Effects of Gundelia tournefortii L. on biochemical parameters, antioxidant activities and DNA damage in a rat model of experimental obesity / Efeitos de Gundelia tournefortii L. em parâmetros bioquímicos, atividades antioxidantes e danos ao DNA em um modelo de obesidade experimental de rato

The present study was designed to investigate the effects of Gundelia tournefortii L. plant extract on different tissues in terms of DNA damage, biochemical and antioxidant parameter values in rats with high-calorie diets. With this aim, Wistar albino male rats were divided into 4 groups containing 6 rats each and the study was completed over 12 weeks duration. At the end of the implementation process over the 12 weeks, rats were sacrificed and blood and tissue samples were obtained. Analyses were performed on blood and tissue samples. According to results for DNA damage (8-OHdG), in brain tissue the OG2 group was significantly reduced compared to the NC group. For MDA results in liver tissue, OG1 and OG2 groups were determined to increase by a significant degree compared to the control group, while the OG2 group was also increased significantly compared to the obese group. In terms of the other parameters, comparison between the groups linked to consumption of a high calorie diet (HCD) and administration of Gundelia tournefortii L. in terms of antioxidant activities and serum samples obtained statistically significant results. Gundelia tournefortii L. plant extracts had effects that may be counted as positive on antioxidant parameter activity and were especially identified to improve DNA damage and MDA levels in brain tissues. Additionally, consumption of Gundelia tournefortii L. plant extract in the diet may have antiobesity effects; thus, it should be evaluated for use as an effective weight-loss method and as a new therapeutic agent targeting obesity.

O presente estudo foi desenhado para investigar os efeitos do extrato da planta Gundelia tournefortii L. em diferentes tecidos em termos de danos ao DNA, valores de parâmetros bioquímicos e antioxidantes em ratos com dietas hipercalóricas. Com esse objetivo, ratos Wistar albinos machos foram divididos em 4 grupos contendo 6 ratos cada e o estudo foi concluído ao longo de 12 semanas de duração. No final desse processo de implementação, os ratos foram sacrificados e amostras de sangue e tecido foram obtidas. As análises foram realizadas em amostras de sangue e tecido. De acordo com os resultados para danos ao DNA (8-OHdG), no tecido cerebral o grupo OG2 foi significativamente reduzido em comparação com o grupo NC. Para os resultados de MDA no tecido hepático, os grupos OG1 e OG2 aumentaram significativamente em comparação ao grupo controle, enquanto o grupo OG2 também aumentou significativamente em comparação ao grupo obeso. Quanto aos demais parâmetros, a comparação entre os grupos ligados ao consumo de dieta hipercalórica (DC) e à administração de Gundelia tournefortii L. em termos de atividades antioxidantes e amostras de soro obteve resultados estatisticamente significativos. Os extratos de plantas de Gundelia tournefortii L. tiveram efeitos que podem ser considerados positivos na atividade dos parâmetros antioxidantes e foram especialmente identificados para melhorar os danos ao DNA e os níveis de MDA nos tecidos cerebrais. Além disso, o consumo de extrato vegetal de Gundelia tournefortii L. na dieta pode ter efeitos antiobesidade; portanto, deve ser avaliado para uso como um método eficaz de perda de peso e como um novo agente terapêutico voltado para a obesidade.

Anthelmintic activity of nanoencapsulated carvacryl acetate against gastrointestinal nematodes of sheep and its toxicity in rodents / Atividade anti-helmíntica do acetato de carvacrila nanoencapsulado sobre nematoides gastrintestinais de ovinos e toxicidade em roedores

Abstract The objective of this study was to evaluate the efficacy of carvacryl acetate (CVA) and nanoencapsulated CVA (nCVA) on gastrointestinal nematodes of sheep. The CVA was nanoencapsulated with chitosan/gum arabic and the efficacy of nanoencapsulation (EE), yield, zeta potential, nanoparticle morphology and release kinetics at pH 3 and 8 were analyzed. Acute and subchronic toxicity were evaluated in rodents and reduction of egg counts in the faeces (FECRT) of sheep. The sheep were divided into four groups (n = 10): G1, 250 mg/kg CVA; G2, 250 mg/kg nCVA; G3, polymer matrix and G4: 2.5 mg/kg monepantel. EE and nCVA yield were 65% and 57%, respectively. The morphology of the nanoparticles was spherical, size (810.6±286.7 nm), zeta potential in pH 3.2 (+18.3 mV) and the 50% release of CVA at pHs 3 and 8 occurred at 200 and 10 h, respectively. nCVA showed LD50 of 2,609 mg/kg. CVA, nCVA and monepantel reduced the number of eggs per gram of faeces (epg) by 57.7%, 51.1% and 97.7%, respectively. The epg of sheep treated with CVA and nCVA did not differ from the negative control (P>0.05). Nanoencapsulation reduced the toxicity of CVA; however, nCVA and CVA presented similar results in the FECRT.

