Long-term ethanol consumption promotes hepatic tumorigenesis but impairs normal hepatocyte proliferation in rats

Chronic and excessive alcohol consumption has been related to an increased risk of several cancers, including that of the liver; however, studies in animal models have yet to conclusively determine whether ethanol acts as a tumor promoter in hepatic tumorigenesis. We examined whether prolonged alcohol consumption could act as a hepatic tumor promoter after initiation by diethylnitrosamine (DEN) in a rat model. Male Sprague-Dawley rats were injected with 20 mg DEN/kg body weight 1 wk before introduction of either an ethanol liquid diet or an isoenergic control liquid diet. Hepatic pathological lesions, hepatocyte proliferation, apoptosis, PPARα and PPARγ, and plasma insulin-like growth factor 1 (IGF-1) levels were assessed after 6 and 10 mo. Mean body and liver weights, plasma IGF-1 concentration, hepatic expressions of proliferating cellular nuclear antigen and Ki-67, and cyclin D1 in ethanol-fed rats were all significantly lower after 10 mo of treatment compared with control rats. In addition, levels of hepatic PPARγ protein, not PPARα, were significantly higher in the ethanol-fed rats after prolonged treatment. Although ethanol feeding also resulted in significantly fewer altered hepatic foci, hepatocellular adenoma was detected in ethanol-fed rats at 10 mo, but not in control rats given the same dose of DEN. Together, these results indicate that chronic, excessive ethanol consumption impairs normal hepatocyte proliferation, which is associated with reduced IGF-1 levels, but promotes hepatic carcinogenesis. © 2011 American Society for Nutrition.

Heat shock protein production and immunity and altered fetal development in diabetic pregnant rats

We evaluated associations between the concentrations of heat shock proteins (hsp60 and hsp70) and their respective antibodies, alterations in maternal reproductive performance, and fetal malformations in pregnant rats with hyperglycemia. Mild diabetes (MD) or severe diabetes (SD) was induced in Sprague-Dawley rats prior to mating; non-treated non-diabetic rats (ND) served as controls. On day 21 of pregnancy, maternal blood was analyzed for hsp60 and hsp70 and their antibodies; and fetuses were weighed and analyzed for congenital malformations. Hsp and anti-hsp levels were correlated with blood glucose levels during gestation. There was a positive correlation between hsp60 and hsp70 levels and the total number of malformations (R∈=∈0.5908, P∈=∈0.0024; R∈=∈0.4877, P∈=∈0.0134, respectively) and the number of malformations per fetus (R∈=∈0.6103, P∈=∈0.0015; R∈=∈0.4875, P∈=∈0.0134, respectively). The anti-hsp60 IgG concentration was correlated with the number of malformations per fetus (R∈=∈0.3887, P∈=∈0.0451) and the anti-hsp70 IgG level correlated with the total number of malformations (R∈=∈0.3999, P∈=∈0.0387). Moreover, both hsp and anti-hsp antibodies showed negative correlations with fetal weight. The results suggest that there is a relationship between hsp60 and hsp70 levels and their respective antibodies and alterations in maternal reproductive performance and impaired fetal development and growth in pregnancies associated with diabetes. © 2012 Cell Stress Society International.

The renin-angiotensin system plays a major role in voiding dysfunction of ovariectomized rats

Aims: The renin-angiotensin system (RAS) plays a major role in cardiovascular diseases in postmenopausal women, but little is known about its importance to lower urinary tract symptoms. In this study we have used the model of ovariectomized (OVX) estrogen-deficient rats to investigate the role of RAS in functional and molecular alterations in the urethra and bladder. Main methods: Responses to contractile and relaxant agents in isolated urethra and bladder, as well as cystometry were evaluated in 4-month OVX Sprague-Dawley rats. Angiotensin-converting enzyme activity and Western blotting for AT1/AT2 receptors were examined. Key findings: Cystometric evaluations in OVX rats showed increases in basal pressure, capacity and micturition frequency, as well as decreased voiding pressure. Angiotensin II and phenylephrine produced greater urethral contractions in OVX compared with Sham group. Carbachol-induced bladder contractions were significantly reduced in OVX group. Relaxations of urethra and bladder to sodium nitroprusside and BAY 41-2272 were unaffected by OVX. Angiotensin-converting enzyme activity was 2.6-fold greater (p < 0.05) in urethral tissue of OVX group, whereas enzyme activity in plasma and bladder remained unchanged. Expressions of AT1 and AT2 receptors in the urethra were markedly higher in OVX group. In bladder, AT1 receptors were not detected, whereas AT2 receptor expression was unchanged between groups. 17β-Estradiol replacement (0.1 mg/kg, weekly) or losartan (30 mg/kg/day) largely attenuated most of the alterations seen in OVX group. Significance: Prolonged estrogen deprivation leads to voiding dysfunction and urethral hypercontractility that are associated with increased ACE activity and up-regulation of angiotensin AT1/AT2 receptor in the urethral tissue. © 2013 Elsevier Inc. All rights reserved.

