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1.
Trop Anim Health Prod ; 56(7): 251, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39225828

RESUMEN

The use of antibiotics as conventional feed additives in poultry operations have proven useful, however resulted serious health concerns to consumer due to their bio-accumulation, besides rising problem of antimicrobial resistance in microbes, thus, an alternative to antibiotic growth promoter have called for. One of the aim of the experiment was to assess the lone and combined effects of feeding of chitosan oligosaccharide (COS) and blend of organic acids and short chain fatty acids in essential oils on growth performance, haematological parameters, relative lymphoid organ weight and innate immunity in early aged layer chick (male birds). A total of ninety, day-old chicks were randomly allotted into five groups: CO, Control group fed only poultry feed ; AGP, antibiotic growth promoter fed Avilomycin at the dose of 200 mg/kg of poultry feed; CH, chitosan oligosaccharide fed at the rate of 100 mg/kg feed; OE, blend of organic acids and short chain fatty acids in essential oils contained 1000 to 2000 mg/kg feed in a graded dose per week and CH + OE, chitosan oligosaccharide plus blend of organic acids and short chain fatty acids in essential oils at consistent rate and manner as followed for each of given feed additives when fed individually. Data on growth performance, samples for haematological parameters and innate immunity were measured and assayed on 7th, 21st and 42nd day post feeding (dpf) respectively. The results showed that compared with the control group; there is a marginal gain in body weight at 7th and 21st dpf in CH group and the corresponding CH + OE group. Feed conversion ratio in CH group was remarkably good at 7th and 21st dpf. No significant difference was observed in relative organ weights of thymus, spleen and Bursa of Fabricius in treatment groups as compared to control birds; however a significant rise in splenic weight index in OE fed birds at 42nd dpf noted. Haematological changes were inconsequential in treatment groups with an exception to enhancement of heterophil to lymphocyte ratio (H:L ratio) in CH group at 42nd dpf. Serum lysozyme activity proportionately elevated in CH + OE group on 21st and 42nd dpf when measured against control group; on the other hand no detectable augmentation of gut lysozyme activity observed. Both serum bactericidal and gut bactericidal activity boosted in combinatorial group at 42nd dpf. These results indicated that early age feeding of chitosan individually or combination with organic acids and short chain fatty acids in layer chick is beneficial, as it has the potential to enhance body weight gain to some extent and improves systemic and localized innate immunity to offer protection against infectious assaults thus may avoid early chick mortality in farms.


Asunto(s)
Alimentación Animal , Pollos , Quitosano , Inmunidad Innata , Animales , Quitosano/administración & dosificación , Quitosano/farmacología , Pollos/crecimiento & desarrollo , Pollos/inmunología , Masculino , Inmunidad Innata/efectos de los fármacos , Alimentación Animal/análisis , Dieta/veterinaria , Suplementos Dietéticos/análisis , Distribución Aleatoria , Aceites Volátiles/administración & dosificación , Aceites Volátiles/farmacología , Tamaño de los Órganos/efectos de los fármacos , Oligosacáridos/administración & dosificación , Oligosacáridos/farmacología
2.
Psychopharmacol Bull ; 54(4): 18-34, 2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39263200

RESUMEN

Introduction: Lithium is a gold-standard agent for bipolar disorder (BD) and can affect the size, structure and/or function of thyroid gland with long-term exposure. Thyroid ultrasound can detect structural thyroid abnormalities, but it is under-reported with few prior studies in lithium users. The study aimed to evaluate thyroid volume and echogenicity in lithium users with BD and healthy participants, and explores its association with clinical variables and thyroid functions. Method: This was an observational study with 102 participants in total. Study group consisted of 52 clinically-stable (HAM-D ≤ 13, YMRS <8) follow-up patients with DSM-5 BD on lithium maintenance. Healthy controls (HC) comprised 50 participants with no illness in self and family. Assessments included NIMH Life-chart, IGLSI typical/atypical scale, lithium response scale (LRS) and CGI-BP. Fasting venous sample was taken for thyroid functions, Anti-TPO antibodies and serum lithium. Thyroid ultrasonography was also conducted. Results: Mean age of cases was 39.42 ± 12.62 years, with 42.3% females, which was comparable to HC. Median duration of illness was 10.5 years (Q1-Q3 = 6-19 years), with median lithium exposure for 4.5 years (Q1-Q3:2.2-7.75), and serum lithium 0.67 mmol/L (SD:0.31). Thyroid volume was significantly higher for cases than HC (10.67 ± 5.46 mL vs 4.30 ± 2.06 mL; p < 0.001). Relative to HC, serum TSH was higher in cases (p = 0.018), while anti-TPO positivity was comparable (14.0% vs 3.85%, p = 0.089). Thyroid nodules were more frequent in male cases (p = 0.013) compared to male controls.Thyroid volume did not show association with serum TSH (p = 0.277) and lithium response (p = 0.36). Conclusion: Findings indicate a uniform enlargement of thyroid gland in lithium users with BD. Thyroid volume did not show association with thyroid functions and lithium response, however prospective studies may give better insight about their trajectories over time.