Resumo O objetivo deste trabalho foi avaliar a eficácia do acetato de carvacrila (ACV) e do ACV nanoencapsulado (nACV) sobre nematóides gastrintestinais de ovinos. O ACV foi nanoencapsulado com quitosana/goma arábica e foi analisada a eficácia de nanoencapsulamento (EE), o rendimento, potencial zeta, morfologia das nanopartículas e cinética de liberação em pH 3 e 8. Foram avaliadas as toxicidades aguda e subcrônica em roedores e a redução da contagem de ovos nas fezes (RCOF) de ovinos. Os ovinos foram divididos em quatro grupos (n = 10): G1, 250 mg/kg ACV; G2, 250 mg/kg de nACV; G3, matriz polimérica e G4: 2,5 mg/kg de monepantel. A EE e o rendimento de nACV foram de 65% e 57%, respectivamente. A morfologia das nanopartículas foi esférica, tamanho (810,6±286,7 nm), potencial zeta no pH 3,2 (+18,3 mV) e a liberação de 50% de CVA nos pHs 3 e 8 ocorreu às 200 e 10 h, respectivamente. nACV apresentou DL50 de 2.609 mg/kg. ACV, nACV e o monepantel reduziram a contagem de ovos por grama de fezes (opg) em 57,7%, 51,1% e 97,7%, respectivamente. A contagem de opg de ovelhas tratadas com ACV e nCVA não diferiu do controle negativo (P>0,05). O nanoencapsulamento reduziu a toxicidade do AVC; no entanto, nACV e ACV apresentaram resultados semelhantes na RCOF.

Physiological changes of growth hormone during lactation in pup rats artificially reared.

During the lactation period, rat pups are fed by the dam, and the patterns of mother-pup interaction change during this period. Additionally, there are changes in feeding; first, mother´s milk is the only food needed for sustenance, and later, it is combined with solid food and water. GH serum concentrations depend on both maternal-pup interaction and energy metabolism. In the artificial rearing (AR) procedure, pups are deprived of mother-pup interaction, and the feeding pattern is controlled. This rearing paradigm has been used in rats to analyze the effects of maternal deprivation on social behavior. In the present study, we analyzed the variation in GH, acylated ghrelin and IGF-1 serum concentrations throughout the lactation period in AR pups. At pnd7, the maternal rearing (MR) pups responded to a 4 h fast with a drop in GH serum concentration, which is a well-known response to maternal deprivation. GH serum levels in the AR pups did not change, suggesting an adaptation phenomenon. A dopamine inhibitory effect of GH secretion was observed in pnd7 cultured somatotropes, suggesting dopamine regulation of GH secretion at this age. Acylated ghrelin serum levels in the AR pups showed an inverted pattern compared to that in the MR pups, which was related to the artificial feeding pattern. IGF-1 serum levels were lower in the AR pups than in MR pups, which was associated with hepatic GH resistance and with low Igf1 mRNA expression at pnd7. Interestingly, at pnd14, both pup groups showed high hepatic Igf1 mRNA expression but low IGF-1 serum levels, and this was inverted at pnd21. However, serum glucose levels were lower in the AR pups at pnd14 but reached the same levels as the MR pups at pnd21. Moreover, hepatomegaly and higher hepatic GH-receptor levels were observed in the AR pups at pnd21, which was in agreement with an absence of a solid food meal. During AR, the pups lost the maternal interaction-stimulated GH secretion, which correlated with lower IGF-1 serum levels during the first week of postnatal development. Later, the AR pups exhibited hepatic responses, in order to satisfy the metabolic demand for the normal weaning, with low carbohydrates levels in their meal.

Effects of Moderate- and High-Intensity Chronic Exercise on the Adiponectin Levels in Slow-Twitch and Fast-Twitch Muscles in Rats.

Background and objectives: Adipose tissue and skeletal muscle secrete adiponectin, a hormone abundantly secreted by adipocytes, that through the adiponectin receptor, regulate glucose and lipid metabolism. Adiponectin appears to protect skeletal muscles from inflammatory damage induced by oxidative stress. It has been suggested that decreased adiponectin levels could be associated with pathologic conditions, including obesity and diabetes. Furthermore, some studies suggest that exercise could have a beneficial effect by increasing adiponectin levels, but this observation remains controversial. It is also unknown if physical exercise modifies adiponectin expression in skeletal muscles. The aim of this study was to investigate the effect of chronic exercise on serum adiponectin and adiponectin expression in slow-twitch (soleus) and fast-twitch (plantaris) muscles in healthy rats. Materials and methods: Two-month-old male Wistar rats were randomly divided into three groups with n = 6 in each group: control (C), moderate-intensity training (MIT), and high-intensity training (HIT). The rats were conditioned to run on a treadmill for the 8-week period. Forty-eight hours after the last session, blood samples were collected for adiponectin measurements and total RNA was isolated from plantaris and soleus muscles to measure by RT-qPCR adiponectin receptor 1 and adiponectin mRNA expression level. Results: MIT and HIT groups had reduced adiponectin protein levels in serum and the plantaris muscle, but not changes in adiponectin protein were observed in the soleus muscle. No significant differences in Adiponectin receptor 1 (AdipoR1) gene expression were observed following intense or moderate exercise in either muscle group studied. Conclusions: Our study shows that decreasing levels of circulating adiponectin is a result of physical exercise and should not be generalized as a predictive marker of disease.

