/farmacologia , Antineoplásicos/farmacologia , Neoplasias da Mama/patologia , Sobrevivência Celular/efeitos dos fármacos , Óleo de Sementes de Algodão/química , Gossipol/análise , Humanos , Mitocôndrias/efeitos dos fármacos , Neoplasias Pancreáticas/patologia , Extratos Vegetais/química
8.
J Anim Sci ; 95(7): 3057-3067, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28727094

RESUMO

Diets containing more than 20% distiller's dried grains with solubles (DDGS) reduce fat firmness in pork, but supplementation of cottonseed oil or crude glycerol may improve fat firmness. The objective of this study was to assess the effect of feeding minimally refined cottonseed oil or crude glycerol on growth performance, carcass composition, and fat quality of growing-finishing pigs. Mixed sex pigs ( = 216; 24 ± 4 kg initial BW) were blocked by BW and allotted to 1 of 3 dietary treatments: 1) a basal corn-soybean meal diet with 40% DDGS (CON), 2) CON diet plus 5% minimally refined cottonseed oil added throughout the experiment (COT), or 3) CON fed during the first 8 wk and CON + 8% crude glycerol fed during the last 6 wk of the experiment (GLY). Although diets were not isocaloric, total AA-to-ME ratios were calculated to be equal among diets. Carcass composition was estimated using real-time ultrasound 2 d before harvest. Gilts (16/treatment) closest to the mean BW of each pen were harvested (115 ± 8 kg BW), and bellies were retrieved for in-depth analysis of fat quality. Belly fat was sampled and analyzed for fatty acid composition. Overall, ADFI of pigs fed COT (2.30 kg/d) was less ( < 0.01) than that of pigs fed CON or GLY (2.47 and 2.49 kg/d, respectively). Pigs fed COT (0.93 kg/d) had greater ( < 0.01) ADG compared with pigs fed CON or GLY (0.88 and 0.87 kg/d, respectively). Greater ( < 0.01) G:F was observed for pigs fed COT (0.41) than for pigs fed CON or GLY diets (0.36 and 0.35, respectively). Final BW of pigs fed COT (124.3 kg) was greater ( < 0.01) than that of pigs fed CON or GLY (118.9 and 118.6 kg, respectively). Pigs fed COT had greater ( < 0.01) HCW (94.9 kg) compared with pigs fed CON or GLY (89.9 and 89.2 kg, respectively). No differences were observed for dressing percentage (75.7, 76.3, and 75.3%), fat-free carcass lean percentage (50.5, 49.7, and 50.0%), and belly flop angle (6.21, 8.57, and 6.06°) for CON, COT, and GLY, respectively. Pigs assigned to COT had higher ( < 0.01) melting point of belly fat compared with pigs assigned to CON or GLY (30.4 vs. 26.3 and 25.3°C, respectively). Pigs fed COT had increased ( < 0.05) SFA, PUFA, and iodine value (IV) compared with CON-fed pigs. Glycerol supplementation had no influence on SFA, MUFA, and PUFA concentrations or IV of belly, jowl, and back fat compared with CON. In conclusion, COT diets improved growth performance due to greater energy density, but carcass composition was not affected by treatments. In this experiment, feeding neither COT nor GLY improved fat firmness of pigs fed diets containing 40% DDGS.


Assuntos
Óleo de Sementes de Algodão/farmacologia , Suplementos Nutricionais , Glicerol/farmacologia , Carne Vermelha/normas , Suínos/fisiologia , Tecido Adiposo/efeitos dos fármacos , Ração Animal/análise , Animais , Dieta/veterinária , Metabolismo Energético , Ácidos Graxos/farmacologia , Feminino , Iodo/farmacologia , Masculino , Glycine max , Suínos/crescimento & desenvolvimento , Zea mays
9.
Anticancer Res ; 33(3): 949-55, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23482766

