Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.184
Filtrar
1.
J Neuroimmune Pharmacol ; 19(1): 18, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38733535

RESUMO

Suppression of immune functions can be elicited by behavioural conditioning using drugs such as cyclosporin A or rapamycin. Nevertheless, little is known about the underlying mechanisms and generalisability of this phenomenon. Against this background, the present study investigated whether the pharmacological properties of fingolimod (FTY720), an immunosuppressive drug widely applied to treat multiple sclerosis, can be conditioned in rats by means of taste-immune associative learning. For this purpose, a conditioned taste avoidance paradigm was used, pairing the presentation of a novel sweet drinking solution (saccharin or sucrose) as conditioned stimulus (CS) with therapeutically effective doses of FTY720 as unconditioned stimulus (US). Subsequent re-exposure to the CS at a later time point revealed that conditioning with FTY720 induced a mild conditioned taste avoidance only when saccharin was employed as CS. However, on an immunological level, neither re-exposure with saccharin nor sucrose altered blood immune cell subsets or splenic cytokine production. Despite the fact that intraperitonally administered FTY720 could be detected in brain regions known to mediate neuro-immune interactions, the present findings show that the physiological action of FTY720 is not inducible by mere taste-immune associative learning. Whether conditioning generalises across all small-molecule drugs with immunosuppressive properties still needs to be investigated with modified paradigms probably using distinct sensory CS. Moreover, these findings emphasize the need to further investigate the underlying mechanisms of conditioned immunomodulation to assess the generalisability and usability of associative learning protocols as supportive therapies in clinical contexts.


Assuntos
Cloridrato de Fingolimode , Imunossupressores , Animais , Cloridrato de Fingolimode/farmacologia , Ratos , Imunossupressores/farmacologia , Masculino , Ratos Wistar , Leucócitos/efeitos dos fármacos , Aprendizagem da Esquiva/efeitos dos fármacos , Condicionamento Clássico/efeitos dos fármacos , Propilenoglicóis/farmacologia , Paladar/efeitos dos fármacos , Sacarina
2.
Carbohydr Res ; 538: 109101, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38574410

RESUMO

To achieve better-repurposed motifs, saccharin has been merged with biocompatible sugar molecules via a 1,2,3-triazole linker, and ten novel 1,2,3-triazole-appended saccharin glycoconjugates were developed in good yield by utilizing modular CuAAC click as regioselective triazole forming tool. The docking study indicated that the resulting hybrid molecules have an overall substantial interaction with the CAXII macromolecule. Moreover, the galactose triazolyl saccharin analogue 3h has a binding energy of -8.5 kcal/mol with 5 H-bonds, and xylosyl 1,2,3-triazolyl saccharin analogue 3d has a binding energy of -8.2 kcal/mol with 6 H-bond interactions and have exhibited the highest binding interaction with the macromolecule system.


Assuntos
Química Click , Sacarina , Química Click/métodos , Glicoconjugados/química , Triazóis/química , Simulação de Acoplamento Molecular
3.
Invest Ophthalmol Vis Sci ; 65(4): 5, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38558091

RESUMO

Purpose: We aimed to determine the impact of artificial sweeteners (AS), especially saccharin, on the progression and treatment efficacy of patients with neovascular age-related macular degeneration (nAMD) under anti-vascular endothelial growth factor (anti-VEGF-A) treatment. Methods: In a cross-sectional study involving 46 patients with nAMD undergoing intravitreal anti-VEGF therapy, 6 AS metabolites were detected in peripheral blood using liquid chromatography - tandem mass spectrometry (LC-MS/MS). Disease features were statistically tested against these metabolite levels. Additionally, a murine choroidal neovascularization (CNV) model, induced by laser, was used to evaluate the effects of orally administered saccharin, assessing both imaging outcomes and gene expression patterns. Polymerase chain reaction (PCR) methods were used to evaluate functional expression of sweet taste receptors in a retinal pigment epithelium (RPE) cell line. Results: Saccharin levels in blood were significantly higher in patients with well-controlled CNV activity (P = 0.004) and those without subretinal hyper-reflective material (P = 0.015). In the murine model, saccharin-treated mice exhibited fewer leaking laser scars, lesser occurrence of bleeding, smaller fibrotic areas (P < 0.05), and a 40% decrease in mononuclear phagocyte accumulation (P = 0.06). Gene analysis indicated downregulation of inflammatory and VEGFR-1 response genes in the treated animals. Human RPE cells expressed taste receptor type 1 member 3 (TAS1R3) mRNA and reacted to saccharin stimulation with changes in mRNA expression. Conclusions: Saccharin appears to play a protective role in patients with nAMD undergoing intravitreal anti-VEGF treatment, aiding in better pathological lesion control and scar reduction. The murine study supports this observation, proposing saccharin's potential in mitigating pathological VEGFR-1-induced immune responses potentially via the RPE sensing saccharin in the blood stream.