Bioavailability of Different Vitamin D Oral Supplements in Laboratory Animal Model.

Background and Objectives: The major cause of vitamin D deficiency is inadequate exposure to sunlight. It is difficult to supplement it with food because sufficient concentrations of vitamin D naturally occur only in a handful of food products. Thereby, deficiency of this vitamin is commonly corrected with oral supplements. Different supplement delivery systems for improved vitamin D stability and bioavailability are proposed. In this study, we compared efficiency of three vitamin D delivery systems: microencapsulated, micellized, and oil-based. Materials and Methods: As a model in this medical testing, laboratory rats were used for the evaluation of bioavailability of different vitamin D vehicles. Animals were divided into three groups: the first one was given microencapsulated vitamin D3, the second-oil-based vitamin D3, and the third-micellized vitamin D3. Test substances were given per os to each animal for 7 days, and vitamin D concentration in a form of 25-hydroxyvitamin D (25(OH)D) in the blood was checked both during the vitamin delivery period and later, up to the 24th day. Results: Comparison of all three tested products showed that the microencapsulated and oil-based vitamin D3 vehicles were the most bioavailable in comparison to micellized vitamin D3. Even more, the effect of the microencapsulated form of vitamin D3 remained constant for the longest period (up to 14 days). Conclusions: The results of this study suggest that the oral vitamin D supplement vehicle has an impact on its bioavailability, thus it is important to take into account how much of the suppled vitamin D will be absorbed. To maximize the full exploit of supplement, the best delivery strategy should be employed. In our study, the microencapsulated form of vitamin D was the most bioavailable.

Healing potential of zerumbone ointment on experimental full-thickness excision cutaneous wounds in rat.

Zerumbone is a monocyclic sesquiterpene compound. Based on report, it is the predominant bioactive compound from the rhizomes of Zingiber zerumbet. The study was undertaken to evaluate the therapeutic effects of topical zerumbone on excision wounds in rats. A 1% (w/w) simple ointment containing zerumbone was applied topically (100 mg ointment per rat) once a day on full-thickness excision wounds created on rats. The wound tissue was removed and used for estimation of antioxidant activity and to observe histopathological changes. Immunohistochemical staining was performed to study the expression pattern of vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-ß1 and collagen IV. Zerumbone exhibited antimicrobial activity against Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Candida albicans and Candida tropicali. Zerumbone ointment has potent wound healing capacity as evident from the wound contraction on 15th post wounding day. The histopathological examinations of healed wound sections showed greater tissue regeneration, more fibroblasts and angiogenesis in zerumbone ointment-treated group. VEGF, TGF-ß1 and collagen IV expression were also correlative with the healing pattern observed. Zerumbone possesses potent antioxidant activity by increasing superoxide dismutase, catalase, glutathione and decreased lipid peroxidation. The synergistic effects of both antimicrobial and antioxidant activities in zerumbone are deduced to have accelerated the wound repair. The results demonstrate that zerumbone possessed strong wound healing potential and can be exploited to accelerate excision wound healing.

Plasma Ghrelin Concentrations Were Altered with Oestrous Cycle Stage and Increasing Age in Reproductively Competent Wistar Females.

Changes in appetite occur during the ovarian cycle in female mammals. Research on appetite-regulatory gastrointestinal peptides in females is limited, because reproductive changes in steroid hormones present additional experimental factors to control for. This study aimed to explore possible changes in the orexigenic (appetite-stimulating) gastrointestinal peptide hormone ghrelin during the rodent oestrous cycle. Fed and fasted plasma and stomach tissue samples were taken from female Wistar rats (32-44 weeks of age) at each stage of the oestrous cycle for total ghrelin quantification using radioimmunoassay. Sampling occurred during the dark phase when most eating takes place in rats. Statistical analysis was by paired-samples t-test, one-way ANOVA on normally distributed data, with Tukey post-hoc tests, or Kruskal-Wallis if not. GLM univariate analysis was used to assess main effects and interactions in ghrelin concentrations in the fed or fasted state and during different stages of the ovarian cycle, with age as a covariate. No consistent fed to fasted ghrelin increases were measured in matched plasma samples from the same animals, contrary to expectations. Total ghrelin concentrations did not significantly change between cycle stages with ANOVA, in either fed or fasted plasma or in stomach tissue. This was despite significantly decreased fasted stomach contents at oestrus (P = 0.028), suggesting decreased food intake. There was however a significant interaction in ghrelin plasma concentrations between fed and fasted proestrus rats and a direct effect of age with rats over 37 weeks old having lower circulating concentrations of ghrelin in both fed and fasted states. The biological implications of altered ghrelin plasma concentrations from 37 weeks of age are as yet unknown, but warrant further investigation. Exploring peripheral ghrelin regulatory factor changes with increasing age in reproductively competent females may bring to light potential effects on offspring development and nutritional metabolic programming.