Asunto(s)
Trastorno Bipolar , Glándula Tiroides , Ultrasonografía , Humanos , Masculino , Trastorno Bipolar/tratamiento farmacológico , Trastorno Bipolar/diagnóstico por imagen , Femenino , Adulto , Glándula Tiroides/diagnóstico por imagen , Glándula Tiroides/efectos de los fármacos , Persona de Mediana Edad , Estudios de Casos y Controles , Compuestos de Litio/administración & dosificación , Compuestos de Litio/farmacología , Antimaníacos/administración & dosificación , Antimaníacos/farmacología , Tamaño de los Órganos/efectos de los fármacos , Litio/administración & dosificación
3.
Endocrinol Diabetes Nutr (Engl Ed) ; 71(7): 308-316, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39182982

RESUMEN

OBJECTIVE: To investigate the overall effect of whey protein supplementation on skeletal muscle mass in adults with type 2 diabetes mellitus (T2DM). METHODS: Systematic review of reports on corporal muscle mass from clinical trials that assessed the use of whey protein supplementation by means of validated techniques in patients with T2DM. PubMed, SCOPUS, Web of Science, LILACS, and SciELO databases were searched up to April 2022. Risk of bias was assessed by the Cochrane Collaboration Risk of Bias tool. We conducted a qualitative synthesis of information. RESULTS: Four studies (424 participants) that met the selection criteria were identified out of 1,787 records. Of these, 3 studies assessed the total muscle mass using dual-energy X-ray absorptiometry (DXA), and 1 reported changes to the transverse diameter of the vastus lateralis muscle with ultrasound imaging. In the intervention groups, DXA assessments demonstrated an increase in total muscle mass in 3 studies and in the appendicular muscle mass in 2. Changes to the proportion of muscle mass were not seen in the DXA studies and only a discrete difference was seen in the comparative groups studied by ultrasound imaging. CONCLUSION: Following the administration of whey protein supplementation in patients with T2DM, a partially positive effect was seen in skeletal muscle mass gain with a moderate certainty of evidence.


Asunto(s)
Diabetes Mellitus Tipo 2 , Suplementos Dietéticos , Músculo Esquelético , Proteína de Suero de Leche , Adulto , Humanos , Absorciometría de Fotón , Administración Oral , Diabetes Mellitus Tipo 2/dietoterapia , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Músculo Esquelético/efectos de los fármacos , Tamaño de los Órganos/efectos de los fármacos , Ensayos Clínicos Controlados Aleatorios como Asunto , Proteína de Suero de Leche/administración & dosificación
4.
Behav Brain Res ; 474: 115172, 2024 10 02.
Artículo en Inglés | MEDLINE | ID: mdl-39094955

RESUMEN

The phytoestrogens daidzein and genistein are ubiquitous in human food. This study aimed to elucidate their anxiety-liked effects, their effects on the reproductive organs, and the molecular mechanism behind any anxiety-liked effects in intact adult male Wistar rats. These phytoestrogens are of interest due to their posited health benefits, particularly for female, but with some effect on males as well. This study comprised two experiments: (1) Male Wistar rats received either a vehicle, daidzein, or genistein (0.25, 0.50, or 1.00 mg/kg) by subcutaneously injection for four weeks. They were then tested for anxiety-liked behaviors. Then, the brain monoamines in anxiolytic rats were determined; (2) The modulation of gamma aminobutyric acid receptors by phytoestrogens was further analyzed by administration of diazepam to phytoestrogen-treated rats before behavioral tests. In the first experiment, the biological parameters measured, including body weight, daily food intake and reproductive organ weights were unaffected by either genistein or daidzein. However, anxiolytic-like effect was observed in the low-dose daidzein (0.25 mg/kg) group. Higher doses of daidzein or genistein of all doses had no effect. Further, the low-dose daidzein did not alter brain monoamine levels. In the second experiment, the anxiolytic-like behavior of daidzein-treated rats receiving diazepam did not differ from that of the rats treated with just diazepam or just daidzein. In conclusion, 4-week exposure to daidzein or genistein had no negative effects on the reproductive organs, body weight, food intake, anxiogenic-like behavior, or monoaminergic and diazepam-modulated GABAergic neurotransmissions of intact male rats. However, beneficial anxiolytic-like effects were apparent after low-dose treatment with daidzein.


Asunto(s)
Ansiolíticos , Ansiedad , Genisteína , Isoflavonas , Ratas Wistar , Animales , Masculino , Genisteína/farmacología , Genisteína/administración & dosificación , Ansiolíticos/farmacología , Ansiolíticos/administración & dosificación , Isoflavonas/farmacología , Isoflavonas/administración & dosificación , Ansiedad/tratamiento farmacológico , Ratas , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Relación Dosis-Respuesta a Droga , Fitoestrógenos/farmacología , Fitoestrógenos/administración & dosificación , Diazepam/farmacología , Ingestión de Alimentos/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Tamaño de los Órganos/efectos de los fármacos
5.
An Acad Bras Cienc ; 96(3): e20230561, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39140518