Assuntos
Neovascularização de Coroide , Degeneração Macular , Humanos , Camundongos , Animais , Receptor 1 de Fatores de Crescimento do Endotélio Vascular , Sacarina/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Edulcorantes , Estudos Transversais , Cromatografia Líquida , Espectrometria de Massas em Tandem , Neovascularização de Coroide/metabolismo , Degeneração Macular/metabolismo , RNA Mensageiro/genética , Injeções Intravítreas , Inibidores da Angiogênese/uso terapêutico
4.
Chemosphere ; 356: 141893, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38582168

RESUMO

Acesulfame (ACE), sucralose (SUC), cyclamate (CYC), and saccharin (SAC) are widely used artificial sweeteners that undergo negligible metabolism in the human body, and thus ubiquitously exist in wastewater treatment plants (WWTPs). Due to their persistence in WWTPs, ACE and SUC are found in natural waters globally. Wastewater samples were collected from the primary influent, primary effluent, secondary effluent, and final effluent of a WWTP in Alberta, Canada between August 2022 and February 2023, and the artificial sweeteners concentrations were measured by LC-MS/MS. Using wastewater-based epidemiology, the daily per capita consumption of ACE in the studied wastewater treatment plant catchment was estimated to be the highest in the world. Similar to other studies, the removal efficiency in WWTP was high for SAC and CYC, but low or even negative for SUC. However, ACE removal remained surprisingly high (>96%), even in the cold Canadian winter months. This result may indicate a further adaptation of microorganisms capable of biodegrading ACE in WWTP. The estimated per capita discharge into the environment of ACE, CYC, and SAC is low in Alberta due to the prevalent utilization of secondary treatment throughout the province, but is 17.4-18.8 times higher in Canada, since only 70.3% of total discharged wastewater in Canada undergoes secondary treatment.


Assuntos
Sacarose/análogos & derivados , Edulcorantes , Tiazinas , Eliminação de Resíduos Líquidos , Águas Residuárias , Poluentes Químicos da Água , Águas Residuárias/química , Edulcorantes/análise , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/metabolismo , Alberta , Tiazinas/análise , Sacarina/análise , Monitoramento Ambiental , Biodegradação Ambiental , Espectrometria de Massas em Tandem , Sacarose/análise , Sacarose/metabolismo
5.
eNeuro ; 11(4)2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38649278

RESUMO

Attending to salient sensory attributes of food, such as tastes that are new, displeasing, or unexpected, allows the procurement of nutrients without food poisoning. Exposure to new tastes is known to increase norepinephrine (NE) release in taste processing forebrain areas, yet the central source for this release is unknown. Locus ceruleus norepinephrine neurons (LC-NE) emerge as a candidate in signaling salient information about taste, as other salient sensory stimuli (e.g., visual, auditory, somatosensation) are known to activate LC neurons. To determine if LC neurons are sensitive to features of taste novelty, we used fiber photometry to record LC-NE activity in water-restricted mice that voluntarily licked either novel or familiar substances of differential palatability (saccharine, citric acid). We observed that LC-NE activity was suppressed during lick bursts and transiently activated upon the termination of licking and that these dynamics were independent of the familiarity of the substance consumed. We next recorded LC dynamics during brief and unexpected consumption of tastants and found no increase in LC-NE activity, despite their responsiveness to visual and auditory stimuli, revealing selectivity in LC's responses to salient sensory information. Our findings suggest that LC activity during licking is not influenced by taste novelty, implicating a possible role for non-LC noradrenergic nuclei in signaling critical information about taste.


Assuntos
Locus Cerúleo , Camundongos Endogâmicos C57BL , Norepinefrina , Paladar , Animais , Locus Cerúleo/fisiologia , Masculino , Norepinefrina/metabolismo , Paladar/fisiologia , Camundongos , Percepção Gustatória/fisiologia , Ácido Cítrico/metabolismo , Sacarina/administração & dosagem , Neurônios/fisiologia , Feminino , Comportamento Animal/fisiologia
6.
Arq Gastroenterol ; 61: e23100, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38511793

