BrdU does not induce hepatocellular damage in experimental Wistar rats.

Bromodeoxyuridine (BrdU) is used in studies related to cell proliferation and neurogenesis. The multiple intraperitoneal injections of this molecule could favor liver function profile changes. In this study, we evaluate the systemic and hepatocellular impact of BrdU in male adult Wistar rats in 30 %-partial hepatectomy (PHx) model. The rats received BrdU 50 mg/Kg by intraperitoneal injection at 0.5, 1, 2, 3, 6, 9 and 16 days after 30 %-PH. The rats were distributed into four groups as follows, control, sham, PHx/BrdU(-) and PHx/BrdU(+). On day 16, we evaluated hepatocellular nuclei and analyzed histopathological features by haematoxylin-eosin stain and apoptotic profile was qualified by caspase-3 presence. The systemic effect was evaluated by liver markers such as alanine transferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), alkaline phosphatase (AP), bilirubin, total proteins and serum albumin content. The statistical analysis consisted of a student t-test and one-way ANOVA. BrdU did not induce apoptosis or hepatocellular damage in male rats. Multiple administrations of BrdU in male rats did not induce significant decrease body weight, but increased serum ALT and LDH levels were found. Our results show that the BrdU does not produce hepatocellular damage.

Aloe vera and copaiba oleoresin-loaded chitosan films for wound dressings: microbial permeation, cytotoxicity, and in vivo proof of concept.

Chitosan films are commonly used for wound dressing, provided that this polymer has healing, mucoadhesiveness and antimicrobial properties. These properties can be further reinforced by the combination of chitosan with polysaccharides and glycoproteins present in aloe vera, together with copaiba oleoresin's pharmacological activity attributed to sesquiterpenes. In this work, we developed chitosan films containing either aloe vera, copaiba oil or both, by casting technique, and evaluated their microbial permeation, antimicrobial activity, cytotoxicity, and in vivo healing potential in female adult rats. None of the developed chitosan films promoted microbial permeation, while the cytotoxicity in Balb/c 3 T3 clone A31 cell line revealed no toxicity of films produced with 2 % of chitosan and up to 1 % of aloe vera and copaiba oleoresin. Films obtained with either 0.5 % chitosan or 0.5 % copaiba oleoresin induced cell proliferation which anticipate their potential for closure of wound and for the healing process. The in vivo results confirmed that tested films (0.5 % copaiba-loaded chitosan film and 0.5 % aloe vera-loaded chitosan film) were superior to a commercial dressing film. For all tested groups, a fully formed epithelium was seen, while neoformation of vessels seemed to be greater in formulations-treated groups than those treated with the control. Our work confirms the added value of combining chitosan with aloe vera and copaiba oil in the healing process of wounds.

Type 1 Corticotropin-Releasing Factor Receptor Differentially Modulates Neurotransmitter Levels in the Nucleus Accumbens of Juvenile versus Adult Rats.

Adversity is particularly pernicious in early life, increasing the likelihood of developing psychiatric disorders in adulthood. Juvenile and adult rats exposed to social isolation show differences in anxiety-like behaviors and significant changes in dopamine (DA) neurotransmission in the nucleus accumbens (NAc). Brain response to stress is partly mediated by the corticotropin-releasing factor (CRF) system, composed of CRF and its two main receptors, CRF-R1 and CRF-R2. In the NAc shell of adult rats, CRF induces anxiety-like behavior and changes local DA balance. However, the role of CRF receptors in the control of neurotransmission in the NAc is not fully understood, nor is it known whether there are differences between life stages. Our previous data showed that infusion of a CRF-R1 antagonist into the NAc of juvenile rats increased DA levels in response to a depolarizing stimulus and decreased basal glutamate levels. To extend this analysis, we now evaluated the effect of a CRF-R1 antagonist infusion in the NAc of adult rats. Here, we describe that the opposite occurred in the NAc of adult compared to juvenile rats. Infusion of a CRF-R1 antagonist decreased DA and increased glutamate levels in response to a depolarizing stimulus. Furthermore, basal levels of DA, glutamate, and γ-Aminobutyric acid (GABA) were similar in juvenile animals compared to adults. CRF-R1 protein levels and localization were not different in juvenile compared to adult rats. Interestingly, we observed differences in the signaling pathways of CRF-R1 in the NAc of juveniles compared to adult rats. We propose that the function of CRF-R1 receptors is differentially modulated in the NAc according to life stage.

