Continuous light reverts physical exercise effects on colon carcinogenesis induced by 1,2-dimethyl-hydrazine in rats

Colon cancer risk is reduced by appropriate levels of physical exercise. Light exposure during the night conveys endocrine changes on melatonin rhythm produced by pineal gland. This hormone is considered as a potent anti-oxidant with oncostatic properties. Both factors are related to colon cancer, which risk can be estimated by the evaluation of pre-malignant factors of colonic mucosa such as the Aberrant Crypt Foci (ACF). This study aims to verify whether the beneficial effects of physical exercise are related to the activity of the pineal gland. Thus, 40 rats were divided into 5 groups: G0, G1 and G2 were sedentary, G3 and G4 were submitted to a protocol of progressive swimming exercise for 10 weeks. All groups, except G0, received 4 injections of the carcinogen 1,2-dimethyl-hydrazine (DMH), 40mg/kg, in the first 2 weeks. At the end of protocol, samples were collected from liver and colon for analysis. Statistical analysis was performed by Anova test, followed by Tukey\u27s post hoc (pG4), p0.05) among the experimental groups. This study emphasizes the suppressive effects of melatonin in early markers of colonic carcinogenesis and shows for the first time that the benefits of exercise may be reverted by a reduced activity of the pineal gland

Influence pineal gland on experimental colon carcinogenesis in rats submitted to physical exercise

O exercício físico tem sido proposto como uma terapia não farmacológica eficaz para a prevenção e tratamento de neoplasias, com destaque ao câncer de cólon. O presente estudo visa investigar o papel da glândula pineal sobre carcinogênese colônica experimental de ratos submetidos ao exercício físico Dessa forma, propusemos investigar os biomarcadores colônicos de câncer, foco de cripta aberrante (FCA), antígeno nuclear de proliferação nuclear (PCNA), expressão de ciclooxigenase-2 (COX-2) e Caspase 3. Além de parâmetros oxidativos hepáticos de peroxidaçao lipídica e gluationa reduzida (GSH). O Estudo foi conduzido através dos grupos experimentais controle (C), luz contínua (L), Exercício (E) e luz contínua associada ao Exercício (LE) e os mesmos grupos expostos ao carcinógeno químico 1,2-Dimetilhidrazina (DMH). Exercício físico foi realizado pelo modelo de natação, 5 dias por semana durante 10 semanas. Após o periodo de treinamento, os animais foram sacrificados, sendo coletadas amostras de sangue e fígado e colón para análises. O estudo do fígado revelou uma significativa influência do DMH na modulação dos parâmetros oxidativos. Já as análises colônicas dos FCAs e do PCNA mostraram-se controlados pelo exercício físico realizado em condições de normais do ritmo circadiano ao passo que em condições de desbalanço fisiológico da glândula pineal pela exposição luz constante, esses mesmos efeitos foram revertidos em comparação ao demais grupos (LED>LD>D>ED=p LD> D> ED = p <0.001), increase accompanied by reduced plasma levels of melatonin in this group. In conclusion, our data call attention to the strong influence of the pineal gland on the complex adaptations of physical exercise on colonic mucosa of rats exposed to a chemical carcinogen

Influence pineal gland on experimental colon carcinogenesis in rats submitted to physical exercise