RESUMO

BACKGROUND: Breast cancer is the most commonly diagnosed cancer in women. Obesity is an important risk factor for developing breast cancer and is one of few risk factors that women can modify to prevent cancer. (-)-Gossypol-enriched cottonseed oil [(-)-GPCSO] contains 65% (-)-gossypol and 35% (+)-gossypol. Previous studies have demonstrated that both (-)-gossypol and (-)-GPCSO have potent anticancer activity against multiple types of cancer, including breast cancer. In addition, (-)-GPCSO reduced body weight gain and food intake in young female rats. However, the role of (-)-GPCSO on adipogenesis in human breast pre-adipocytes remains unclear. MATERIALS AND METHODS: Primary human breast pre-adipocytes were induced to differentiate in adipogenic medium in the presence of (-)-GPCSO. The proliferation of pre-adipocytes was determined with a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2-H-tetrazolium (MTS) assay. Lipid accumulation and glycerol 3-phosphate dehydrogenase (GPDH) activity were measured during adipocyte differentiation. mRNA expression of cyclin-D1, B-cell lymphoma-2 (BCL-2), Peroxisome Proliferator-Activated Receptor-γ (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα) and leptin was analyzed by real-time PCR. RESULTS: (-)-GPCSO inhibited proliferation of pre-adipocytes and down-regulated the expression of cyclin-D1 and BCL-2. (-)-GPCSO also significantly decreased adipogenesis, as determined by inhibition of GPDH activity, triglyceride content (TG), and down-regulation of the expression of PPARγ, C/EBPα and leptin. CONCLUSION: These findings suggest that (-)-GPCSO has the potential as a food supplement to inhibit adipogenesis, and therefore, reduce obesity.


Assuntos
Adipócitos/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Mama/efeitos dos fármacos , Óleo de Sementes de Algodão/farmacologia , Gossipol/farmacologia , Células-Tronco/efeitos dos fármacos , Adipócitos/citologia , Mama/citologia , Mama/metabolismo , Proteína alfa Estimuladora de Ligação a CCAAT/genética , Proliferação de Células/efeitos dos fármacos , Ciclina D1/genética , Feminino , Genes bcl-2 , Humanos , Leptina/genética , PPAR gama/genética
10.
Pharm Res ; 28(12): 3256-64, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21710341

RESUMO

PURPOSE: We have demonstrated that (-)-gossypol-enriched cottonseed oil [(-)-GPCSO] can down-regulate Bcl-2 expression in MCF-7 and primary cultured human breast cancer epithelial cells (PCHBCECs). However, this agent has not been evaluated in vivo due to its limited solubility. We aimed to develop liposomes containing (-)-GPCSO to suppress Bcl-2/Bcl-xL expression. METHODS: (-)-GPCSO liposomes were prepared and evaluated for effects on breast cancer cell viability, MDA-MB-231 xenograft tumor growth, cellular Bcl-2 and Bcl-xL mRNA levels, and chemosensitivity to paclitaxel. RESULTS: (-)-GPCSO liposomes prepared had excellent stability. Cytotoxicity of (-)-GPCSO liposomes was significantly reduced compared to (-)-GPCSO in culture medium. Bcl-2 and Bcl-xL mRNA expression was down-regulated by (-)-GPCSO in culture medium or (-)-GPCSO liposomes in MDA-MB-231 cells. In PCHBCECs, Bcl-2 and Bcl-xL expression were down-regulated by (-)-GPCSO liposomes. (-)-GPCSO in culture medium induced only a mild reduction in Bcl-xL. In the MDA-MB-231 xenograft tumor model, (-)-GPCSO liposomes exhibited tumor-suppressive activity and significantly reduced intratumoral Bcl-2 and Bcl-xL expression. Cytotoxicity of paclitaxel was increased by pretreatment with (-)-GPCSO liposomes in MDA-MB-231 and PCHBCECs. CONCLUSIONS: Findings suggest that (-)-GPCSO liposomes warrant continued investigation as a chemosensitizer for breast cancers exhibiting Bcl-2-/Bcl-xL-mediated drug resistance.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Óleo de Sementes de Algodão/uso terapêutico , Gossipol/uso terapêutico , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteína bcl-X/genética , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/farmacologia , Mama/efeitos dos fármacos , Mama/metabolismo , Mama/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Óleo de Sementes de Algodão/administração & dosagem , Óleo de Sementes de Algodão/farmacologia , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Gossipol/administração & dosagem , Gossipol/farmacologia , Humanos , Lipossomos , Camundongos , Camundongos Nus , Paclitaxel/farmacologia , Células Tumorais Cultivadas
11.
Int J Mol Med ; 26(1): 113-9, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20514430