Chronic early-life stress increases cognitive impulsivity and D2 immunoreactivity in the nucleus accumbens of adult rats.

Chronic early life stress (ECS) induced by limited bedding and nesting (LBN) material in rodents is a naturalistic stress model that mimics many of the behavioral and neural consequences of child abuse and neglect; however, the effect of ECS on adult impulsivity has never been studied. The aim of our work was to determine the effects of ECS on cognitive impulsivity and its relation to D2 immunoreactivity in the nucleus accumbens (NAc) and prefrontal cortex (PFC) of adult male rats. Sprague-Dawley rats were exposed to LBN from postnatal day 2 to 9. We evaluated dams' maternal behavior and offspring corticosterone levels. The rats' impulsive cognitive behavior was evaluated by a delay-discounting task (transitional bridge) on P70, and we evaluated D2 receptors by immunostaining. Our results indicated that ECS affected maternal behavior in the dams and increased pups' corticosterone levels at P9, but not in adults. ECS rats showed lower frequencies of choosing the delayed reinforcer and shorter latencies to cross on the delay-discounting task. In addition, ECS rats showed increased D2 immunoreactivity in the NAc when compared with controls. Our data suggest that ECS can cause impulsive behaviors in adult rats characterized by less convenient choices, likely related to an increase in D2 receptors in the NAc. These findings could contribute to our understanding of the effects of child abuse and neglect on impulsive behavior.

Effects of escalating versus fixed ethanol exposure on ∆FosB expression in the mesocorticolimbic pathway in adolescent and adult rats.

Background: We have reported induction of ∆FosB in adolescent rats that drank less ethanol than adults yet exhibited a progressive increase in ethanol intake.Objective: To test the hypothesis that an escalating pattern of ethanol exposure is more effective to induce ∆FosB expression [at prelimbic cortex (PrL), nucleus accumbens core and shell, striatum, basolateral amygdala (BLA) and central amygdala (CeC)] than a pattern equated for number of exposures yet employing a fixed ethanol dose.Methods: Adolescent and adult (Exp. 1, n = 48) male and female (n = 24 of each sex) or only adult male (Exp. 2, n = 36) Wistar rats were intermittently intubated with vehicle, escalating (from 0.5 to 2.5 g/kg) or fixed (2.0 g/kg) doses of ethanol, across 18 sessions. ∆FosB induction was assessed using immunohistochemistry. Ethanol intake, anxiety and risk-taking were assessed (in adults only) via two-bottles tests and the multivariate concentric square field.Results: Both patterns heightened ∆FosB levels similarly in adolescents and adults and in males and females. Fixed dosing induced ∆FosB in all areas (p < .05) except the CeC, whereas the escalating pattern induced ∆FosB in the PrL and BLA only (p < .05). Ethanol intake was initially lower in ethanol pre-exposed subjects than in control subjects (p < .05). Rats exposed to the fixed pattern exhibited enhanced risk-taking behavior (p < .05).Conclusions: The results agree with studies showing ethanol-mediated induction of ∆FosB in reward areas and indicate that, following ethanol intubations, this induction is similar in adolescents and adults. The induction of ∆FosB seems not necessarily associated with susceptibility for ethanol intake.

Characterization of fiber types in different muscles of the hindlimb in female weanling and adult Wistar rats.