RESUMEN

Olanzapine (OLZ) is an antipsychotic medication used to treat postpartum psychiatric symptoms. It aimed to evaluate the effects of administering OLZ to lactating rats on testicular parameters of adult Wistar rats. Mothers received 2.5, 5 or 10 mg/kg until weaning. Adult male rats showed decrease in body weight, weight of testes, epididymis, prostate, seminal gland and gonadosomatic index when higher doses of OLZ were administered. Testicular volumetric parameters, as well as the length of seminiferous tubules, were also reduced in animals treated with the highest doses of OLZ. The diameter of the seminiferous tubules and the height of the seminiferous epithelium were reduced. There was also a relevant decrease in the population of Sertoli cells and a relevant reduction in the volume of individual Leydig cells. Histopathological analysis of the testes showed lesions compatible with testicular degeneration in rats treated with the highest dose of OLZ. There was a significant reduction in plasma testosterone levels in all treatments. It is noted, therefore, that the adverse impact on the testes of the highest doses of the drug during the neonatal period persisted into adulthood, with the dose of 2.5 mg/kg of OLZ proving to be safer than the others.


Asunto(s)
Antipsicóticos , Benzodiazepinas , Lactancia , Olanzapina , Ratas Wistar , Testículo , Testosterona , Animales , Masculino , Testículo/efectos de los fármacos , Lactancia/efectos de los fármacos , Femenino , Olanzapina/administración & dosificación , Antipsicóticos/farmacología , Antipsicóticos/administración & dosificación , Benzodiazepinas/farmacología , Benzodiazepinas/administración & dosificación , Testosterona/sangre , Ratas , Tamaño de los Órganos/efectos de los fármacos , Peso Corporal/efectos de los fármacos
6.
Placenta ; 154: 207-215, 2024 09 02.
Artículo en Inglés | MEDLINE | ID: mdl-39084172

RESUMEN

INTRODUCTION: This study investigates the association between maternal exposure to particulate matter (PM10) and nitric dioxide (NO2) during the first, second and third trimester and placental weight and birth weight/placental weight (BW/PW) ratio in twins at birth. METHODS: Cross-sectional data of 3340 twins from the East Flanders Prospective Twin Survey was used. Air pollutant exposure was estimated via spatial temporal interpolation. Univariable and multivariable mixed model analyses with a random intercept to account for the relatedness of newborns were conducted for twins with separate placentas. Twin pairs with one placental mass were studied with linear and logistic regression. RESULTS: In the third trimester, for each 10 µm/m3 increase in PM10 or NO2 placental weight decreased -19.7 g (95%-C.I. -35.1; -4.3) and -17.7 g (95%-C.I. -30.4; -0.5) respectively, in moderate to late preterm twins with separate placentas. Consequently, BW/PW ratio increased with higher air pollution exposure. PM10 exposure in the last week of pregnancy was associated with a higher odds ratio (OR) of 1.20 (95%-C.I. 1.00; 1.44) for a "small for gestational age placenta" (placental weight <10th percentile). Conversely, first trimester air pollutant exposure was associated with lower ORs of 0.55 (95%-C.I. 0.35; 0.88) and 0.60 (95%-C.I. 0.42; 0.84). DISCUSSION: The association of PM10 and NO2 on placental weight is trimester-specific, differs for twins with one versus two placentas and is most pronounced in moderate to late preterm twins. Longitudinal studies are needed to better understand the relationship between air pollutant exposure and placental weight evolution across different trimesters.


Asunto(s)
Contaminación del Aire , Exposición Materna , Placenta , Humanos , Femenino , Embarazo , Placenta/anatomía & histología , Placenta/patología , Placenta/efectos de los fármacos , Adulto , Exposición Materna/efectos adversos , Contaminación del Aire/efectos adversos , Tamaño de los Órganos/efectos de los fármacos , Estudios Transversales , Material Particulado/efectos adversos , Recién Nacido , Peso al Nacer/efectos de los fármacos , Trimestres del Embarazo , Gemelos , Estudios Prospectivos , Dióxido de Nitrógeno/efectos adversos , Dióxido de Nitrógeno/análisis , Embarazo Gemelar , Masculino , Contaminantes Atmosféricos/efectos adversos
7.
Food Chem Toxicol ; 191: 114846, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38960084

RESUMEN

2,4-dinitroaniline (2,4-D), a widely used dye intermediate, is one of the typical pollutants, and its potential health risks and toxicity are still largely unknown. To explore its subchronic oral toxicity, Wistar rats (equal numbers of males and females) were used as test animals, and a 90-day oral dosing experiment was conducted, divided into control group, low-dose group (0.055 mg/kg), medium-dose group (0.22 mg/kg), medium-high dose group (0.89 mg/kg), and high-dose group (3.56 mg/kg). The body weight data, clinical appearance, and drug reactions of each test rat within 90 days of dosing were recorded; morning urine samples were collected four times to test for eight urinary indicators; blood samples were collected to test for nineteen hematological indicators and sixteen biochemical indicators; tissue samples were collected for pathological analysis; moreover, the no-observed-adverse-effect level (NOAEL) was determined, and the benchmark dose method was used to support this determination and provide a statistical estimate of the dose corresponding. The results indicated that the chronic toxicity of 2,4-dinitroaniline showed certain gender differences, with the eyes, liver, and kidneys being the main potential target organs of toxicity. Moreover, the subchronic oral NOAEL for 2,4-dinitroaniline was determined to be 0.22 mg/kg body weight (0.22 mg/kg for males and 0.89 mg/kg for females), and a preliminary calculation of the safe exposure limit for human was 0.136 mg/kg. The research results greatly enriched the safety evaluation data of 2,4-dinitroaniline, contributing to a robust scientific foundation for the development of informed safety regulations and public health precautions.