The effect of multivitamin-multimineral supplementation on the health status of inbred Wistar and spontaneously hypertensive rat strains.

The nutraceutical industry has proliferated in recent years, with the most popular form of supplementation being the multivitamin-multimineral (MVMM) supplement. In the animal health sector, supplement use has also expanded. The objective of this study was to determine the effects of MVMM supplementation, beneficial or otherwise, on the general health status of the spontaneously hypertensive rat (SHR) strain, an animal model used in hypertension research. A commercially prepared MVMM supplement was given tri-weekly via oral dosing for 8 weeks to two groups of seven adult female SHR and Wistar rats. Their corresponding control groups were dosed with deionised water only. Systolic and diastolic blood pressure, fasting blood glucose, growth rate and food and water intake were measured weekly. At the end of 8 weeks, the animals were euthanased and a full blood profile, urine sodium to potassium ratio, blood urea nitrogen levels and total plasma cholesterol was measured for all groups. The results indicated that growth rate was higher for the SHR supplemented group. Supplementation also decreased diastolic blood pressure in both Wistar and SHR groups and increased red blood cell count and decreased total cholesterol in the SHR group. No adverse effects on the general health status of the animals were observed. MVMM supplementation may therefore be useful in aiding growth and delaying the onset of hypertension and its effects. It may also assist in the longevity of the breeding stock of SHR rats.

Determining the effect of storage conditions on prothrombin time, activated partial thromboplastin time and fibrinogen concentration in rat plasma samples.

Coagulation parameters are usually included in clinical and preclinical safety studies to evaluate the effect of xenobiotics on the extrinsic or intrinsic pathways of coagulation. The analysis is generally performed at the time of terminal sacrifice where many activities are scheduled. Chances of delay in analysis are likely particularly when blood is collected for coagulation via the abdominal vena cava. This experiment was planned to assess the variations in coagulation parameters caused by delay in analysis as well as by storage conditions. Blood was collected from the posterior vena cava under isoflurane anesthesia, and the plasma was separated immediately. Coagulation parameters were evaluated at 0, 6, 24 and 48 h from the plasma stored at room temperature, as well as plasma stored under refrigerated and freezing conditions. Stability of the analytes in blood was also evaluated under refrigerated conditions for 6 h. All parameters were analyzed using a semi-automated coagulometer. Prothrombin time (PT) was stable under all three storage conditions for up to 6 h. Although statistically significant differences were observed for activated partial thromboplastin time (APTT) at room and refrigeration temperatures for up to 6 h, the difference was clinically non-relevant. Fibrinogen was found to be the most stable parameter that showed consistency in results even up to 48 h under all three storage conditions. Plasma for PT can be stored and analyzed without any significant changes for up to 6 h from the actual blood collection, while fibrinogen level testing can be extended for up to 48 h after collection under any storage condition. For reliable APTT results, plasma samples should be run immediately after collection.

Efecto de la administración subcrónica de glucosamina oral en la regulación del peso corporal, glucemia y dislipidemias provocada por una dieta hipercalórica en rata Wistar / Effect of subchronic oral administration of glucosamine in the regulation of body weight, glycemia and dyslipidemia induced hypercholesterolemic Wistar rat

Objetivo: Este estudio evaluó el efecto de la glucosamina oral en el sobrepeso y dislipidemia provocada por una dieta hipercalórica en ratas. Métodos: En 4 grupos de ratas Wistar: alimentados con dieta comercial para roedores y agua de beber sin grupo de control y con glucosamina (500 mg/kg-1 por día) grupo glucosamina y con dieta hipercalórica enriquecida al 24% (g/g) compuesta por manteca de cerdo y agua de beber sin grupo hipercalórico y con glucosamina grupo hipercalórico + grupo glucosamina, durante 22 semanas, se evaluaron el peso corporal, grasa abdominal, niveles de glucemia, triglicéridos, colesterol total y lipoproteínas de alta densidad en suero. Resultados: Se observó un aumento del peso corporal y glucemia en suero con dislipidemias en el grupo con dieta hipercalórica grupo hipercalórico versus grupo de controle (p<0.001); al administrarse glucosamina para esta misma dieta grupo hipercalórico + grupo glucosamina se minimizaron los efectos presentados, disminuyendo la cantidad de grasa abdominal y los niveles del perfil lípido en suero (p>0.05) y regulándose el peso corporal, las lipoproteínas de alta densidad y la glucemia basal (p<0.05). Conclusion: La glucosamina reguló el peso corporal y la glucemia en sangre y minimizó las dislipidemias provocadas por la dieta hipercalórica, favoreciendo el aumento de colesterol lipoproteínas de ...