We analyzed lesser diameter and distribution of fiber types in different skeletal muscles from female Wistar rats using a histoenzymology Myofibrillar Adenosine Tri-phosphatase (mATPase) method. Fragments from muscles were frozen and processed by mATPase in different pH. Adult and weanling rat soleus muscles presented a predominance of type I fibers and larger fiber diameters. In the plantar muscle in adult rats, the type IIB fibers demonstrated greater lesser diameter while in the weanling animals, types I and IIB fibers were larger. The plantar muscle of animals of both ages was composed predominantly of the type IID fibers. The type IID fibers were observed in similar amounts in the lateral gastrocnemius and the medial gastrocnemius muscles. Type IIB fibers showed predominance and presented higher size in comparison with other types in the EDL muscle. The present study shows that data on fiber type distribution and fiber lesser diameter obtained in adult animals cannot always be applied to weanling animals of the same species. Using the mATPase, despite the difficult handling, is an important tool to determine the different characteristics of the specific fibers in the skeletal muscle tissue.

Análise morfométrica da parede intestinal do íleo de ratos submetidos a intensa carência de proteínas / Análisis morfométrica de la pared intestinal del íleo de ratas sometidos a intensacarencia de proteínas / Morphometrics analysis of the intestinal wall of the ileum of rats submitted to intensive lack of protein

Neste trabalho foram utilizados seis animais (Rattus norvegicus com 90 dias de idade) divididos em dois grupos: GC (grupo controle) e GE (grupo experimental). Os animais do GC receberam ração com teor protéico de 26% e os do GE ração com 4% de proteínas. Após 90 dias de experimento, os animais foram submetidos à eutanásia, à retirada do íleo e a processos histológicos corados por Hematoxilina e Eosina (HE), quando se avaliaram os efeitos da desnutrição protéica severa (4%) sobre ratos Wistar adultos (Rattus norvegicus) nos seguintes parâmetros: peso corporal; parede total do íleo; túnica mucosa; túnica muscular; altura do enterócito; diâmetro maior nuclear. A análise histomorfométrica da parede total do íleo dos ratos adultos desnutridos evidenciou que houve uma redução estatisticamente significante no grupo experimental em relação ao grupo controle. Ou seja: a parede intestinal alterou-se como um todo, especialmente na espessura da túnica mucosa, muscular, altura do enterócito e diâmetro maior de seu núcleo, permitindo-se concluir que a desnutrição protéica afeta tecidos de alta e baixa renovação celular presente no íleo(AU)

Six animals (Rattus norvegicus - 90 days of age) were divided into two groups: CG (Control Group) and EG (Experimental Group) were used in this study. The animals in the CG received 26%-protein chow and the EG received 4%- protein chow. 90 days later, the animals were submitted to euthanasia, remotion of their ileum for histological processes, and Hematoxylin and Eosin staining (HE). The effects of severe protein undernutrition (4%) on Wistar rats (Rattus norvegicus) regarding the following parameters were assessed: body weight, total wall thickness of the ileum, tunica mucosa, muscle tunic, enterocyte height, and higher nuclear diameter. The histomorphometric analysis of the total wall of the ileum of undernourished adult rats evidenced that there was a statistically significant reduction for the experimental group in relation to the control group. The intestinal wall suffered atrophy demonstrating that protein undernourishment affected all the tissues at the ileum(AU)

En esta investigación fueron utilizados seis animales (Rattus norvegicus con 90 días de edad) divididos en dos grupos: GC (grupo control) y GE (Grupo experimental). Los animales del GC recibieron ración con contenido proteico de 26% y los del GE ración con 4% de proteínas. Tras 90 días de experimento los animales fueron sometidos a eutanasia, remoción del íleo, procesos histológicos corados por Hematoxilina y Eosina (HE). Cuando se evaluaron los efectos de la desnutrición proteica severa (4%) sobre las ratas Wistar adultas (Rattus norvegicus) en los siguientes parámetros: peso corporal, pared total del íleo, túnica mucosa, túnica muscular, altura del enterocito y diámetro mayor nuclear. El análisis histomorfométrica de la pared total del íleo de las ratas adultas desnutridas evidenció que hubo una reducción estadísticamente significante em el grupo experimental en relación al grupo control. O sea: la pared intestinal se alteró como un todo, especialmente en La espesura de la túnica mucosa, muscular, altura del enterocito y diámetro mayor de su núcleo, permitiéndose concluir que La desnutrición proteica afecta tejidos de alta y baja renovación celular presente en el íleo(AU)