Asunto(s)
Compuestos de Anilina , Nivel sin Efectos Adversos Observados , Ratas Wistar , Pruebas de Toxicidad Subcrónica , Animales , Compuestos de Anilina/toxicidad , Masculino , Femenino , Administración Oral , Ratas , Relación Dosis-Respuesta a Droga , Peso Corporal/efectos de los fármacos , Tamaño de los Órganos/efectos de los fármacos
8.
Food Chem Toxicol ; 191: 114867, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39002792

RESUMEN

Despite its widespread use as a stabilizer across various industries over the past several decades, the health effects of chronic exposure to PFOA are still unclear. We administered PFOA by oral gavage (0, 12.5, 50, and 200 µg/day/mouse, eight groups) to male and female mice for six months. Body weight gain decreased with dose accompanied by increased liver weight, and PFOA altered liver damage-related-blood biochemical indicators and induced pathological lesions, including hepatocellular hypertrophy, cholangiofibrosis, and centrilobular hepatocellular vacuolation. Loss of the Golgi apparatus, formation of lamellar body-like structures, and lipid accumulation were observed in the liver of PFOA-treated mice. We also cohabited five pairs of male and female mice for the last ten days of administration, dosed PFOA to dam up to 28 days after birth, and investigated effects on reproduction and development. The survival rate of pups and the sex ratio of surviving mice decreased significantly at the highest dose. PFOA tissue concentration increased with the dose in the parent mice's liver and the pups' blood and brain. Taken together, we suggest that PFOA primarily affects the liver and reproduction system and that disturbance in lipid metabolism and Golgi's structural stability may be involved in PFOA-induced toxicity.


Asunto(s)
Caprilatos , Fluorocarburos , Aparato de Golgi , Hígado , Reproducción , Animales , Fluorocarburos/toxicidad , Femenino , Masculino , Caprilatos/toxicidad , Ratones , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Aparato de Golgi/efectos de los fármacos , Aparato de Golgi/metabolismo , Reproducción/efectos de los fármacos , Administración Oral , Tamaño de los Órganos/efectos de los fármacos , Relación Dosis-Respuesta a Droga
9.
Parasitol Res ; 123(7): 281, 2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-39037636

RESUMEN

Although the negative impact of liver fluke (Fasciola hepatica) infection on production and health in cattle is generally accepted, results of individual research have been variable, ranging from important negative impacts on the animal to minimal or no impact. To add information on the impact of F. hepatica infection in growing cattle, weight gain and liver weight of young experimentally infected animals from seven controlled efficacy studies were analyzed. In each study, fluke naïve animals were inoculated with approximately 450 to 500 F. hepatica encysted metacercariae, blocked on body weight and randomly assigned into one untreated group (controls) and groups which were administered an experimental flukicide when the flukes were 4 weeks old (migrating) and sacrificed 8 weeks thereafter (12 weeks after inoculation). Data of groups which demonstrated >90% reduction of fluke counts following treatment and groups left untreated (total 103 and 47 animals, respectively) were compared. There was a significant (p < 0.0001) negative association between fluke count and weight gain while fluke count and liver weight and fluke count and relative liver weight were positively associated (p < 0.0001). Over the 8-week post-treatment period, flukicide-treated cattle had almost 15% more weight gain than the controls (50.9 kg vs. 44.4 kg; p = 0.0003). Absolute and relative liver weight was significantly (p < 0.0001) lower in flukicide-treated compared to untreated cattle. Overall, this analysis provided evidence of a substantial negative effect of early (migrating) liver fluke infection on the growth of young cattle, likely due to pathology of the liver and associated reduction in its function as the central organ for bioenergy and protein metabolism.


Asunto(s)
Enfermedades de los Bovinos , Fasciola hepatica , Fascioliasis , Hígado , Aumento de Peso , Animales , Bovinos , Fasciola hepatica/efectos de los fármacos , Fascioliasis/veterinaria , Fascioliasis/parasitología , Fascioliasis/tratamiento farmacológico , Enfermedades de los Bovinos/parasitología , Enfermedades de los Bovinos/tratamiento farmacológico , Hígado/parasitología , Aumento de Peso/efectos de los fármacos , Tamaño de los Órganos/efectos de los fármacos , Antihelmínticos/farmacología , Antihelmínticos/administración & dosificación , Carga de Parásitos , Resultado del Tratamiento
10.
Environ Toxicol Pharmacol ; 109: 104497, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38971513

RESUMEN

Perfluorobutane sulfonate is a short-chain PFAS that is a less toxic replacement for the rather more toxic long-chain perfluorooctane sulfonate. PFBS is widespread in the environment and has raised environmental and health concerns. The study goal was to investigate whether dietary ingestion of PFBS would induce hepatic damage. Sprague-Dawley rats were assigned to three PFBS treatment groups for 11 weeks followed by clinical markers analyses in the serum and liver. There was a significant increase in liver and body weights of PFBS rats. Total antioxidant capacity was significantly reduced in the PFBS-treated group. ALT levels increased based on concentration ingested. Close to 1000 gene transcripts were differentially expressed. Further, transmembrane transport and oxidation-reduction processes were the most up-regulated biological processes. Inflammatory genes were up-regulated in the exposed group and those associated with oxidative damage were down-regulated. In conclusion, PFBS ingestion produced mild effects in the liver of Sprague Dawley rats.