Exposição à dieta ocidental durante a gestação, lactação, fase juvenil e susceptibilidade à carcinogênese química do cólon em ratos adultos da linhagem Sprague-Dawley

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Efeitos da toxina botulínica do tipo A isolada ou em associação com a finasterida sobre a próstata do cão e rato Sprague-Dawley

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Carcinogênese de mama em modelo experimental de exposição gestacional, juvenil e adulta ao herbicida Diuron [3(3,4-Diclorofenil)1,1, Dimetil uréia] em fêmeas Sprague-Dawley

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Exposição in utero ao desregulador endócrino Bisfenol A e à Genisteína: efeitos sobre a morfogênese e a susceptibilidade a carcinogênese prostática em ratos Sprague-Dawley

Pós-graduação em Patologia - FMB

Indole-3-carbinol attenuates the deleterious gestational effects of bisphenol A exposure on the prostate gland of male F1 rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Maternal Western Style Diet Increases Susceptibility to Chemically-Induced Mammary Carcinogenesis in Female Rats Offspring

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Efeitos da exposição gestacional ao Bisfenol-A, a Genisteína e ao Indol-3-Carbinol sobre morfogênese e carcinogênese de órgãos reprodutores de fêmeas Sprague-Dawley da geração F1

A exposição in utero a xenoestrógenos pode aumentar o risco de neoplasias de natureza endócrina na vida adulta. O Bisfenol A (BPA), componente de resinas e plástico, considerado xenoestrógeno e desregulador endócrino, tem sido investigado pelos seus potenciais efeitos adversos para a saúde humana. Como a Genisteína e o Indol-3-Carbinol possuem propriedades que podem inibir neoplasias de natureza endócrina, é possível que também atuem modulando/modificando os efeitos causados pela exposição gestacional ao BPA. O presente projeto teve como objetivos: (1) Avaliar os efeitos da exposição gestacional ao Bisfenol - A (BPA) sobre a morfogênese do útero e ovários na prole de fêmeas Sprague-Dawley (SD) da geração F1; (2) Avaliar se a exposição gestacional a genisteína e ao indol-3-carbinol altera os efeitos do BPA sobre sobre a morfogênese do útero e ovários na geração F1 e (3) avaliar os efeitos da exposição ao BPA, e às associações BPA e genisteína, BPA e indol-3-carbinol em relação à susceptibilidade a carcinogênese induzida pela N-Metil-N-Nitrosuréia (MNU). Portanto, fêmeas prenhas da linhagem SD foram divididas em 7 grupos experimentais e expostas ao Bisfenol A (BPA) (25 ou 250 ug/kg p.c.) DG 10 até o DG 21 (Moral et al. 2008), além de ração basal ou ração contendo genisteína (250 mg/kg) ou indol-3-carbinol (2000 mg/kg) durante toda a gestação. Parte da prole Fêmeas SD foi sacrificada parte no Dia Pós-Natal (DPN) 21 e parte ao final da 25ª semana após iniciação ou não com a MNU. Ao DPN 21 os ovários e útero foram removidos para contagem de folículos e morfometria, respectivamente. A prole restante de fêmeas recebeu uma única dose de MNU (50 mg/kg) ou solução de NaCl (1 ml/kg) no DPN 51 e foi sacrificada na 25ª semana após a aplicação de MNU ou de NaCl. Ovários e útero foi removidos para análises histológicas, incluindo a determinação de lesões proliferativas ...

The effects of high doses of nandrolone decanoate and exercise on prostate microvasculature of adult and older rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Aggravation of nonalcoholic steatohepatitis by moderate alcohol consumption is associated with decreased SIRT1 activity in rats

Chronic alcohol intake decreases adiponectin and sirtuin 1 (SIRT1) expressions, both of which have been implicated in various biological processes including inflammation, apoptosis and metabolism. We have previously shown that moderate consumption of alcohol aggravates liver inflammation and apoptosis in rats with pre-existing nonalcoholic steatohepatitis (NASH). This study investigated whether moderate alcohol intake alters SIRT1 activity, adiponectin/Adiponectin receptor (AdipoR)-related signaling and lipid metabolism in a pre-existing NASH status. Sprague-Dawley rats were fed with a high-fat diet (71% energy from fat) for 6 weeks to induce NASH then subsequently divided into 2 sub-groups: fed either a modified high-fat diet (HFD, 55% energy from fat) or a modified high-fat alcoholic diet (HFA, 55% energy from fat and 16% energy from ethanol) for an additional 4 weeks. We observed in comparison to HFD group, HFA increased hepatic nuclear SIRT1 protein but decreased its deacetylase activity. SREBP-1c protein expression and FAS mRNA levels were significantly upregulated, while DGAT1/2 and CPT-I mRNA levels were downregulated in the livers of HFA compared to HFD. Although hepatic AdipoR1 decreased, HFA did not alter AdipoR2 and their downstream signaling. There were no significant changes in plasma adiponectin and free fatty acids (FFA), as well as adiponectin expression in adipose tissue between the two groups. The present study indicates that suppression in SIRT1 deacetylase activity contributes to alcohol-exacerbated hepatic inflammation and apoptosis in rats with pre-existing NASH. In addition, moderate alcohol intake did not modulate adiponectin/AdipoR signaling axis in this model.