Análise morfométrica da parede intestinal do íleo de ratos submetidos a intensa carência de proteínas / Análisis morfométrica de la pared intestinal del íleo de ratas sometidos a intensacarencia de proteínas / Morphometrics analysis of the intestinal wall of the ileum of rats submitted to intensive lack of protein

Neste trabalho foram utilizados seis animais (Rattus norvegicus com 90 dias de idade) divididos em dois grupos: GC (grupo controle) e GE (grupo experimental). Os animais do GC receberam ração com teor protéico de 26% e os do GE ração com 4% de proteínas. Após 90 dias de experimento, os animais foram submetidos à eutanásia, à retirada do íleo e a processos histológicos corados por Hematoxilina e Eosina (HE), quando se avaliaram os efeitos da desnutrição protéica severa (4%) sobre ratos Wistar adultos (Rattus norvegicus) nos seguintes parâmetros: peso corporal; parede total do íleo; túnica mucosa; túnica muscular; altura do enterócito; diâmetro maior nuclear. A análise histomorfométrica da parede total do íleo dos ratos adultos desnutridos evidenciou que houve uma redução estatisticamente significante no grupo experimental em relação ao grupo controle. Ou seja: a parede intestinal alterou-se como um todo, especialmente na espessura da túnica mucosa, muscular, altura do enterócito e diâmetro maior de seu núcleo, permitindo-se concluir que a desnutrição protéica afeta tecidos de alta e baixa renovação celular presente no íleo

Six animals (Rattus norvegicus - 90 days of age) were divided into two groups: CG (Control Group) and EG (Experimental Group) were used in this study. The animals in the CG received 26%-protein chow and the EG received 4%- protein chow. 90 days later, the animals were submitted to euthanasia, remotion of their ileum for histological processes, and Hematoxylin and Eosin staining (HE). The effects of severe protein undernutrition (4%) on Wistar rats (Rattus norvegicus) regarding the following parameters were assessed: body weight, total wall thickness of the ileum, tunica mucosa, muscle tunic, enterocyte height, and higher nuclear diameter. The histomorphometric analysis of the total wall of the ileum of undernourished adult rats evidenced that there was a statistically significant reduction for the experimental group in relation to the control group. The intestinal wall suffered atrophy demonstrating that protein undernourishment affected all the tissues at the ileum

En esta investigación fueron utilizados seis animales (Rattus norvegicus con 90 días de edad) divididos en dos grupos: GC (grupo control) y GE (Grupo experimental). Los animales del GC recibieron ración con contenido proteico de 26% y los del GE ración con 4% de proteínas. Tras 90 días de experimento los animales fueron sometidos a eutanasia, remoción del íleo, procesos histológicos corados por Hematoxilina y Eosina (HE). Cuando se evaluaron los efectos de la desnutrición proteica severa (4%) sobre las ratas Wistar adultas (Rattus norvegicus) en los siguientes parámetros: peso corporal, pared total del íleo, túnica mucosa, túnica muscular, altura del enterocito y diámetro mayor nuclear. El análisis histomorfométrica de la pared total del íleo de las ratas adultas desnutridas evidenció que hubo una reducción estadísticamente significante em el grupo experimental en relación al grupo control. O sea: la pared intestinal se alteró como un todo, especialmente en La espesura de la túnica mucosa, muscular, altura del enterocito y diámetro mayor de su núcleo, permitiéndose concluir que La desnutrición proteica afecta tejidos de alta y baja renovación celular presente en el íleo