Asunto(s)
Fluorocarburos , Hígado , Ratas Sprague-Dawley , Transcriptoma , Animales , Fluorocarburos/toxicidad , Hígado/metabolismo , Hígado/efectos de los fármacos , Masculino , Transcriptoma/efectos de los fármacos , Contaminantes Ambientales/toxicidad , Ratas , Ácidos Sulfónicos/toxicidad , Alanina Transaminasa/sangre , Peso Corporal/efectos de los fármacos , Dieta , Tamaño de los Órganos/efectos de los fármacos
11.
Environ Res ; 258: 119476, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-38909949

RESUMEN

The present study aims to analyze the effects of developmental exposure to phthalates at environmentally relevant doses on the neural control of male and female reproduction. For this purpose, C57Bl/6J mice were exposed to di-(2-ethylexyl) phthalate (DEHP) alone (5 or 50 µg/kg/d), or DEHP (5 µg/kg/d) in a phthalate mixture. Exposure through diet started 6 weeks before the first mating and lasted until weaning of litters from the second gestation (multiparous dams). Analyses of offspring born from multiparous dams exposed to DEHP alone or in a phthalate mixture showed that females experienced a delayed pubertal onset, and as adults they had prolonged estrous cyclicity and reduced Kiss1 expression in the preoptic area and mediobasal hypothalamus. Male littermates showed a reduced anogenital distance and delayed pubertal onset compared with controls. However, in adulthood the weight of androgen-sensitive organs and hypothalamic Kiss1 expression were unaffected, suggesting normal functioning of the male gonadotropic axis. Developmental exposure to DEHP alone or in a phthalate mixture reduced the ability of intact males and ovariectomized and hormonally primed females to attract a sexual partner and to express copulatory behaviors. In addition, females were unable to discriminate between male and female stimuli in the olfactory preference test. Social interaction was also impaired in females, while locomotor activity and anxiety-like behavior in both sexes were unaffected by the treatment. The sexual deficiencies were associated with reduced expression of the androgen receptor in the preoptic area and progesterone receptor in the mediobasal hypothalamus, the key regions involved in male and female sexual behavior, respectively. Thus, the neural structures controlling reproduction are vulnerable to developmental exposure to phthalates at environmentally relevant doses in male and female mice. Adult females had an impaired gonadotropic axis and showed more affected behaviors than adult males.


Asunto(s)
Exposición a Riesgos Ambientales , Ácidos Ftálicos , Reproducción , Reproducción/efectos de los fármacos , Masculino , Femenino , Animales , Ratones , Ácidos Ftálicos/toxicidad , Exposición a Riesgos Ambientales/efectos adversos , Ratones Endogámicos C57BL , Peso al Nacer/efectos de los fármacos , Tamaño de los Órganos/efectos de los fármacos , Dietilhexil Ftalato/toxicidad , Conducta Sexual Animal/efectos de los fármacos , Efectos Tardíos de la Exposición Prenatal , Kisspeptinas/metabolismo
12.
Food Chem Toxicol ; 191: 114839, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38942165

RESUMEN

The human gut microbiome plays a crucial role in immune function. The synbiotic consortium or Defined Microbial Assemblage™ (DMA™) Medical Food product, SBD121, consisting of probiotic microbes and prebiotic fibers was designed for the clinical dietary management of rheumatoid arthritis. A 28-day repeated administration study was performed to evaluate the oral toxicity of SBD121 in male and female rats (age/weight at study start: 60 days/156-264 g) administered levels of 0, 4.96 x 1010, 2.48 x 1011, or 4.96 x 1011 colony forming units (CFU)/kg-bw. No treatment related changes were observed in ophthalmological effects, mortality, morbidity, general health and clinical observations, urinalysis, hematology, serum chemistry, absolute or relative organ weights, gross necropsy, or histopathology. A significant decrease in body weight was reported in females in the low and high-concentration groups, which corresponded in part with a significant decrease in food consumption. Results of the functional observation battery indicated front grip strength was significantly greater in the high-concentration males compared to the controls; however, this effect was not considered adverse. Based on these findings, the administration of the Medical Food SBD121 to male and female rats has a no-observable adverse effect level (NOAEL) at the highest level tested of 4.96 x 1011 CFU/kg-bw.