RESUMO

BACKGROUND: Alcoholic liver disease (ALD) and metabolic-dysfunction associated steatotic liver disease (MASLD) are common, and gut microbiota (GM) is involved with both. Here we compared GM composition in animal models of MASLD and ALD to assess whether there are specific patterns for each disease. METHODS: MASLD model- adult male Sprague Dawley rats, randomized into two groups: MASLD-control (n=10) fed a standard diet; MASLD-group (n=10) fed a high-fat-choline-deficient diet for 16 weeks. ALD model- adult male Wistar rats randomized: ALD-control (n=8) fed a standard diet and water+0.05% saccharin, ALD groups fed with sunflower seed and 10% ethanol+0.05% saccharin for 4 or 8 weeks (ALC4, n=8; ALC8, n=8). ALC4/8 on the last day received alcoholic binge (5g/kg of ethanol). Afterwards, animals were euthanized, and feces were collected for GM analysis. RESULTS: Both experimental models induced typical histopathological features of the diseases. Alpha diversity was lower in MASLD compared with ALD (p<0.001), and structural pattern was different between them (P<0.001). Bacteroidetes (55.7%), Firmicutes (40.6%), and Proteobacteria (1.4%) were the most prevalent phyla in all samples, although differentially abundant among groups. ALC8 had a greater abundance of the phyla Cyanobacteria (5.3%) and Verrucomicrobiota (3.2%) in relation to the others. Differential abundance analysis identified Lactobacillaceae_unclassified, Lachnospiraceae_NK4A136_group, and Turicibacter associated with ALC4 and the Clostridia_UCG_014_ge and Gastranaerophilales_ge genera to ALC8. CONCLUSION: In this study, we demonstrated that the structural pattern of the GM differs significantly between MASLD and ALD models. Studies are needed to characterize the microbiota and metabolome in both clinical conditions to find new therapeutic strategies. BACKGROUND: •Changes in the composition of the intestinal microbiota are related to the development of alcoholic liver disease and metabolic-dysfunction associated steatotic liver disease. BACKGROUND: •The diversity of the intestinal microbiota was lower in animals with MASLD compared to ALD. BACKGROUND: •The structural pattern of the intestinal microbiota was significantly different among the experimental groups. BACKGROUND: •Studies are needed to characterize the composition of the intestinal microbiota and metabolome to find new therapeutic strategies.


Assuntos
Fígado Gorduroso , Microbioma Gastrointestinal , Hepatopatias Alcoólicas , Ratos , Animais , Masculino , Sacarina , Ratos Sprague-Dawley , Modelos Animais de Doenças , Ratos Wistar , Hepatopatias Alcoólicas/microbiologia , Etanol
7.
Sci Total Environ ; 919: 170755, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38340820

RESUMO

Artificial sweeteners (ASs) entered the environments after application and emissions. Recent studies showed that some ASs had obesogenic risks. However, it remained unclear whether such risks are common and how they provoke such effects. Presently, the effects of 8 widely used ASs on lipid accumulation were measured in Caenorhabditis elegans. Potential mechanisms were explored with feeding and locomotion behavior, lipid metabolism and neural regulation. Results showed that acesulfame (ACE), aspartame (ASP), saccharin sodium (SOD), sucralose (SUC) and cyclamate (CYC) stimulated lipid accumulation at µg/L levels, showing obesogenic potentials. Behavior investigation showed that ACE, ASP, SOD, SUC and CYC biased more feeding in the energy intake aspect against the locomotion in the energy consumption one. Neotame (NEO), saccharin (SAC) and alitame (ALT) reduced the lipid accumulation without significant obesogenic potentials in the present study. However, all 8 ASs commonly disturbed enzymes (e.g., acetyl-CoA carboxylase) in lipogenesis and those (e.g., carnitine palmitoyl transferase) in lipolysis. In addition, ASs disturbed PPARγ (via expressions of nhr-49), TGF-ß/DAF-7 (daf-7) and SREBP (sbp-1) pathways. Moreover, they also interfered neurotransmitters including serotonin (5-HT), dopamine (DA) and acetylcholine (ACh), with influences in Gsα (e.g., via expressions of gsα-1, ser-7), glutamate (e.g., mgl-1), and cGMP-dependent signaling pathways (e.g., egl-4). In summary, environmental ASs commonly disturbed neural regulation connecting behavior and lipid metabolism, and 5 out of 8 showed clear obesogenic potentials. ENVIRONMENTAL IMPLICATION: Artificial sweeteners (ASs) are become emerging pollutants after wide application and continuous emission. Recent studies showed that some environmental ASs had obesogenic risks. The present study employed Caenorhabditis elegans to explore the influences of 8 commonly used ASs on lipid metabolisms and also the underlying mechanisms. Five out of 8 ASs stimulated lipid accumulation at µg/L levels, and they biased energy intake against energy consumption. The other three ASs reduced the lipid accumulation. ASs commonly disturbed lipogenesis and lipolysis via PPARγ, TGF-ß and SREBP pathways, and also influenced neurotransmitters with Gsα, glutamate and cGMP-dependent signaling pathways.