RESUMO

Induction of apoptosis is one of the mechanisms of chemotherapeutic agents against breast cancer. In addition, recent studies have shown that diets containing polyphenolic components possess anticancer activities either in vitro or in vivo by inhibiting cell proliferation and inducing apoptosis. The aim of our study was to explore the effects of (-)-gossypol-enriched cottonseed oil [(-)-GPCSO], a polyphenolic compound, on the proliferation of the breast cancer cell line MCF-7 as well as primary cultured human breast cancer epithelial cells (PCHBCEC). We investigated whether the mechanism of the effects of (-)-GPCSO was mediated via the induction of cell apoptosis and the regulation of Bcl-2 gene expression at both the mRNA and protein levels. Our results showed that (-)-GPCSO inhibited the proliferation of MCF-7 and PCHBCEC in a dose-dependent manner. (-)-GPCSO (0.1 and 0.2%) induced DNA fragmentation in both MCF-7 cells and PCHBCEC. (-)-GPCSO suppressed the expression of Bcl-2 at both the mRNA and protein levels in MCF-7 cells and PCHBCEC in a dose-dependent fashion. Our results suggest that the growth inhibitory effect of (-)-GPCSO on MCF-7 and PCHBCEC is due, at least partially, to the induction of cell apoptosis, which is mediated by down-regulation of Bcl-2 expression at both the mRNA and protein levels. It might be possible for (-)-GPCSO to be developed as a novel chemotherapeutic agent for breast cancer patients.


Assuntos
Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Óleo de Sementes de Algodão/farmacologia , Gossipol/farmacologia , Western Blotting , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Células Cultivadas , Óleo de Sementes de Algodão/química , Fragmentação do DNA/efeitos dos fármacos , Relação Dose-Resposta a Droga , Eletroforese em Gel de Ágar , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Feminino , Gossipol/química , Humanos , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa
12.
Anticancer Res ; 30(2): 439-44, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20332451

RESUMO

Sera from chickens that consumed a known level of (-)-gossypol (-)-GP) exhibited bioactivity against human breast cancer cells in vitro. Based on this, it is conceivable that similar anti-breast cancer activities of different magnitudes will be exhibited in biological samples harvested from (-)-GP-fed layer hens. The experimental data generated in this study may influence the fundamental thinking regarding the utilization of low cost agricultural commodities such as (-)-GP cottonseed meal to produce value-added chemopreventive animal products.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Galinhas/sangue , Anticoncepcionais Masculinos/farmacologia , Gossipol/farmacologia , Miosinas/metabolismo , Ração Animal , Fenômenos Fisiológicos da Nutrição Animal , Animais , Neoplasias da Mama/sangue , Neoplasias da Mama/patologia , Galinhas/crescimento & desenvolvimento , Óleo de Sementes de Algodão/farmacologia , Feminino , Humanos , L-Lactato Desidrogenase , Testes de Função Hepática , Células Tumorais Cultivadas
13.
FEBS Lett ; 581(13): 2541-8, 2007 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-17499720

RESUMO

We previously reported that daily intraperitoneal injections of oleamide weakly inhibits the spontaneous metastasis of BL6 cells by blocking the gap junction-mediated intercellular communications (GJIC) of connexin 26 (Cx26). In the present study, we tested camellia oil, olive oil and cottonseed oil which are rich in oleamide-like oleic acid for their inhibitory potency on Cx26-mediated GJIC and spontaneous metastasis of BL6 cells. We found that camellia oil, olive oil and cottonseed oil, and their distillate fractions inhibited Cx26-mediated GJIC. We also showed that daily intraperitoneal injection of camellia oil and its distillate fractions more potently inhibited spontaneous lung metastasis of BL6 cells than oleamide. Moreover, a daily oral administration of camellia oil distillate fraction effectively inhibited spontaneous metastasis. Notably, even camellia Tempura-oil, a commercially available food, weakly inhibited the spontaneous metastasis of BL6 cells. Since these oils are used as foods and are quite safe, we propose that they could be used as supplements to protect patients from lung metastasis of melanomas.