Asunto(s)
Inocuidad de los Alimentos , Simbióticos , Animales , Masculino , Femenino , Ratas , Simbióticos/administración & dosificación , Ratas Sprague-Dawley , Peso Corporal/efectos de los fármacos , Nivel sin Efectos Adversos Observados , Tamaño de los Órganos/efectos de los fármacos
13.
Toxicol Sci ; 201(1): 38-47, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38876971

RESUMEN

Perfluorononanoic acid (PFNA) is a commercially relevant, long-chain (8 fully fluorinated carbon) perfluorinated carboxylic acid. PFNA has limited terrestrial ecotoxicity data and is detected in humans, animals, and the environment. This study is the fourth in a series with the objective of investigating the toxicity of a suite of per- and polyfluoroalkyl substances (PFAS) detected on military installations in a mammal indigenous to North America. Peromyscus leucopus (white-footed mice, ∼25/sex/dose) were exposed via oral gavage to either 0, 0.03, 0.14, 1, or 3 mg PFNA/kg-d for 112 consecutive days (4 wk premating exposure followed by an additional 12 wk of exposure after onset of mating). Parental generation animals were assessed for potential reproductive and developmental effects, organ weight changes, thyroid modulation, and immunotoxicity. Pup weight and survival were assessed at postnatal days 0, 1, 4, 7, and 10. Change in liver weight was determined to yield the most sensitive dose response according to benchmark dose analysis, and serves as the most protective point of departure (BMDL = 0.37 mg/kg-d PFNA). Other effects of PFNA exposure included reduced formation of plaque-forming cells, which are indicative of functional immune deficits (BMDL = 2.31 mg/kg-d); decreased serum thyroxine (BMDL = 0.93 mg/kg-d) without changes in some other hormones; and increased stillbirths (BMDL = 0.61 mg/kg-d PFNA). Pup weight and survival were not affected by PFNA exposure. Combined with data from previous studies, data from Peromyscus provide a One Health perspective on health effects of PFAS.


Asunto(s)
Fluorocarburos , Hígado , Peromyscus , Animales , Hígado/efectos de los fármacos , Hígado/patología , Femenino , Fluorocarburos/toxicidad , Masculino , Tamaño de los Órganos/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Glándula Tiroides/efectos de los fármacos , Glándula Tiroides/patología , Reproducción/efectos de los fármacos , Ácidos Grasos
14.
Artículo en Inglés | MEDLINE | ID: mdl-38870606

RESUMEN

Jinmao Jiedu granule is a Chinese medicine preparation consisting of Actinidia valvata Dunn, Salvia chinensis Benth, Iphigenia indica Kunth, and chicken gizzard. For many years, it has been employed in adjuvant therapy for cancer, especially liver cancer. However, the potential toxicity of the granule has not been reported. The present study aimed to assess the repeated-dose toxicity of orally administered Jinmao Jiedu granules for Sprague-Dawley (SD) rats. SD rats were orally administered Jinmao Jiedu granules at doses of 2.85, 5.70, and 11.40 g/kg in a 28-day subchronic toxicity study. No adverse clinical signs associated with treatment were noted throughout the experiment. There were no treatment-related toxicity alterations in body weight, hematology, clinical biochemistry, urinalysis, necropsy, and histopathology in rats compared with the control group. The No Observed Adverse Effect Level (NOAEL) of the Jinmao Jiedu granule was higher than 11.40 g/kg/day in rats.


Asunto(s)
Medicamentos Herbarios Chinos , Ratas Sprague-Dawley , Animales , Medicamentos Herbarios Chinos/toxicidad , Medicamentos Herbarios Chinos/administración & dosificación , Ratas , Masculino , Administración Oral , Femenino , Nivel sin Efectos Adversos Observados , Peso Corporal/efectos de los fármacos , Pruebas de Toxicidad Subcrónica , Tamaño de los Órganos/efectos de los fármacos
15.
Bone ; 186: 117143, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38866125

RESUMEN

The effects of gender affirming hormone therapy (GAHT) on bone microarchitecture and fracture risk in adult transgender women is unclear. To investigate the concept that skeletal integrity and strength in trans women may be improved by treatment with a higher dose of GAHT than commonly prescribed, we treated adult male mice with a sustained, high dose of estradiol. Adult male mice at 16 weeks of age were administered ~1.3 mg estradiol by silastic implant, implanted intraperitoneally, for 12 weeks. Controls included vehicle treated intact females and males. High-dose estradiol treatment in males stimulated the endocortical deposition of bone at the femoral mid-diaphysis, increasing cortical thickness and bone area. This led to higher stiffness, maximum force, and the work required to fracture the bone compared to male controls, while post-yield displacement was unaffected. Assessment of the material properties of the bone showed an increase in both elastic modulus and ultimate stress in the estradiol treated males. Treatment of male mice with high dose estradiol was also anabolic for trabecular bone, markedly increasing trabecular bone volume, number and thickness in the distal metaphysis which was accompanied by an increase in the histomorphometric markers of bone remodelling, mineralizing surface/bone surface, bone formation rate and osteoclast number. In conclusion, a high dose of estradiol is anabolic for cortical and trabecular bone in a male to female transgender mouse model, increasing both stiffness and strength. These findings suggest that increasing the current dose of GAHT administered to trans women, while considering other potential adverse effects, may be beneficial to preserving their bone microstructure and strength.