Assuntos
Caenorhabditis elegans , Metabolismo dos Lipídeos , Animais , PPAR gama/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Edulcorantes/análise , Sacarina , Ciclamatos , Glutamatos , Neurotransmissores , Fator de Crescimento Transformador beta/metabolismo , Lipídeos
8.
Psychopharmacology (Berl) ; 241(6): 1191-1203, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38383904

RESUMO

RATIONALE: Preclinical studies report attenuated ethanol-induced conditioned taste aversion (CTA) following chronic ethanol exposure, suggesting that tolerance develops to the aversive properties of ethanol. However, these studies are confounded by pre-exposure to the unconditioned stimulus (US; ethanol), which is well known to hinder conditioning. OBJECTIVES: This study was designed to determine whether chronic ethanol exposure produces tolerance to the aversive properties of ethanol in the absence of a US pre-exposure confound. METHODS: CTA was performed in adult male and female Long-Evans rats by pairing 0.1% ingested saccharin with an intraperitoneal injection of ethanol (1.5 or 2.0 g/kg) or saline. Rats were then rendered ethanol dependent using chronic intermittent ethanol (CIE) vapor exposure. Controls were exposed to room air (AIR). The effect of chronic ethanol on CTA expression and reconditioning were examined following vapor exposure. RESULTS: Prior to vapor exposure, both sexes developed CTA to a comparable degree with 2.0 g/kg producing greater CTA than 1.5 g/kg ethanol. Following vapor exposure, AIR controls exhibited an increase in CTA magnitude compared to pre-vapor levels. This effect was largely absent in CIE-exposed rats. Re-conditioning after vapor exposure facilitated increased CTA magnitude to a similar degree in AIR- and CIE-exposed males. In contrast, CTA magnitude was unchanged by re-conditioning in females. CONCLUSIONS: These data suggest that chronic ethanol does not facilitate tolerance to the aversive properties of ethanol but rather attenuates incubation of ethanol-induced CTA. Loss of CTA incubation suggests that CIE exposure disrupts circuits encoding aversion.


Assuntos
Aprendizagem da Esquiva , Etanol , Ratos Long-Evans , Sacarina , Paladar , Animais , Masculino , Etanol/administração & dosagem , Etanol/farmacologia , Feminino , Ratos , Aprendizagem da Esquiva/efeitos dos fármacos , Aprendizagem da Esquiva/fisiologia , Paladar/efeitos dos fármacos , Sacarina/administração & dosagem , Modelos Animais de Doenças , Alcoolismo/fisiopatologia , Relação Dose-Resposta a Droga , Condicionamento Clássico/efeitos dos fármacos , Condicionamento Psicológico/efeitos dos fármacos
9.
Br J Nutr ; 131(1): 63-72, 2024 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-37424288

RESUMO

The purpose of this study is to further investigate the relationship between sweetener exposure and the risk of endometrial cancer (EC). Up until December 2022, a literature search in an electronic database was carried out utilizing PubMed, Web of Science, Ovid, and Scopus. The odds ratio (OR) and 95 % confidence interval (CI) were used to evaluate the results. Sweeteners were divided into nutritional sweeteners (generally refers to sugar, such as sucrose and glucose) and non-nutritional sweeteners (generally refers to artificial sweeteners, such saccharin and aspartame). Ten cohort studies and two case-control studies were eventually included. The study found that in 12 studies, compared with the non-exposed group, the incidence rate of EC in the sweetener exposed group was higher (OR = 1·15, 95 % CI = [1·07, 1·24]). Subgroup analysis showed that in 11 studies, the incidence rate of EC in the nutritional sweetener exposed group was higher than that in the non-exposed group (OR = 1·25, 95 % CI = [1·14, 1·38]). In 4 studies, there was no difference in the incidence rate of EC between individuals exposed to non-nutritional sweeteners and those who were not exposed to non-nutritional sweeteners (OR = 0·90, 95 % CI = [0·81, 1·01]). This study reported that the consumption of nutritional sweeteners may increase the risk of EC, whereas there was no significant relationship between the exposure of non-nutritional sweeteners and the incidence of EC. Based on the results of this study, it is recommended to reduce the intake of nutritional sweeteners, but it is uncertain whether use of on-nutritional sweeteners instead of nutritional sweetener.


