The influence of physical exercise on oestrogen and androgen receptor expression in a chemically and hormonally-induced rat model of prostate cancer

Background: Oestrogen (ER) and androgen (AR) recep- tors play an important role in normal prostate development and are also implied in prostate cancer (PCa) development. Several studies suggested that physical activity may decrease the risk of PCa development and also changes sexual hor- mones and their receptors. This study aimed to evaluate the effects of physical exercise on ERα and AR expression in a rat model of chemically and hormonally-induced PCa. Materials and Methods: Fifty-five male Wistar Unilever rats of 12 weeks of age were randomly divided into four groups: control sedentary (n = 10), control exercised (n = 10), induced sedentary (n = 15) and induced exercised (n = 20). Animals from exercised groups started the exercise training in a treadmill (Treadmill Control LE 8710, Harvard Apparatus, USA), at the age of 8 weeks, for 35 weeks (5 days/week). The protocol for PCa induction started at 12 weeks of age and consisted of sequential administration of flutamide (50 mg/kg, TCI Chemicals), testosterone propion- ate (100 mg/kg, TCI Chemicals) and N-methyl-N-nitrosourea (30 mg/kg, Isopac®, Sigma Chemical Co.), followed by sub- cutaneous implants of crystalline testosterone. Animals were sacrificed at 61 weeks of age and a complete necropsy was performed. All experiments were approved by DGAV (no. 021326). Antibodies for Erα (1:500, clone 6F11, Novocastra) and AR (clone PG21, Merck Millipore) were used for the immunohistochemical study. The staining extension was evaluated in normal prostate tissue and in dorsolateral pros- tate lesions (hyperplasia, dysplasia, prostatic intraepithelial neoplasia (PIN) and microinvasive carcinoma) and assessed to five levels (0%, 75%), con- sidering the extension of immunopositive tissue. Data was analysed with SPSS 25.Results: The normal prostate tissue and dorsolateral prostate lesions of animals from all groups were immunopositive for Erα and AR. However, the groups showed high immunoposi- tivity for AR and low positivity for Erα ( 0.05). The malignant lesions (PIN and microinvasive carcinoma) showed lower AR expression when compared with normal prostate tissue in all groups. Conclusions: As expected, the AR expression was lower in malignant lesions. Inversely to that reported in other studies, the exercise training did not modify the ERα and AR expres- sion, which may be related to the duration and type of exer- cise performed

Effects of physical exercise in biochemical parameters and dorsolateral prostate lesions: data from a rat model of prostate cancer

Background: Prostate cancer (PCa) is among the most prevalent cancers worldwide. Physical exercise is widely recognized due to its beneficial effects. This study aimed to evaluate the effects of physical exercise on biochemical pa- rameters and in dorsolateral prostate lesions in a rat model of PCa. Materials and Methods: Ninety-five male Wistar Unilever rats were randomly divided into eight groups sacrificed at 35 (groups I) or 61 weeks of age (groups II): control sedentary groups (Cont+Sed I (n = 10); Cont+Sed II (n = 10)); induced sedentary group (PCa+Sed I (n = 10); PCa+Sed II (n = 15)); control exercised groups (Cont+EX I (n = 10); Cont+EX II (n = 10)) and induced exercised groups (PCa+EX I (n = 10); PCa+EX II (n = 20)). All procedures were approved (DGAV, no. 021326). Animals from exercised groups started the exer- cise program in a treadmill at 8 weeks of age, for 28 weeks or 53 weeks. The animals were trained 5 days/week, 60 min per day. Prostate lesions were induced at 12 weeks of age, with sequential administration of flutamide, testosterone propion- ate and N-methyl-N-nitrosourea, and subcutaneous implants of crystalline testosterone. Animals were sacrificed at 35 or 61 weeks of age. Peripheral blood of all animals was col- lected by intracardiac puncture. A complete necropsy was performed. The dorsolateral prostate tissues sections were processed for histological analysis. Data were analysed using SPSS 25. p 0.05). Dorsolateral prostate lesions were classified as dysplasia, prostatic intraep- ithelial neoplasia (PIN) and microinvasive carcinoma. The number of prostate lesions was higher in animals from groups II than in those from groups I, mainly in PCa+Sed II animals when compared with PCa+Sed I (p 0.05). Conclusions: Overall, the animals sacrificed at 61 weeks of age developed more dorsolateral prostate lesions than ani- mals sacrificed at 35 weeks of age, which may be related to a longer testosterone exposure