Objective: This study evaluated the effect of oral glucosamine on overweight and dyslipidemia caused by a high-fat diet in rats. Methods: Four groups of Wistar rats: fed with commercial rodent food and drinking water without (control group) and with glucosamine (500 mg kg-1 per day) and a high-fat diet enriched with 24% (g/g) butter pork and drinking water without and with glucosamine, for 22 weeks; the body weight, abdominal fat, blood glucose, triglycerides, total cholesterol, and high density lipoprotein in serum were evaluated. Results: Body weight gain, increased blood glucose levels and dyslipidemia were observed in the high-fat diet group versus the control group (p<0.001). When glucosamine was administered the same diet the effects were minimized, with a decrease in the amount of abdominal-fat and lipid profile levels in serum (p>0.05), regulated body weight, and high density lipoprotein and glycaemia (p<0.05). The glucosamine did not affect body weight and lipid metabolism in rats when administered with a normal diet. Conclusions: Glucosamine regulated the body weight blood glucose and dyslipidemia caused by a high-fat diet, favoring increased high density lipoprotein cholesterol in rats. It did not affect body weight and lipid metabolism when administered with commercial food. .

Effect of repeated freezing and thawing on 18 clinical chemistry analytes in rat serum.

In a preclinical research laboratory, using serum samples that have been frozen and thawed repeatedly is sometimes unavoidable when needing to confirm previous results or perform additional analysis. Here we determined the effects of multiple cycles of refrigeration or freezing and thawing of rat serum at 3 temperature conditions for different storage times on clinical chemistry analytes. Serum samples obtained from adult Wistar rats were stored at 2 to 8 °C and -10 to -20 °C for as long as 72 h and at -70 °C for as long as 30 d. At different time points (24, 48, and 72 h for samples stored at 2 to 8 °C or -10 to -20 °C and 1, 7, and 30 d for samples stored at -70 °C), the samples were brought to room temperature, analyzed, and then stored again at the designated temperature. The results obtained after each storage cycle were compared with those obtained from the initial analysis of fresh samples. Of the 18 serum analytes evaluated, 14 were stable without significant changes, even after 3 freeze-thaw cycles at the tested temperature ranges. Results from this study will help researchers working with rat serum to interpret the biochemical data obtained from serum samples that have been frozen and thawed repeatedly.

Differences in hematologic variables in rats of the same strain but different origin.

BACKGROUND: Wistar rats are frequently used in toxicologic studies; however, the impact of animal source on hematologic reference intervals (RI) is not known. OBJECTIVE: The purpose of this study was to compare hematologic data of Wistar rats obtained from 2 breeders and to calculate preliminary RI for the Sysmex XT-2000iV hematology analyzer. METHODS: Blood collected in EDTA from 75 10-13-week-old rats (male, n = 38; female, n = 37) from breeder 1 and 60 rats (male, n = 30; female, n = 30) from breeder 2 was analyzed using a Sysmex XT-2000iV hematology analyzer. Results were analyzed for differences using a t-test or Mann-Whitney U-test. Sex-specific 95% RI were calculated for rats from both breeders. RESULTS: Significant breeder-specific differences were found for WBC, RBC, platelet, lymphocyte, monocyte, eosinophil, and reticulocyte counts and MCV, MCH, MPV, and plateletcrit for both sexes, and for HCT and hemoglobin concentration for female rats. The greatest differences (P < .0001) between rats from breeders 1 and 2, respectively, were found for WBC (female: 2.2-5.9 × 10(9) /L vs 4.2-9.4 × 10(9) /L 38; male: 3.4-9.5 vs 6.4-14.4 × 10(9) /L), lymphocyte (female: 1.7-4.8 × 10(9) /L vs 3.4-8.2 × 10(9) /L; male: 2.6-7.8 vs 5.2-12.4 × 10(9) /L), and platelet (female: 591-836 × 10(9) /L vs 804-1282 × 10(9) /L; male: 573-998 × 10(9) /L vs 861-1247 × 10(9) /L) counts. CONCLUSION: Differences in hematologic RI between Wistar rats obtained from different breeders underscore the need to evaluate untreated control animals for comparison, rather than using historical RI, to detect compound-related effects in preclinical safety studies. Valid RI for control animals are needed and should be verified when using a new supplier to avoid misinterpretation of data. Low reference limits for some variables, such as WBC counts, in rats from one source may preclude their use in studies in which detection of leukopenia is required.

Modulation of RAGE isoforms expression in the brain and plasma of rats exposed to transient focal cerebral ischemia.