Assuntos
Camellia , Melanoma/patologia , Metástase Neoplásica/prevenção & controle , Óleos de Plantas/farmacologia , Animais , Linhagem Celular Tumoral , Óleo de Sementes de Algodão/farmacologia , Junções Comunicantes/efeitos dos fármacos , Junções Comunicantes/fisiologia , Camundongos , Azeite de Oliva , Fitoterapia , Óleos de Plantas/química
14.
Anticancer Res ; 27(1A): 107-16, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17352222

RESUMO

BACKGROUND: Multidrug resistance (MDR) is a major impediment to successful cancer chemotherapy. P-glycoprotein (P-gp), the product of the multidrug resistance 1 (MDR1) gene, acts as an efflux pump and prevents sufficient intracellular accumulation of several anticancer agents, thus, playing a major role in MDR. Tamoxifen (Tam), ICI 182 780 (ICI) and Adriamycin (Adr) alone or with (-)-gossypol-enriched cottonseed oil [(-)-GPCSO] possible effects on cell growth inhibition and regulation of MDR1, mRNA and P-gp expression were examined in both an MDR human breast cancer cell line, MCF-7/Adr cells, and primary cultured human breast cancer epithelial cells (PCHBCEC). MATERIALS AND METHODS: Cells were treated with 0.05% of (-)-GPCSO either in the absence or presence of either 0.1 microM Tam, ICI or Adr for 24 h. RESULTS: Using the non-radioactive cell proliferation MTS assay, none of these chemotherapeutic agents alone inhibited MCF-7/Adr cell and PCHBCEC proliferation; meanwhile, the combination of 0.1 microM Tam, ICI or Adr with 0.05% (-)-GPCSO significantly reduced MCF-7/Adr cell growth by approximately 34%, 32% and 23%, respectively, of that of the vehicle-treated cells. For PCHBCEC, the combination of 0.05% (-)-GPCSO with 0.1 microM of Tam, ICI and Adr reduced cell growth to about 94%, 90%, and 71% respectively, of the vehicle treated PCHBCEC. Furthermore, (-)-GPCSO inhibited MDR1/P-gp expression in both MCF- 7/Adr and PCHBCEC in a dose-dependent manner. Our results provide insight into the MDR-reversing potential of (-)-GPCSO in human breast cancer cells resistant to current chemotherapeutic agents.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Óleo de Sementes de Algodão/farmacologia , Genes MDR/efeitos dos fármacos , Gossipol/farmacologia , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/biossíntese , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Óleo de Sementes de Algodão/administração & dosagem , Óleo de Sementes de Algodão/química , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacologia , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Sinergismo Farmacológico , Estradiol/administração & dosagem , Estradiol/análogos & derivados , Estradiol/farmacologia , Fulvestranto , Expressão Gênica/efeitos dos fármacos , Gossipol/administração & dosagem , Gossipol/química , Humanos , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Tamoxifeno/administração & dosagem , Tamoxifeno/farmacologia , Células Tumorais Cultivadas
15.
Niger Postgrad Med J ; 13(3): 203-5, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17066106

RESUMO

OBJECTIVE: The antispermatogenic and contraceptive importance of gossypol had been established in male animals, including man; in the present work, adult female Wistar rats weighing 110 - 160g were used to study the effect of cottonseed oil (gossypol) on oestrous cycle and ovulation. MATERIALS AND METHODS: Forty-five cyclic female rats were sorted randomly into three experimental groups of fifteen animals each. Oral doses of 20 and 40 mg/kg/body weight were administered once a day at 0900 hr for a period of 15 days. Vaginal swab of animals were taken each day between 0700 hr- 0900 hr to study their oestrous cycle; at the end of each cycle (4-5 days), a batch of 5 animals was sacrificed in each group to evaluate the number of ova shed. RESULTS: The results showed that gossypol had no disruptive effects on oestrous cycle; ovulation was not adversely affected, neither was there any significant reduction (p > 0.05) in the number of oocytes released. CONCLUSION: Because gossypol did not alter the oestrous cycle and ovulation patterns in the study animals, we suggest that certain factors exist in female animals that abolish or limit gossypol toxicity; these were extensively discussed.