Assuntos
Neoplasias do Endométrio , Adoçantes não Calóricos , Feminino , Humanos , Aspartame/efeitos adversos , Neoplasias do Endométrio/epidemiologia , Neoplasias do Endométrio/etiologia , Adoçantes não Calóricos/efeitos adversos , Sacarina/efeitos adversos , Sacarose/efeitos adversos , Edulcorantes/efeitos adversos , Estudos Observacionais como Assunto
10.
Exp Clin Psychopharmacol ; 32(2): 158-172, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37535523

RESUMO

The present study used a rat choice model to test how cocaine or heroin economically interacted with two different nondrug reinforcers along the substitute-to-complement continuum. In Experiment 1, the nondrug alternative was the negative reinforcer timeout-from-avoidance (TOA)-that is, rats could press a lever to obtain a period of safety from footshock. One group of rats chose between cocaine and TOA and another group chose between heroin and TOA. The relative prices of the reinforcers were manipulated across phases while controlling for potential income effects. When cocaine was the reinforcer, rats reacted to price changes by increasing their allocation of behavior to the more expensive option, thereby maintaining relatively proportional intake of cocaine and TOA reinforcers across prices, suggesting these reinforcers were complements here. In contrast, when heroin became relatively cheap, rats increased allocation of income to heroin and decreased allocation of income to TOA, suggesting that heroin substituted for safety. Additionally, rats were willing to accept more footshocks when heroin was easily available. In Experiment 2, the nondrug alternative was saccharin, a positive reinforcer. Heroin and saccharin were complements, but there was no consistent effect of price changes on the allocation of behavior between cocaine and saccharin. As a model of the processes that could be involved in human drug use, these results show that drug-taking behavior depends on the type of drug, the type of nondrug alternative available, and the prices of both. (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Assuntos
Cocaína , Heroína , Humanos , Ratos , Animais , Heroína/farmacologia , Sacarina/farmacologia , Comportamento de Escolha , Autoadministração , Cocaína/farmacologia
11.
Behav Brain Res ; 459: 114800, 2024 02 29.
Artigo em Inglês | MEDLINE | ID: mdl-38061669

RESUMO

A first-order association can be formed between toxin-induced nausea and a context, as well as nausea and a taste cue. However, comparatively little is understood about second-order associations. The present study examined if the bacterial endotoxin, LPS, could impair the first- and second-order conditioning of context aversion (anticipatory nausea paradigm) and subsequent conditioned taste avoidance (two-bottle task). Adult male Long Evans rats were treated with LiCl (127 mg/kg, intraperitoneal [i.p.]) or vehicle control (NaCl) and then exposed to a distinct context for 4 first-order conditioning trials. LPS (200 µg/kg, i.p.) or NaCl were administered 24 h after each trial. Seventy-two h after the final first-order conditioning trial, rats underwent 2 second-order conditioning trials where they were treated with 2% saccharin (i.p.) and then exposed to the same context. Twenty-four h after the final second-order conditioning trial, rats were tested in a two-bottle task (2 trials), where they were given a choice between water and a palatable 0.2% saccharin solution. LiCl-treated rats demonstrated a context aversion by the 3rd conditioning trial in the anticipatory nausea paradigm. Rats previously exposed to LiCl also displayed a conditioned taste avoidance of saccharin within the two-bottle task. LPS attenuated first-order context aversion but did not alter either second-order context aversion or conditioned taste avoidance in the two-bottle task. This study demonstrated that a secondary association formed within an aversive context could result in a conditioned taste avoidance. Further, LPS may be able to attenuate primary conditioning, but not secondary conditioning.


Assuntos
Lipopolissacarídeos , Cloreto de Lítio , Ratos , Masculino , Animais , Lipopolissacarídeos/efeitos adversos , Cloreto de Lítio/efeitos adversos , Ratos Long-Evans , Sacarina/farmacologia , Paladar , Cloreto de Sódio , Aprendizagem da Esquiva , Náusea/induzido quimicamente
12.
Behav Processes ; 214: 104974, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38043720

RESUMO

Three experiments were conducted to investigate Conditioned Olfactory Preferences using orthonasal inhalation, which is a less explored perceptual pathway compared to retronasal inhalation. In these experiments, odors were impregnated onto plastic disks to prevent the subjects from consuming or tasting them. The reinforcers used were a sucrose solution (Caloric groups) and a saccharin solution (Non-Caloric groups). The influence of nutritional deprivation was analyzed, with unrestricted access to food throughout the procedure in Experiment 1, food restriction during the conditioning phase in Experiment 2, and limited access to food during the test phase in Experiment 3. The results revealed conditioned preferences using both sucrose and saccharin as reinforcers. Furthermore, dietary restriction reduced the conditioned preference induced by saccharin, but not the preference induced by sucrose. These findings are discussed in light of the potential differences between orthonasal and retronasal presentation of odors during conditioning.