Activation of RAGE (receptor for advanced glycation endproducts) and of its subtypes may play a role in neuronal damage and neuroinflammation associated with brain ischemia, though the underlying mechanisms remain unclear. In this study, we have examined by Western blotting the expression of RAGE isoforms in the cerebral cortex and striatum of Wistar rats subjected to transient (1 or 2 h) middle cerebral artery occlusion (tMCAo). The findings show that the full-length RAGE (~50 kDa) and its isoforms in the 26-43 kDa range are significantly decreased in the ischemic cortex, but not in the striatum, after 1 and 2 h tMCAo when compared to the sham group. By contrast, in the striatum, ischemia-reperfusion injury caused a significant increase of full-length RAGE and its isoforms in the 72-100 kDa range. We also investigated the soluble form of RAGE, which was significantly decreased in the plasma of rats subjected to transient or permanent MCAo. In conclusion, the present data demonstrate that regional brain expression of RAGE is differentially affected by tMCAo in rat. These modifications are accompanied by a decrease in the plasma levels of soluble RAGE, thereby suggesting a potential role for soluble RAGE as a peripheral biomarker of focal ischemia.

A study of brain and serum brain-derived neurotrophic factor protein in Wistar and Wistar-Kyoto rat strains after electroconvulsive stimulus.

BACKGROUND: Serum brain-derived neurotrophic factor (BDNF) protein has been related to depression and less consistently to its treatments in human studies. However, animal studies have failed to demonstrate a clear link between BDNF protein in serum and brain tissue. METHODS: Serum and brain tissue levels of BDNF protein were measured with ELISA in the Wistar-Kyoto (WKY) and Wistar strains at 1 and 7 days after 5 daily electroconvulsive stimulus sessions or sham treatments. RESULTS: The WKY strain showed lower baseline serum BDNF protein relative to Wistar controls. After 5 electroconvulsive stimuli, BDNF protein density was significantly increased in hippocampus and cortical regions, but not in the cerebellum or in serum. A clear correlation between brain and serum BDNF was not observed in either strain or treatment group. DISCUSSION: Despite lower baseline serum BDNF protein in the WKY strain, a lack of change in serum BDNF after electroconvulsive stimulus and a lack of correlation between brain and serum BDNF protein calls into question the relevance of serum BDNF as a measure of depression and treatment response.

Absorption levels and morphological features of fetal organs in wistar rats treated with lead acetate / Niveles de absorción y características morfológicas de los órganos fetales en ratas wistar tratadas con acetato de plomo

Lead is one of the heavy metals most used in industry. Poisoning due to long-term lead exposure is known as saturnism, and is an occupational illness that has been known for many years. Lead is highly toxic and can compromise the structural and functional patterns of organs and systems. The aim of this study was to examine the lungs and kidneys of fetuses from female Wistar rats exposed to lead acetate. In this study, the lungs and kidneys of 20 fetuses from female rats that had previously been treated with lead acetate were dissected, fixed, embedded in paraffin and stained with hematoxylin and eosin. Macroscopic changes to the shape, color and consistency of organs from fetuses treated with this heavy metal were observed, in comparison with organs from control fetuses. Microscopic lesions characterized by vascular sclerosis, cell atrophy or hyperplasia, progressive interstitial fibrosis, inclusion bodies containing lead acetate and glomerular sclerosis were found in the kidneys. The lesions found in the lungs consisted of destructuring of the parenchyma, impregnation with lead acetate, formation of fibrosis, extravasation of vascular fluids, reduction of the alveolar spaces and formation of alveolar edema. These changes were correlated with the level of lead acetate absorption, as determined using atomic spectrophotometry.

El plomo es un metal pesado utilizado en la industria. El envenenamiento debido a la exposición prolongada por plomo es una enfermedad profesional conocida por muchos años. La toxicidad del plomo es muy expresiva y puede poner en peligro el modelo estructural y funcional de los órganos y sistemas. El objetivo de este estudio fue examinar los pulmones y riñones de fetos de ratas Wistar expuestos al acetato de plomo. En este estudio, 20 fetos de ratas Wistar previamente tratados con acetato de plomo durante la gestación, tuvieron sus órganos disecados, fijados, incluidos en parafina y teñidos con hematoxilina y eosina. Macroscópicamente, los órganos fetales tratados por este metal fueron comparados con los órganos de fetos controles en relación a forma, color y consistencia. Microscópicamente, se encontraron lesiones en el riñón que se caracterizaron por esclerosis vascular, atrofia o hiperplasia de células, fibrosis intersticial progresiva, presencia de cuerpos de inclusión que contenían acetato de plomo y esclerosis glomerular. En el pulmón se observó desorganización del parénquima impregnado con acetato de plomo, formación de fibrosis, líquido intersticial, reducción de los espacios alveolares y edema alveolar. Estos cambios se correlacionaron con el nivel de absorción de acetato de plomo, determinado por espectrometría atómica.