Assuntos
Anticoncepcionais/farmacologia , Óleo de Sementes de Algodão/farmacologia , Ciclo Estral/efeitos dos fármacos , Ovulação/efeitos dos fármacos , Animais , Anticoncepcionais/administração & dosagem , Óleo de Sementes de Algodão/administração & dosagem , Feminino , Distribuição Aleatória , Ratos , Ratos Wistar
16.
J Dairy Sci ; 89(11): 4176-87, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17033004

RESUMO

Our objectives were to determine lactational and reproductive outcomes in response to increased milking frequency (MF), injection of estradiol cypionate (ECP), and treatment with bovine somatotropin (bST). Lactating dairy cows (n = 144) were blocked by lactation number (1 vs. 2+) and assigned randomly to a 2 x 2 x 2 factorial experiment consisting of 8 treatment combinations: 1) MF consisting of 4x daily milking (4x) for the first 30 d in milk (DIM) vs. 2x daily milking (2x), with all cows milked 2x after 30 DIM; 2) 10 mg of ECP given postpartum at 8 +/- 3 DIM versus controls that received ECP diluent (oil); and 3) biweekly bovine somatotropin (bST), starting sometime after 60 DIM, versus no bST. Ovulation before the first artificial insemination was synchronized by using Heatsynch (GnRH injection 7 d before PGF2alpha followed in 24 h by ECP), and cows were artificially inseminated after detected estrus or at 48 h after ECP, whichever came first. Pregnancy was assessed by transrectal ultrasonography 28 to 30 d after artificial insemination. Daily yield and weekly components of milk were measured during the first 90 DIM. Intervals to first and second postpartum ovulation were unaffected by treatment, but cows were in estrus earlier after 2x (24 +/- 4 d) than 4x (41 +/- 4 d) daily MF, and sooner after ECP (25 +/- 3 d) than after oil (39 +/- 4 d) treatment. Pregnancy rates among 4x cows increased for ECP versus oil (52.8 vs. 27.8%) more than for cows with 2x MF treated with ECP versus oil (50.0 vs. 39.4%). Increased MF increased daily milk yields and energy-corrected milk yields during the first 30 DIM. Although milk yields were increased acutely by ECP during the 10 d after its injection, subsequent milk yields were decreased for ECP-treated cows previously milked 4x daily. Treatment with bST increased overall daily milk yields most in cows previously milked 2x daily and treated with oil and those milked 4x daily and treated with ECP. We concluded that early postpartum ECP injection increased pregnancy rates, but generally had detrimental effects on milk yields after 30 DIM for ECP-treated cows previously milked 4x daily, unless those cows also were treated with bST.


Assuntos
Bovinos/fisiologia , Estradiol/análogos & derivados , Hormônio do Crescimento/farmacologia , Lactação/fisiologia , Reprodução/fisiologia , Animais , Anticoncepcionais Femininos/administração & dosagem , Anticoncepcionais Femininos/farmacologia , Óleo de Sementes de Algodão/administração & dosagem , Óleo de Sementes de Algodão/farmacologia , Indústria de Laticínios , Estradiol/administração & dosagem , Estradiol/farmacologia , Ciclo Estral/efeitos dos fármacos , Ciclo Estral/fisiologia , Feminino , Hormônio do Crescimento/administração & dosagem , Lactação/efeitos dos fármacos , Leite/química , Leite/metabolismo , Ovulação/efeitos dos fármacos , Ovulação/fisiologia , Gravidez , Taxa de Gravidez , Distribuição Aleatória , Reprodução/efeitos dos fármacos , Fatores de Tempo
17.
J Dairy Sci ; 85(11): 2823-30, 2002 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12487449

RESUMO

The effects of whole cottonseed (WCS) in the diet and the administration of bovine somatotropin (bST) on ovarian follicular dynamics and plasma progesterone (P4) concentrations were examined in cows during a period of synchronized follicular growth. Lactating Holstein cows (n = 28) were randomly assigned to treatments in a 2 x 2 factorial arrangement. Diets consisted of WCS (15% of dry matter) or no WCS, and bST at a dose of 0 or 208 mg/14 d. Dietary treatments began within 24 h of calving and bST treatments began within 7 d postpartum. Cows received GnRH at 65 +/- 3 d postpartum (d 0), PGF2alpha, (d 7), a second dose of GnRH (d 9), and were inseminated 16 h later (d 10). Ovarian changes were monitored daily by ultrasonography from d 0 to 9. On d 9,93% of cows had a preovulatory follicle and 86% ovulated. For Class 2 (6 to 9 mm) follicles, a diet x bST interaction was detected, with bST stimulating Class 2 follicles in cows fed WCS, but not in cows on the control diet. Neither diet nor bST affected numbers of Class 1 (2 to 5 mm) or Class 3 (> or = 10 mm) follicles or sizes of the subordinate and dominant follicles. During the luteal phase of the cycle, lactating cows fed WCS tended to have elevated concentrations of plasma P4, whereas bST was without effect. Plasma concentrations of high-density lipoprotein cholesterol were increased in cows fed WCS. Number and diameter of corpora lutea did not differ among treatments.