Pulegone and Eugenol Oral Supplementation in Laboratory Animals: Results from Acute and Chronic Studies

Essential oils are natural compounds used by humans for scientific purposes due to their wide range of properties. Eugenol is mostly present in clove oil, while pulegone is the main constituent of pennyroyal oil. To guarantee the safe use of eugenol and pulegone for both humans and animals, this study addressed, for the first time, the effects of these compounds, at low doses (chronic toxicity) and high doses (acute toxicity), in laboratory animals. Thirty-five FVB/n female mice were randomly assigned to seven groups (n = 5): group I (control, non-additive diet); group II (2.6 mg of eugenol + 2.6 mg of pulegone); group III (5.2 mg of eugenol + 5.2 mg of pulegone); group IV (7.8 mg of eugenol + 7.8 mg of pulegone); group V (7.8 mg of eugenol); group VI (7.8 mg of pulegone); and group VII (1000 mg of eugenol + 1000 mg of pulegone). The compounds were administered in the food. Groups I to VI were integrated into the chronic toxicity study, lasting 28 days, and group VII was used in the acute toxicity study, lasting 7 days. Animals were monitored to assess their general welfare. Water and food intake, as well as body weight, were recorded. On the 29th day, all animals were euthanized by an overdose of ketamine and xylazine, and a complete necropsy was performed. Blood samples were collected directly from the heart for microhematocrit and serum analysis, as well as for comet assay. Organs were collected, weighed, and fixed in formaldehyde for further histological analysis and enzymatic assay. Eugenol and pulegone induced behavioral changes in the animals, namely in the posture, hair appearance and grooming, and in mental status. These compounds also caused a decrease in the animals’ body weight, as well as in the food and water consumption. A mortality rate of 20% was registered in the acute toxicity group. Both compounds modulated the serum levels of triglycerides and alanine aminotransferase. Eugenol and pulegone induced genetic damage in all animals. Eugenol increased the activity of the CAT enzyme. Both compounds increased the GR enzyme at the highest dose. Moreover, pulegone administered as a single compound increased the activity of the GST enzyme. Histopathological analysis revealed inflammatory infiltrates in the lungs of groups II, III, and IV. The results suggest that eugenol and pulegone may exert beneficial or harmful effects, depending on the dose, and if applied alone or in combination

The red seaweed Grateloupia turuturu prevents epidermal dysplasia in HPV16-transgenic mice

Abstract: The role of dietary profiles in promoting or reducing the risk of multiple types of cancer is increasingly clear, driving the search for balanced foods and nutraceuticals. The red seaweed Grateloupia turuturu has been used as human food showing a balanced nutritional profile. This study aims to test in vivo chemopreventive effects of G. turuturu against cutaneous pre-malignant lesions in transgenic mice for the human papillomavirus type 16 (HPV16). Forty-four female HPV+/− or HPV−/− mice received a standard diet or were supplemented with 10% G. turuturu for 22 consecutive days. Cutaneous lesions (ear and chest skin) were identified histologically. Complementarily, the weights and histology of internal organs as well as blood biochemical and DNA integrity parameters were also assessed. G. turuturu consistently reduced the incidence of epidermal dysplasia induced by HPV16 on both cutaneous sites. Moreover, biochemical, DNA integrity and histological analyses confirmed G. turuturu edibility as no signs of toxicity were found. Dietary supplementation with G. turuturu is an effective and safe chemopreventive strategy in this model

An integrative approach to characterize the early phases of dimethylhydrazine-induced colorectal carcinogenesis in the rat