Diabetes-induced prefrontal nissl substance deficit and the effects of neem-bitter leaf extract treatment / Diabetes inducida por déficit prefrontal de sustancia de nissl y el efecto del tratamiento con extracto de hoja de neem amargo

Cognitive dysfunction is reportedly associated with poorly-managed diabetes mellitus. In this study, we report the effect of oral treatment with combined leaf extract (CLE) of neem and bitter leaf on the prefrontal cortex of diabetic Wistar rats. Adult male Wistar rats were randomized to one of the following groups: control, diabetic (STZ-induced), STZ + CLE, STZ + metformin and CLE only. At euthanasia, paraffin sections of the prefrontal cortex were stained with cresyl fast violet; while malondialdehyde (MDA) and glutathione peroxidase (GPx) were assayed in prefrontal homogenates. Oral CLE produced normoglycemia in the treated hyperglycaemic rats. Besides, Nissl-stained prefrontal sections showed no morphologic deficits in all the groups except the untreated diabetic rats. In the latter, there was weak Nissl staining, while prefrontal MDA was significantly high at euthanasia, compared with the control and CLE-treated rats (P<0.05). This study showed that untreated diabetes mellitus is associated with prefrontal Nissl body deficit and oxidative stress in Wistar rats. The absence of these deficits in CLE-treated rats suggests a neuroprotective effect of the extract in streptozotocin-induced diabetic rats. This may improve the cognitive function of the prefrontal cortex in diabetes mellitus.

La disfunción cognitiva es presuntamente asociada con un mal manejo de la diabetes mellitus. En este estudio, se presenta el efecto del tratamiento oral combinado con extracto de hoja (CLE) de hoja de neem amarga sobre la corteza prefrontal de ratas Wistar con diabetes. Las ratas Wistar adultas fueron asignadas al azar a uno de los siguientes grupos: control, diabetes (STZ inducida), STZ + CLE, STZ + metformina y CLE. Después de la eutanasia, los cortes de parafina de la corteza prefrontal se tiñeron con violeta de cresil rápido, mientras que el malondialdehído (MDA) y la glutatión peroxidasa (GPx) fueron analizadas en homogenizados prefrontales. El CLE produce normoglucemia en las ratas hiperglucémicas tratadas. Además, las secciones prefrontales teñidas para Nissl no muestran ningún déficit morfológico en todos los grupos excepto en las ratas diabéticas sin tratamiento. En este último caso, hubo una tinción de Nissl débil, mientras que la MDA prefrontal fue significativamente más alta en comparación con los grupos de ratas control y las tratadas con CLE (p <0,05). Este estudio mostró que la diabetes mellitus no tratada se asocia con déficit prefrontal de cuerpos de Nissl y estrés oxidativo en ratas Wistar. La ausencia de estos déficits en las ratas tratadas CLE, sugiere un efecto neuroprotector del extracto en ratas diabéticas inducidas por estreptozotocina. Esto puede mejorar la función cognitiva de la corteza prefrontal en la diabetes mellitus.

Ultrastructural changes in the kidney cortex of rats treated with lead acetate / Cambios ultraestructurales en la corteza renal de ratas tratadas con acetato de plomo

The purpose of this study was to investigate the ultrastructural effects of lead on the kidney cortex of rats. Wistar Albino rats (180-200g body weight) were divided into a controlled and lead acetate-exposed group. Rats received lead acetate at 500 ppm in their drinking water for 60 days. Both groups were fed with the same standard food, but lead acetate was added to the drinking water. During the experimental period, blood samples were taken from the abdominal aorta of the anesthetised animals. At the end of exposure, body weight and blood lead levels were measured. The kidney tissue samples were prepared and analyzed by light and transmission electron microscopy. Cortical renal tubules show various degenerative changes with focal tubular necrosis invaded by inflammatory cells. The ultrastructural alterations found in lead acetate-treated rats were a diminution in the amount of filtration slits, increased fusion of foot processes in epithelial cells of the glomeruli, increase of lysosomal structures and pinocytic vesicles as well as large mitochondria in proximal tubule cells.

El propósito de este estudio fue investigar los efectos ultraestructurales del plomo en la corteza renal. Ratas Wistar albinas (180-200g de peso corporal) fueron divididas en grupo control y grupo experimental. Las ratas recibieron 500 ppm de acetato de plomo en el agua potable durante 60 días. Ambos grupos fueron alimentados con el mismo alimento estándar, pero acetato de plomo se le añadió al agua potable al grupo experimental. Durante el período experimental, se tomaron bajo anestesia muestras sanguíneas desde la parte abdominal de la aorta. Al final de la exposición, fueron medidos el peso corporal y los niveles de plomo en la sangre. Fueron preparadas las muestras de tejido renal y se analizaron mediante microscopía de luz y electrónica de transmisión. Los túbulos renales corticales mostraron varios cambios degenerativos con necrosis tubular focal invadida por células inflamatorias. Las alteraciones ultraestructurales encontradas en las ratas tratadas con acetato de plomo correspondieron a una disminución en la cantidad de ranuras de filtración, aumento de la fusión de los procesos podales en las células epiteliales de los glomérulos, aumento de la estructura lisosomal y las vesículas pinocíticas, así como grandes mitocondrias en las células del túbulo proximal.