Assuntos
Privação de Alimentos , Sacarina , Humanos , Sacarina/farmacologia , Olfato , Odorantes , Sacarose/farmacologia
13.
Minerva Surg ; 79(1): 92-99, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37987752

RESUMO

INTRODUCTION: Urinary bladder cancer is a frequent neoplasia in the urogenital system. Ageing and smoking are the two main risk factors, however, some chemical agents such as artificial sweeteners could act as initiators or promoters. EVIDENCE ACQUISITION: After identifying trends in scientific literature, we conducted a wide search in PubMed database and a meta-analysis was performed on extracted data to determine the role of artificial sweeteners in the development of urinary bladder cancer. EVIDENCE SYNTHESIS: Twenty-one full reports were enrolled from screening of PubMed database into final analysis involving 116,568 subjects in comparisons. Overall, 13,682 and 102,886 cases were identified for bladder cancer patients and healthy controls, respectively. Among artificial sweetener users, 12.5% was the incidence of bladder cancer. In the control group, 11.2% of cases suffered from urothelial carcinoma of the bladder. About 40.7% of the patients suffering from urinary neoplasms and 37.8% of the healthy cases were artificial sweetener users, respectively. There were only minor differences in overall descriptive data. The incidence of urinary bladder cancer among artificial sweetener users and control cases showed no risk difference (RD: 0.00, CI: -0.06 to 0.06). The frequency of artificial sweetener use among patients suffering from urinary bladder neoplasms and healthy subjects was compared which showed equal occurrences (OR: 0.96, CI: 0.79 to 1.17). CONCLUSIONS: According to our results, the carcinogenic risk of artificial sweeteners is not proven. Saccharin should not be kept as a promoter in urothelial malignant transformation.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Neoplasias Urológicas , Humanos , Edulcorantes/efeitos adversos , Neoplasias da Bexiga Urinária/induzido quimicamente , Neoplasias da Bexiga Urinária/epidemiologia , Carcinoma de Células de Transição/induzido quimicamente , Sacarina/efeitos adversos , Neoplasias Urológicas/induzido quimicamente
14.
Can J Physiol Pharmacol ; 102(2): 116-127, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37748201

RESUMO

Non-nutritive sweeteners are popular food additives owing to their low caloric density and powerful sweetness relative to natural sugars. Their lack of metabolism contributes to evidence proclaiming their safety, yet several studies contradict this, demonstrating that sweeteners activate sweet taste G protein-coupled receptors (GPCRs) and elicit deleterious metabolic functions through unknown mechanisms. We hypothesize that activation of GPCRs, particularly orphan receptors due to their abundance in metabolically active tissues, contributes to the biological activity of sweeteners. We quantified the response of 64 orphans to the sweeteners saccharin and sucralose using a high-throughput ß-arrestin-2 recruitment assay (PRESTO-Tango). GPR52 was the sole receptor that significantly responded to a mixture of sucralose and saccharin. Subsequent experiments revealed sucralose as the activating sweetener. Activation of GPR52 was concentration-dependent, with an EC50 of 0.23 mmol/L and an Emax of 3.43 ± 0.24 fold change at 4 mmol/L. GPR52 constitutively activates CRE pathways; however, we show that sucralose-induced activation of GPR52 does not further activate this pathway. Identification of this novel sucralose-GPCR interaction supports the notion that sucralose elicits off-target signaling through the activation of GPR52, calling into question sucralose's assumed lack of bioactivity.


Assuntos
Adoçantes não Calóricos , Edulcorantes , Edulcorantes/farmacologia , Adoçantes não Calóricos/farmacologia , Sacarina/farmacologia , beta-Arrestinas , Sacarose/farmacologia , Receptores Acoplados a Proteínas G
15.
Behav Processes ; 214: 104984, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38103808

RESUMO

Increased reinforcer motivation in rats has been repeatedly demonstrated following intermittent-access (IntA) training, where the reinforcer is only available for brief periods during a session, compared to continuous-access (ContA) training where the reinforcer is available throughout the session. The present study investigated whether different associations learned during training on the two procedures contributes to the effect. Two experiments tested the importance of the stimulus-response (S-R) and stimulus-outcome (S-O) associations between the IntA availability cues and the training response and reinforcer, respectively. In Exp. 1, separate groups of rats were trained to lever press for saccharin on the IntA or ContA procedures. Increased motivation for saccharin was observed in the IntA group on a later progressive ratio test where nosepoking was the operant (but not when lever pressing was the operant). The outcome of the nosepoke test suggests that a potential S-R association formed during IntA training was not critical for the effect. In Exp. 2, increased saccharin motivation (on nosepoke tests) after IntA training (with lever pressing) was observed regardless of the presence or absence of IntA availability cues, indicating that the S-O association formed during training is not critical for the effect either. Overall, these results suggest that the elemental associations learned on IntA procedures may not be what drives increased motivation observed after IntA training.