Asunto(s)
Estradiol , Animales , Masculino , Estradiol/farmacología , Estradiol/sangre , Femenino , Ratones , Huesos/efectos de los fármacos , Huesos/diagnóstico por imagen , Densidad Ósea/efectos de los fármacos , Anabolizantes/farmacología , Tamaño de los Órganos/efectos de los fármacos , Ratones Endogámicos C57BL , Humanos , Modelos Animales , Microtomografía por Rayos X
16.
Food Chem Toxicol ; 190: 114843, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38944142

RESUMEN

Mulberry (Morus alba L) fruit is traditionally used in Chinese medicine and has several beneficial effects, such as hypoglycemic, hypolipidemic, and anti-oxidative effects. We previously developed the synbiotic mulberry (SM) containing probiotic Lactobacilli, prebiotic inulin, and mulberry powder. In food supplement development, toxicity is the most important criterion in food and drug regulations before commercialization. Thus, this study aimed to investigate the subchronic toxicity of SM in male and female Wistar rats to evaluate its biosafety. The subchronic toxicity study was conducted by daily oral administration of SM at doses of 250, 500, and 1000 mg/kgBW for 90 days. Male and female rats were evaluated for body weight, organ coefficients, biochemical and hematological parameters, and vital organ histology. The results showed no mortality or toxic changes in the subchronic toxicity study. These results suggested that no observed adverse effect level (NOAEL) of SM in male and female rats has been considered at 1000 mg/kgBW for subchronic toxicity study.


Asunto(s)
Morus , Simbióticos , Animales , Femenino , Masculino , Ratas , Administración Oral , Peso Corporal/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Morus/química , Nivel sin Efectos Adversos Observados , Tamaño de los Órganos/efectos de los fármacos , Ratas Wistar , Simbióticos/administración & dosificación , Pruebas de Toxicidad Subcrónica
17.
Zool Res ; 45(4): 805-820, 2024 07 18.
Artículo en Inglés | MEDLINE | ID: mdl-38894523

RESUMEN

The organ-specific toxicity resulting from microplastic (MP) exposure has been extensively explored, particularly concerning the gut, liver, testis, and lung. However, under natural conditions, these effects are not restricted to specific organs or tissues. Investigating whether MP exposure presents a systemic threat to an entire organism, impacting factors such as lifespan, sleep, and fecundity, is essential. In this study, we investigated the effects of dietary exposure to two different doses of MPs (1-5 µm) using the terrestrial model organism Drosophila melanogaster. Results indicated that the particles caused gut damage and remained within the digestive system. Continuous MP exposure significantly shortened the lifespan of adult flies. Even short-term exposure disrupted sleep patterns, increasing the length of daytime sleep episodes. Additionally, one week of MP exposure reduced ovary size, with a trend towards decreased egg-laying in mated females. Although MPs did not penetrate the brain or ovaries, transcriptome analysis revealed altered gene expression in these tissues. In the ovary, Gene Ontology (GO) analysis indicated genotoxic effects impacting inflammation, circadian regulation, and metabolic processes, with significant impacts on extracellular structure-related pathways. In the brain, GO analysis identified changes in pathways associated with proteolysis and carbohydrate metabolism. Overall, this study provides compelling evidence of the systemic negative effects of MP exposure, highlighting the urgent need to address and mitigate environmental MP pollution.


Asunto(s)
Drosophila melanogaster , Longevidad , Microplásticos , Ovario , Sueño , Animales , Drosophila melanogaster/efectos de los fármacos , Drosophila melanogaster/fisiología , Femenino , Ovario/efectos de los fármacos , Longevidad/efectos de los fármacos , Sueño/efectos de los fármacos , Microplásticos/toxicidad , Masculino , Tamaño de los Órganos/efectos de los fármacos
18.
Int. j. morphol ; 42(3): 663-672, jun. 2024. ilus, tab
Artículo en Inglés | LILACS | ID: biblio-1564620

RESUMEN

SUMMARY: Etoposide is an effective antimitotic and antineoplastic agent used to treat various human malignancies. In the present study, Etoposide was injected intraperitoneally into the rats at 1 mg/kg/day for 52 days (52 doses). The control animals received physiological saline (0.5 ml) intraperitoneally daily for 52 doses. The body weight of etoposide-treated rats was significantly reduced compared to control rats. Lipid peroxidation demonstrated an insignificant rise in hepatic tissue, a non-significant decline in renal tissue, and a significant reduction in cardiac tissue. The levels of GSH in hepatic and renal tissue were found to be non-significantly increased but significantly increased in cardiac tissue compared to controls. GR activity was found to be considerably decreased in the treated group. G-S-T levels increased significantly in all treated group. Etoposide injections caused a non-significant change in the GPX level of hepatic tissue, whereas renal and cardiac tissues showed a significant increase. The activity of CAT in hepatic tissue was significantly increased, while CAT activity in renal tissue showed a non-significant decrease, whereas in cardiac tissue, significantly lower levels were observed than in control group. The level of CYTp450 in hepatic and cardiac tissues showed a significant increase; however, renal tissue showed non-significant depletion, whereas CYTb5 in hepatic, renal, and cardiac tissues was significantly lower than controls. The protein content in the hepatic tissue was not significantly increased, whereas the total protein in the renal and cardiac tissues was increased significantly. The research finding is indicative of detoxification activity in the etoposide model.