Three-dimensional aspects of the lingual papillae and their connective tissue cores in the tongue of rats: a scanning electron microscope study

The aim of the present study was to describe the tridimensional morphological characteristics of the lingual papillae and their connective tissue cores (CTCs) in Sprague Dawley rats. Four types of papillae were reported on the dorsal surface. Filiform papillae were distributed on the tongue surface and after epithelial maceration a conic and multifilamentary shape of the CTCs was revealed. Fungiform papillae were reported on the rostral and middle regions covered by a squamous epithelium. After the removal of the epithelium, the shape of a volcano with the taste orifice at its top was noted. Foliate papillae were composed of five pairs of epithelial folds situated on the lateral-caudal margin of the tongue. After the removal of the epithelium, they were shown to be limited by thin laminar projections. The vallate papilla with an oval shape was present in the caudal region and delimited by an incomplete groove. The morphological characteristics of the lingual papillae of Sprague Dowley rats, three-dimensional SEM images, and the types of papillae on the dorsal surface were similar to those reported previously in other rodent mammals. The maceration technique revealed the details of extracellular matrix with varied shapes form of connective tissue cores.

Transcorneal Electrical Stimulation Shows Neuroprotective Effects in Retinas of Light-Exposed Rats

PURPOSE. To examine the effects of transcorneal electrical stimulation (TES) on retinal degeneration of light-exposed rats. METHODS. Thirty-three Sprague Dawley albino rats were divided into three groups: STIM (n = 15) received 60 minutes of TES, whereas SHAM (n = 15) received identical sham stimulation 2 hours before exposure to bright light with 16,000 lux; healthy animals (n = 3) served as controls for histology. At baseline and weekly for 3 consecutive weeks, dark-and light-adapted electroretinography was used to assess retinal function. Analysis of the response versus luminance function retrieved the parameters Vmax (saturation amplitude) and k (luminance to reach 1/2Vmax). Retinal morphology was assessed by histology (hematoxylin-eosin [HE] staining; TUNEL assay) and immunohistochemistry (rhodopsin staining). RESULTS. Vmax was higher in the STIM group compared with SHAM 1 week after light damage (mean intra-individual difference between groups 116.06 mu V; P = 0.046). The b-wave implicit time for the rod response (0.01 cd.s/m(2)) was lower in the STIM group compared with the SHAM group 2 weeks after light damage (mean intra-individual difference between groups 5.78 ms; P = 0.023); no other significant differences were found. Histological analyses showed photoreceptor cell death (TUNEL and HE) in SHAM, most pronounced in the superior hemiretina. STIM showed complete outer nuclear layer thickness preservation, reduced photoreceptor cell death, and preserved outer segment length compared with SHAM (HE and rhodopsin). CONCLUSIONS. This sham-controlled study shows that TES can protect retinal cells against mild light-induced degeneration in Sprague Dawley rats. These findings could help to establish TES as a treatment in human forms of retinal degenerative disease. (Invest Ophthalmol Vis Sci. 2012;53:5552-5561) DOI: 10.1167/iovs.12-10037

Increasing Intensity of TENS Prevents Analgesic Tolerance in Rats

Transcutaneous electrical nerve stimulation (TENS) reduces hyperalgesia and pain. Both low-frequency (LF) and high-frequency (HF) TENS, delivered at the same intensity (90% motor threshold [MT]) daily, result in analgesic tolerance with repeated use by the fifth day of treatment. The current study tested 1) whether increasing intensity by 10% per day prevents the development of tolerance to repeated TENS; and 2) whether lower intensity TENS (50% MT) produces an equivalent reduction in hyperalgesia when compared to 90% MT TENS. Sprague-Dawley rats with unilateral knee joint inflammation (3% carrageenan) were separated according to the intensity of TENS used: sham, 50% LF, 50% HF, 90% LF, 90% HF, and increased intensity by 10% per day (IF and HF). The reduced mechanical withdrawal threshold following the induction of inflammation was reversed by application of TENS applied at 90% MT intensity and increasing intensity for the first 4 days. On the fifth day, the groups that received 90% MT intensity showed tolerance. Nevertheless, the group that received an increased intensity on each day still showed a reversal of the mechanical withdrawal threshold with TENS. These results show that the development of tolerance can be delayed by increasing intensity of TENS. Perspective: Our results showed that increasing intensity in both frequencies of TENS was able to prevent analgesic tolerance. Results from this study suggest that increasing intensities could be a clinical method to prevent analgesic tolerance and contribute to the effective use of TENS in reducing inflammatory pain and future clinical trials. (c) 2012 by the American Pain Society