Assuntos
Reforço Psicológico , Sacarina , Ratos , Animais , Sacarina/farmacologia , Motivação , Condicionamento Operante , Aprendizagem , Autoadministração
16.
Nutrition ; 117: 112237, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37897982

RESUMO

Use of non-nutritive sweeteners (NNSs) has increased worldwide in recent decades. However, evidence from preclinical studies shows that sweetener consumption may induce glucose intolerance through changes in the gut microbiota, which raises public health concerns. As studies conducted on humans are lacking, the aim of this review was to gather and summarize the current evidence on the effects of NNSs on human gut microbiota. Only clinical trials and cross-sectional studies were included in the review. Regarding NNSs (i.e, saccharin, sucralose, aspartame, and stevia), only two of five clinical trials showed significant changes in gut microbiota composition after the intervention protocol. These studies concluded that saccharin and sucralose impair glycemic tolerance. In three of the four cross-sectional studies an association between NNSs and the microbial composition was observed. All three clinical trials on polyols (i.e, xylitol) showed prebiotic effects on gut microbiota, but these studies had multiple limitations (publication date, dosage, duration) that jeopardize their validity. The microbial response to NNSs consumption could be strongly mediated by the gut microbial composition at baseline. Further studies in which the potential personalized microbial response to NNSs consumption is acknowledged, and that include longer intervention protocols, larger cohorts, and more realistic sweetener dosage are needed to broaden these findings.


Assuntos
Microbioma Gastrointestinal , Adoçantes não Calóricos , Humanos , Edulcorantes/farmacologia , Sacarina/farmacologia , Estudos Transversais , Adoçantes não Calóricos/efeitos adversos , Adoçantes não Calóricos/análise
17.
Brain Res ; 1822: 148617, 2024 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-37805008

RESUMO

Conditioned taste aversion (CTA) is an essential ability for animals to consume food safely and is regulated by neuromodulatory systems including the dopamine, noradrenaline, serotonin, and acetylcholine systems. However, because few studies focused on a comprehensive understanding of whole-brain activities, how these neuromodulators contribute to the process of CTA remains an open issue. 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) can visualize activated regions within the whole brain simultaneously and noninvasively. This study aimed to understand the mechanisms of CTA, especially focusing on the retrieval process after CTA acquisition by FDG-PET imaging. CTA was established in rats who received an intraoral application of saccharin solution (IOAS) on the first day (Day 1), a LiCl i.p. injection after an IOAS on Day 2, and an IOAS on Day 3 (CTA group). The subtraction images of Day 3 of the SHAM group, which received a 0.9 % NaCl (saline) injection instead of a LiCl on Day 2, from those of Day 3 of the CTA group revealed increases in FDG signals in multiple brain regions including the substantia nigra, ventral tegmental area, locus coeruleus, dorsal raphe, and nucleus basalis magnocellularis, in addition to the hippocampus and nociception-related regions, including the parabrachial nucleus and solitary nucleus. On the other hand, the visceral pain induced by the LiCl injection increased FDG signals in the primary and secondary somatosensory and insular cortices in addition to the parabrachial nucleus and solitary nucleus. These results suggest that the retrieval process of CTA induces brain regions producing neuromodulators and pain-related brainstem.


Assuntos
Fluordesoxiglucose F18 , Paladar , Ratos , Animais , Paladar/fisiologia , Cloreto de Lítio , Aprendizagem da Esquiva/fisiologia , Núcleo Solitário , Sacarina/farmacologia , Tomografia por Emissão de Pósitrons , Neurotransmissores
18.
Neuropharmacology ; 242: 109770, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37858886