This study aimed to characterize an animal model of colorectal cancer (CRC) in the early stages of disease development. Twenty-nine male Wistar rats were divided into two control groups (CTRL1 and CTRL2), receiving EDTA–saline injections and two induced groups (CRC1 and CRC2), receiving 1,2-dimethylhydrazine (DMH) injections for seven consecutive weeks. CRC1 and CTRL1 were euthanized at the 11th week, while CRC2 and CTRL2 were euthanized at the 17th week. DMH treatment decreased microhematocrit values and IL-6, ghrelin, and myostatin serum levels. Histopathological analysis of intestinal sections showed that DMH-treated rats were characterized by moderate to severe epithelial dysplasia. An adenoma was observed in one animal (CRC2 group), and the presence of inflammatory infiltrate at the intestinal level was primarily observed in DMH-treated animals. DMH also induced Ki-67 immunoexpression. The gut microbiota analysis showed a higher abundance of Firmicutes, Clostridia, Clostridiales, Peptostreptococcaceae, Blautia, Romboutsia, and Clostridium sensu stricto in CRC than CTRL rats, whereas Prevotellaceae, Prevotella, Akkermansia, and Lactobacillus levels were more prevalent in CTRL animals. Our results suggest that this model could be helpful to investigate chemoprevention in the early stages of CRC

Asthma App Use and Interest Among Patients With Asthma: A Multicenter Study

info:eu-repo/semantics/publishedVersio

Dietary supplementation with chestnut (Castanea sativa) reduces abdominal adiposity in FVB/n mice: A preliminary study

The production of chestnut (Castanea sativa Miller) is mostly concentrated in Europe. Chestnut is recognized by its high content of antioxidants and phytosterols. This work aimed to evaluate the effects of dietary chestnut consumption over physiological variables of FVB/n mice. Eighteen FVB/n male 7-month-old mice were randomly divided into three experimental groups (n = 6): 1 (control group) fed a standard diet; 2 fed a diet supplemented with 0.55% (w/w) chestnut; and 3 supplemented with 1.1% (w/w) chestnut. Body weight, water, and food intake were recorded weekly. Following 35 days of supplementation, the mice were sacrificed for the collection of biological samples. Chestnut supplementation at 1.1% reduced abdominal adipose tissue. Lower serum cholesterol was also observed in animals supplemented with chestnut. There were no significant differences concerning the incidence of histological lesions nor in biochemical markers of hepatic damage and oxidative stress. These results suggest that chestnut supplementation may contribute to regulate adipose tissue deposition.This work is supported by National Funds by FCT - Portuguese Foundation for Science and Technology, under the project UIDB/04033/2020, CIMO (UIDB/00690/2020) and UIDB/CVT/00772/2020 Interreg Program for the financial support of the Project IBERPHENOL, Project Number 0377_IBERPHENOL_6_E; co-financed by European Regional Development Fund (ERDF) through POCTEP 2014-2020. This work was also supported by VALORIZEBYPRODUCTS Project, reference n.¿ 029152, funded by Portuguese Foundation for Science and Technology (FCT) and co-financed by the European Regional Development Fund (FEDER) through COMPETE 2020 - Operational Competitiveness and Internationalization Programme (POCI). This work was also financially supported by Project UID/EQU/00511/2019 - Laboratory for Process Engineering, Environment, Biotechnology and Energy – LEPABE funded by national funds through FCT/MCTES (PIDDAC) and Project “LEPABE-2-ECO-INNOVATION” – NORTE-01-0145-FEDER-000005, funded by Norte Portugal Regional Operational Programme (NORTE 2020), under PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), by the Research Centre of the Portuguese Institute of Oncology of Porto (CI-IPOP 37-2016) and by the Interact R&D project, operation number NORTE-01-0145-FEDER-000017, in its ISAC research line, co-financed by the ERDF through NORTE 2020. This work was also supported by PhD fellowship SFRH/BD/136747/2018