El etopósido es un agente antimitótico y antineoplásico eficaz que se utiliza para tratar diversas neoplasias malignas humanas. En el presente estudio, se inyectó etopósido por vía intraperitoneal a las ratas a razón de 1 mg/kg/día durante 52 días (52 dosis). Los animales control recibieron solución salina fisiológica (0,5 ml) por vía intraperitoneal diariamente por 52 dosis. El peso corporal de las ratas tratadas con etopósido se redujo significativamente en comparación con las ratas del grupo control. La peroxidación lipídica demostró un aumento insignificante del tejido hepático, una disminución no significativa del tejido renal y una reducción significativa del tejido cardíaco. Se encontró que los niveles de GSH en el tejido hepático y renal no aumentaron significativamente, pero sí aumentaron significativamente en el tejido cardíaco en comparación con los controles. Se encontró que la actividad de GR disminuyó considerablemente en el grupo tratado. Los niveles de G-S-T aumentaron significativamente en todos los grupos tratados. Las inyecciones de etopósido provocaron un cambio no significativo en el nivel de GPX del tejido hepático, mientras que los tejidos renal y cardíaco mostraron un aumento significativo. La actividad de CAT en el tejido hepático aumentó significativamente, mientras que la actividad de CAT en el tejido renal mostró una disminución no significativa, mientras que en el tejido cardíaco se observaron niveles significativamente más bajos que en el grupo de control. El nivel de CYTp450 en los tejidos hepático y cardíaco mostró un aumento significativo; sin embargo, el tejido renal mostró un agotamiento no significativo, mientras que CYTb5 en los tejidos hepático, renal y cardíaco fue significativamente menor que los controles. El contenido de proteínas en el tejido hepático no aumentó significativamente, mientras que la proteína total en los tejidos renal y cardíaco aumentó significativamente. El hallazgo de la investigación es indicativo de la actividad de desintoxicación en el modelo de etopósido.


Asunto(s)
Animales , Masculino , Ratas , Etopósido/administración & dosificación , Corazón/efectos de los fármacos , Riñón/efectos de los fármacos , Hígado/efectos de los fármacos , Antioxidantes/administración & dosificación , Tamaño de los Órganos/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Peroxidación de Lípido , Citocromos b5/análisis , Ratas Wistar , Sistema Enzimático del Citocromo P-450/análisis , Etopósido/farmacología , Riñón/ultraestructura , Hígado/ultraestructura , Microscopía , Miocardio/ultraestructura , Antineoplásicos Fitogénicos , Antioxidantes/farmacología
20.
J Ethnopharmacol ; 331: 118301, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-38735419

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Many ethnopharmacological properties (anti-tumor, etc.) have been credited to Plectranthus esculentus tuber but the scientific basis has not been established. AIM OF THE STUDY: To evaluate the effect of methanol extract of P. esculentus tuber (MEPET) (phase 1) and its fractions (phase 2) on benign prostatic hyperplasia (BPH) in rats. MATERIALS AND METHODS: The study was conducted in two phases. Phase 1, thirty-five male albino rats (6 weeks old) were divided into seven groups of five rats each: normal control (NC) received olive oil (subcutaneously) and water (orally); disease control (DC) received testosterone propionate (TP) (3 mg/kg) and water; test groups (1,2,3 and 4) received TP + MEPET at 100, 200, 400, 600 mg/kg respectively; positive control, received TP + finasteride (5 mg/70 kg). After 28 days, their relative prostate weights (RPW) and prostate specific antigen (PSA) were determined. Phase 2, thirty rats were divided into 6 groups of 5 rats each: NC received olive oil (subcutaneously daily) and dimethyl sulfoxide (DMSO) (orally); DC received TP (3 mg/kg), and DMSO; test group 1 received TP and aqueous fraction of MEPET (400 mg/kg); test group 2 received TP and methanol fraction of MEPET (400 mg/kg); test group 3 received TP, and ethyl acetate fraction of MEPET (400 mg/kg); positive control received TP and finasteride (5 mg/70 kg). After 28 days, their erythrocyte sedimentation rates, RPW, prostate levels of PSA, DHT, inflammatory, apoptotic markers and prostate histology were determined. RESULTS: Ethyl acetate fraction of MEPET modulated most of the parameters of BPH in the rats in a manner akin to finasteride as corroborated by prostate histology. CONCLUSIONS: EFPET could be useful in the treatment of BPH.


Asunto(s)
Metanol , Extractos Vegetales , Plectranthus , Hiperplasia Prostática , Ratas Wistar , Animales , Masculino , Hiperplasia Prostática/tratamiento farmacológico , Hiperplasia Prostática/patología , Hiperplasia Prostática/inducido químicamente , Extractos Vegetales/farmacología , Metanol/química , Plectranthus/química , Ratas , Próstata/efectos de los fármacos , Próstata/patología , Antígeno Prostático Específico/sangre , Tubérculos de la Planta , Tamaño de los Órganos/efectos de los fármacos , Solventes/química , Propionato de Testosterona
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