RESUMO

Alcohol Use Disorder (AUD) is a significant public health issue in the United States. It affects millions of individuals and their families and contributes to substantial societal and economic burdens. Despite the availability of some pharmacological treatments, there is still a pressing need to develop more effective therapeutic strategies to address the diverse range of symptoms and challenges associated with AUD. Catechol-O-methyltransferase (COMT) inhibition recently emerged as a promising new approach to treating AUD due to its potential to improve cognitive effects commonly associated with AUD. Tolcapone, an FDA-approved COMT inhibitor, has shown some promise for treating AUD; however, its ability to decrease drinking in ethanol-dependent rats has not been well-established. In this study, we evaluated the effects of tolcapone on operant, oral ethanol self-administration in non-dependent and dependent rats, and in rats that self-administered oral saccharin. To induce dependence, rats underwent the chronic intermittent exposure to vapor model, and their drinking levels were assessed during acute withdrawal from ethanol. Our results demonstrated that tolcapone attenuated responding for ethanol in dependent rats only, without affecting self-administration in non-dependent rats or rats self-administering saccharin. Moreover, we found that tolcapone was differentially effective in different estrous phases in female rats. These findings suggest that COMT inhibition, specifically using tolcapone, may be a valuable pharmacotherapy for treating AUD, particularly in individuals who are physically dependent on alcohol. Further research is needed to elucidate the precise mechanisms underlying the observed effects and to assess the potential of COMT inhibitors in a broader population of individuals with AUD.


Assuntos
Alcoolismo , Catecol O-Metiltransferase , Humanos , Ratos , Feminino , Animais , Tolcapona , Alcoolismo/tratamento farmacológico , Etanol , Sacarina , Benzofenonas/farmacologia , Benzofenonas/uso terapêutico , Nitrofenóis/farmacologia , Nitrofenóis/uso terapêutico , Inibidores de Catecol O-Metiltransferase/farmacologia , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico
19.
Neuropharmacology ; 242: 109765, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37863313

RESUMO

Significant exposure to alcohol or cannabis during adolescence can induce lasting disruptions of neuronal signaling in brain regions that are later to mature, such as the medial prefrontal cortex (mPFC). Considerably less is known about the effects of alcohol and cannabis co-use, despite its common occurrence. Here, we used male and female Long-Evans rats to investigate the effects of early-life exposure to ethanol, delta-9-tetrahydrocannabinol (THC), or their combination on high frequency stimulation (HFS)-induced plasticity in the prelimbic region of the mPFC. Animals were injected daily from postnatal days 30-45 with vehicle or THC (escalating doses, 3-20 mg/kg) and allowed to drink vehicle (0.1% saccharin) or 10% ethanol immediately after each injection. In vitro brain slice electrophysiology was then used to record population responses of layer V neurons following HFS in layer II/III after 3-4 weeks of abstinence. We found that THC exposure reduced body weight gains observed in ad libitum fed rats, and reduced intake of saccharin and ethanol. Compared to controls, there was a significant reduction in HFS-induced long-term depression (LTD) in rats exposed to either drug alone, and an absence of LTD in rats exposed to the drug combination. Bath application of indiplon or AR-A014418, which enhance GABAA receptor function or inhibit glycogen synthase kinase 3ß (GSK3ß), respectively, suggested the effects of ethanol, THC or their combination were due in part to lasting adaptations in GABA and GSK3ß signaling. These results suggest the potential for long-lasting adaptations in mPFC output following co-exposure to alcohol and THC.


Assuntos
Dronabinol , Alucinógenos , Ratos , Masculino , Feminino , Animais , Ratos Long-Evans , Dronabinol/farmacologia , Etanol/farmacologia , Glicogênio Sintase Quinase 3 beta , Sacarina , Córtex Pré-Frontal , Plasticidade Neuronal , Alucinógenos/farmacologia , Receptores de GABA-A/fisiologia , Agonistas de Receptores de Canabinoides/farmacologia
20.
Behav Processes ; 213: 104970, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37995950

RESUMO

Two experiments examined the hedonic responses conditioned to odor cues in the phenomenon of taste-potentiated odor aversion. Experiment 1 analyzed the microstructure of licking behavior during voluntary consumption. A tasteless odor (amyl acetate) was delivered to rats either diluted in water or mixed with saccharin before being injected with LiCl. At test, subjects which had received the odor-taste compound during conditioning showed both lower odor consumption and lick cluster size, a result indicating an increased negative evaluation of the odor. Experiment 2 examined the orofacial reactions elicited by the odor as index of its hedonic impact. During conditioning, the rats were intraorally infused with either the odor alone or the odor-saccharin compound before being injected with LiCl. At test, they were infused with the odor and their orofacial responses video recorded. More aversive orofacial responses were elicited by the odor cue in rats that had compound conditioning, again a result indicating a strengthened negative hedonic reactivity compared to animals experiencing odor aversion conditioning alone. Taken together, these results indicate that taste-mediated potentiation of odor aversion conditioning impacts on the acquisition of conditioned hedonic reactions as well as consumption.


Assuntos
Odorantes , Paladar , Humanos , Ratos , Animais , Paladar/fisiologia , Sacarina , Cloreto de Lítio , Aprendizagem da Esquiva/fisiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...