Baseline serum cardiac troponin I concentrations in Sprague-Dawley, spontaneous hypertensive, Wistar, Wistar-Kyoto, and Fisher rats as determined with an ultrasensitive immunoassay.

Cardiac troponins have proved to be reliable blood biomarkers for identifying a variety of myocardial alterations in humans and animals. Recently, an ultrasensitive cTnI assay (Erenna IA) has been used to demonstrate increases in baseline cTnI resulting from drug-induced myocardial injury in rats, dogs, and monkeys, as well as to document baseline cTnI ranges in Sprague-Dawley (SD) rats. The present study was initiated to use the Erenna cTnI assay to further document baseline cTnI concentrations in normal control animals from multiple strains, including SD, Spontaneous Hypertensive (SHR), Wistar, Wistar-Kyoto (WKY), and Fisher strains. Baseline cTnI concentrations were quantified in all rats tested, and males had higher mean cTnI concentrations than females of the same strain. SHR males had the highest mean cTnI concentrations and the largest cTnI variability. Interestingly, cTnI concentrations increased in castrated SHR compared with unaltered male SHR, whereas cTnI concentrations decreased in ovariectomized SHR compared with unaltered female SHR. These results show significant differences in cTnI concentrations between strains, sexes, and noncardiac surgical alterations in control animals, and identify these as potential contributing factors to cTnI baseline variability that should be taken into account when using ultrasensitive cTnI as a biomarker to assess preclinical cardiotoxicity.

Avaliações hematológicas e bioquímicas do uso de diclofenaco de sódio, meloxicam e firocoxibe em ratos / Evaluations hematological and biochemical by the use of sodium diclofenac, meloxicam and firocoxib in rats

O presente trabalho avaliou os parâmetros hematológicos e bioquímicos do uso de diclofenaco de sódio, meloxicam e firocoxibe em ratos Wistar. Os ratos foram distribuídos em grupos: G1 (controle), G2 (diclofenaco de sódio: 15 mg/kg), G3 (meloxicam: 2,0 mg/ kg), G4 (meloxicam: 10,0 mg/ kg), G5 (firocoxibe: 5,0 mg/ kg) e G6 (firocoxibe: 25,0 mg/ kg). Os fármacos foram administrados por via intragástrica (gavage) a cada 24 horas, durante cinco dias e avaliados em três momentos: M1 (48 horas após o início do tratamento), M2 (96 horas após o início do tratamento) e M3 (72 horas após o término do tratamento). Em cada momento de cada grupo, foram avaliados de cinco a sete animais e realizados os exames laboratoriais. Não foram observadas alterações significativas nos parâmetros bioquímicos e hematológicos com o uso de meloxicam e firocoxibe. O diclofenaco de sódio produziu alterações no eritrograma (redução de hemácias, hematócrito e na taxa de hemoglobina) durante o tratamento e não alterou a contagem das plaquetas e leucometria, com exceção dos basófilos. Não produziu alterações nas atividades de AST, FA, GGT, ureia, creatinina, sódio e potássio. Entretanto, causou diminuições das proteínas plasmática e total sérica, albumina e globulina. Conclui-se que o diclofenaco de sódio não produz grandes alterações no hemograma e exames bioquímicos, enquanto que, o meloxicame o firocoxibe não produzem alterações e efeitos deletérios dose-dependentes nestes exames laboratoriais.

This work has evaluated the hematological and biochemical profile by the use of sodium diclofenac, meloxicam and firocoxib in Wistar rats. The rats were distributed in groups: G1 (control), G2 (diclofenac sodium: 15 mg/kg), G3 (meloxicam: 2.0 mg/ kg), G4 (meloxicam: 10.0 mg/ kg), G5 (firocoxib: 5.0 mg/ kg) e G6 (firocoxib: 25.0 mg/ kg). The drugs were administered intragastrically (gavage) once a day, during five days and evaluated in three moments: M1 (48 hours after the beginning of the treatment), M2 (96 hours after the beginning of the treatment) and M3 (72 hours after the ending of the treatment). In each moment of each group, five to seven animals were evaluated and laboratory exams were performed. There were no significant changes observed in the biochemical and hematological parameters by the use of meloxicam and firocoxib. One of the effects of the sodium diclofenac was eritrogram variation as hematocrit, erythrocytes, hemoglobin decrease during the treatment. In addition, the platelets and total white blood cells counts did not change except for basophil. There was no changes in AST, ALP, GGT, urea, creatinine, sodium, potassium values. However, the values of protein, globulin and albumin decreased. It was concluded that diclofenac sodium does not provide large variations in the hemogram and biochemical profile than the meloxicam and firocoxib do not provide delletery effects in laboratories tests.