Assuntos
Bovinos/fisiologia , Óleo de Sementes de Algodão/farmacologia , Hormônio do Crescimento/farmacologia , Lactação/fisiologia , Folículo Ovariano/fisiologia , Ração Animal , Animais , Relação Dose-Resposta a Droga , Feminino , Hormônio do Crescimento/sangue , Inseminação Artificial/veterinária , Folículo Ovariano/diagnóstico por imagem , Folículo Ovariano/efeitos dos fármacos , Ovulação/efeitos dos fármacos , Ovulação/fisiologia , Gravidez , Progesterona/sangue , Distribuição Aleatória , Proteínas Recombinantes/sangue , Proteínas Recombinantes/farmacologia , Ultrassonografia
18.
J Anim Sci ; 79(6): 1533-9, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11424691

RESUMO

In a preceding study, complete substitution of fish meal protein with cottonseed meal (CM) protein did not affect the survival or growth rate of adult rainbow trout over a 6-mo period. Gossypol, a naturally occurring compound in cottonseeds, has an antifertility effect in terrestrial animals, but information regarding salmonid fish is lacking. Female rainbow trout in this experiment were fed diets with either 0, 25, 50, 75, or 100% (diets 1 to 5) of the fish meal protein replaced with CM protein until first maturation and spawning to study long-term effects on growth and reproduction. Feeding diets containing CM over a total period of 10 mo did not result in differences in growth and mortality compared to the control group (P > 0.05). Increased CM incorporation levels resulted in decreased (P < 0.05) blood hemoglobin (10.6 +/- 1.3, 8.4 +/- 1.8, 7.3 +/- 1.1, 6.9 +/- 0.8, and 5.6 +/- 1.4 g/dL) and hematocrit (49.6 +/- 3.9, 38.5 +/- 9.3, 34.4 +/- 3.7, 34.8 +/- 4.9 and 28.0 +/- 6.8%) levels in diets 1 to 5, respectively. The CM incorporation level had no effect (P > 0.05) on the number of eggs produced per female but led to a reduction (P < 0.05) in egg weight. Eyed stage survival of embryos was low in all dietary groups and did not show differences (P > 0.05). However, an increasing CM incorporation level led to a linear increase (P < 0.05) in the number of females that produced no viable embryos (23.1, 37.5, 42.9, 60.0, and 71.4%). Gossypol in the diet was absorbed by the female trout and transferred to the eggs (0, 2.2 +/- 0.5, 6.7 +/- 1.6, 10.6 +/- 4.2, and 20.0 +/- 2.6 micrograms/g in diets 1 to 5, respectively). A high concentration of gossypol remained in the juveniles at the swim-up stage (endogenous yolk-absorbed) (0.6 +/- 0.3, 2.4 +/- 0.3, 3.4 +/- 0.0, and 4.7 +/- 1.0 micrograms/g, diets 2 to 5, respectively). The findings suggest that replacement of the dietary fish meal protein with CM protein has no effect on fish growth and mortality but may lead to a reduction in reproductive performance in female rainbow trout.


Assuntos
Óleo de Sementes de Algodão/farmacologia , Dieta/veterinária , Gossipol/farmacologia , Troca Materno-Fetal , Oncorhynchus mykiss/crescimento & desenvolvimento , Reprodução/efeitos dos fármacos , Animais , Óleo de Sementes de Algodão/metabolismo , Proteínas Alimentares/metabolismo , Proteínas Alimentares/farmacologia , Estradiol/sangue , Feminino , Gossipol/metabolismo , Hemoglobinas/análise , Hidroxiprogesteronas/sangue , Ovulação/efeitos dos fármacos , Óvulo/efeitos dos fármacos , Gravidez , Testosterona/sangue
19.
Plant Foods Hum Nutr ; 56(1): 51-60, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11213168

RESUMO

Previous research has demonstrated that the total replacement of corn oil (CO) with cottonseed oil (CSO) in the diets of growing male rats results in a lowering of the total cholesterol (TC) concentration in the serum. It is not, however, known if a partial replacement of dietary CO with CSO would be sufficient to lower TC levels, nor is the effect of replacing dietary CO with CSO on other indices of cholesterol status (e.g., the levels of high-density lipoprotein cholesterol [HDL-C], non-HDL-C [i.e., very-low and low-density lipoprotein-cholesterol], or the TC/HDL-C ratio). Growing male rats were fed diets having CO, CSO, or a CO/CSO (1:1, w/w) oil mixture (OM) as the source of dietary oil (diet groups CO, CSO, and OM, respectively). There were no differences between CO and OM groups for TC, HDL-C, non-HDL-C, or the TC/HDL-C ratio. However, TC was significantly lower (p < or = 0.05) for the CSO group than the CO group (2.85 vs. 3.23 mmol/l, or 110 vs. 125 mg/dl, respectively) as was HDL-C (1.83 vs. 2.13 mmol/l, or 71 vs. 82 mg/dl, respectively), but there were no differences between these groups for non-HDL-C or the TC/HDL-C ratio. Diet had no effect on serum triglycerides (TGs) or on total liver content of either cholesterol or TGs. Thus, partial (50%) replacement of CO with CSO was without effect on any of these serum indices of cholesterol status, but total replacement resulted in lower TC and HDL-C, without affecting non-HDL-C or the TC/HDL-C ratio. Because, relative to CO, CSO has higher levels of saturated fatty acids but lower levels of monounsaturated and polyunsaturated fatty acids, the cholesterol-lowering effect of CSO appears to be unrelated to its fatty acid composition, and may be caused by a component of its nonsaponifiable fraction.


Assuntos
Colesterol/sangue , Óleo de Milho/farmacologia , Óleo de Sementes de Algodão/farmacologia , Lipídeos/análise , Fígado/metabolismo , Animais , Óleo de Milho/administração & dosagem , Óleo de Milho/química , Óleo de Sementes de Algodão/administração & dosagem , Óleo de Sementes de Algodão/química , Gorduras na Dieta/administração & dosagem , Gorduras na Dieta/farmacologia , Hipercolesterolemia/tratamento farmacológico , Masculino , Ratos , Ratos Sprague-Dawley
20.
Biol Trace Elem Res ; 31(3): 215-22, 1991 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-1723612

RESUMO

Two experiments were conducted with day-old broiler chicks reared to 18 or 19 d of age. The objectives were: (1) to examine the effects of the antioxidant ethoxyquin (EQ) on peroxidation in feeds containing fish oil (FO) or lead (Pb), and (2) to determine whether systemic effects of Pb, which are attributed to tissue peroxidation, can be reversed by dietary EQ. Experiment 1 was a 2 x 2 factorial arrangement with the factors being 4% dietary cottonseed oil (CSO) vs FO and dietary Pb as lead acetate trihydrate (0 vs 1000 ppm). Feed was mixed 1 d prior to initiation of the experiment and stored at 4 degrees C until it was placed in the feeders. Experiment 2 was a 2 x 2 x 2 factorial arrangement with the factors being 3.5% dietary oil (CSO vs FO), dietary Pb (0 vs 1000 ppm), and EQ (0 vs 75 ppm). Feed was mixed 1 d prior to initiation of the experiment and held at room temperature thereafter. Growth depression by FO and Pb was less pronounced in Experiment 1 than in Experiment 2. In Experiment 2, FO and Pb increased the concentration of feed peroxide, and the increases were prevented by EQ. The growth depression by FO was completely reversed by EQ. EQ reversal of Pb-induced growth depression, although substantial, was not complete. The FO diet without Pb had a peroxide content (12.4 meq/kg feed) similar to the CSO + Pb diet (12.3 meq/kg feed); however, growth was not similar (407 vs 213 g body weight at 19 d, respectively). The results suggest that the toxic effects of Pb are mediated by peroxidative alterations both in the feed and in tissues. The ability of EQ to reverse significantly Pb effects on growth suggests a systemic action of this antioxidant.


Assuntos
Antioxidantes/farmacologia , Gorduras Insaturadas na Dieta/farmacologia , Etoxiquina/farmacologia , Óleos de Peixe/farmacologia , Intoxicação por Chumbo/prevenção & controle , Chumbo/toxicidade , Animais , Peso Corporal/efeitos dos fármacos , Galinhas , Óleo de Sementes de Algodão/farmacologia , Dieta , Chumbo/administração & dosagem , Peroxidação de Lipídeos , Masculino
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