O exercício físico tem sido proposto como uma terapia não farmacológica eficaz para a prevenção e tratamento de neoplasias, com destaque ao câncer de cólon. O presente estudo visa investigar o papel da glândula pineal sobre carcinogênese colônica experimental de ratos submetidos ao exercício físico Dessa forma, propusemos investigar os biomarcadores colônicos de câncer, foco de cripta aberrante (FCA), antígeno nuclear de proliferação nuclear (PCNA), expressão de ciclooxigenase-2 (COX-2) e Caspase 3. Além de parâmetros oxidativos hepáticos de peroxidaçao lipídica e gluationa reduzida (GSH). O Estudo foi conduzido através dos grupos experimentais controle (C), luz contínua (L), Exercício (E) e luz contínua associada ao Exercício (LE) e os mesmos grupos expostos ao carcinógeno químico 1,2-Dimetilhidrazina (DMH). Exercício físico foi realizado pelo modelo de natação, 5 dias por semana durante 10 semanas. Após o periodo de treinamento, os animais foram sacrificados, sendo coletadas amostras de sangue e fígado e colón para análises. O estudo do fígado revelou uma significativa influência do DMH na modulação dos parâmetros oxidativos. Já as análises colônicas dos FCAs e do PCNA mostraram-se controlados pelo exercício físico realizado em condições de normais do ritmo circadiano ao passo que em condições de desbalanço fisiológico da glândula pineal pela exposição luz constante, esses mesmos efeitos foram revertidos em comparação ao demais grupos (LED>LD>D>ED=p<0.001), aumento este acompanhado pela redução dos níveis plasmáticos de melatonina neste grupo. Em conclusão, nossos dados alertam para a forte influência da glândula pineal sobre o complexo de adapatações do exercício físico no tecido colônico de ratos expostos a um carcinógeno químico.Physical activity has been proposed as a nonpharmacologic therapy for the prevention and treatment of cancer patients, with emphasis on colon cancer. The current study aims to investigate the role of the pineal gland on experimental colon carcinogenesis in rats submitted to physical exercise. We proposed to analyze cancer colonics biomarkers, Aberrant Foci Crypt (ACFs), proliferating cell nuclear antigen (PCNA) and Caspase-3, inflammation parameters cyclooxigenase-2 (COX-2) and liver oxidative enzymes reduced glutathione (GSH) and lipid peroxidation (MDA). Experimental design was constructed by control group (C), continuous light (L), exercise (E) and continuous light plus exercise (LE) and the same groups with chemical carcinogen 1,2 dimethyl-hydrazine (DMH). Exercise training groups were performed swimming exercise 5 d-wk1 for 10 wk. After training period rats were sacrificed. Blood samples and liver were collected to analyses and colon was processed for histological and immunohistochemistry examination. The study of the liver revealed a significant effect of DMH in the modulation of oxidative parameters. Since the analysis of colonic FCAs and PCNA were shown to be controlled by exercise carried out with a normal circadian rhythm while in conditions of physiological imbalance of the pineal gland by constant light exposure, these effects were reversed in comparison to other groups (LED> LD> D> ED = p <0.001), increase accompanied by reduced plasma levels of melatonin in this group. In conclusion, our data call attention to the strong influence of the pineal gland on the complex adaptations of physical exercise on colonic mucosa of rats exposed to a chemical carcinogen

The Effects of Acute Exercise and Exercise Training on Plasma Homocysteine: A Meta-Analysis.

BACKGROUND:Although studies have demonstrated that physical exercise alters homocysteine levels in the blood, meta-analyses of the effects of acute exercise and exercise training on homocysteine blood concentration have not been performed, especially regarding the duration and intensity of exercise, which could affect homocysteine levels differently. OBJECTIVE:The aim of this meta-analysis was to ascertain the effects of acute exercise and exercise training on homocysteine levels in the blood. METHOD:A review was conducted according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses using the online databases PubMed, SPORTDiscus, and SciELO to identify relevant studies published through June 2015. Review Manager was used to calculate the effect size of acute exercise and exercise training using the change in Hcy plasmaserum concentration from baseline to post-acute exercise and trained vs. sedentary control groups, respectively. Weighted mean differences were calculated using random effect models. RESULTS:Given the abundance of studies, acute exercise trials were divided into two subgroups according to exercise volume and intensity, whereas the effects of exercise training were analyzed together. Overall, 22 studies with a total of 520 participants indicated increased plasma homocysteine concentration after acute exercise (1.18 μmol/L, 95% CI: 0.71 to 1.65, p < .01). Results of a subgroup analysis indicated that either long-term exercise of low-to-moderate intensity (1.39 μmol/L, 95% CI: 0.9 to 1.89, p < .01) or short-term exercise of high intensity (0.83 μmol/L, 95% CI: 0.19 to 1.40, p < .01) elevated homocysteine levels in the blood. Increased homocysteine induced by exercise was significantly associated with volume of exercise, but not intensity. By contrast, resistance training reduced plasma homocysteine concentration (-1.53 μmol/L, 95% CI: -2.77 to -0.28, p = .02), though aerobic training did not. The cumulative results of the seven studies with a total of 230 participants in exercise training analysis did not demonstrate a significant impact on homocysteine levels in the blood (-0.56 μmol/L, 95% CI: -1.61 to 0.50, p = .23). CONCLUSIONS:Current evidence demonstrates that acute exercise increases homocysteine levels in the blood independent of exercise duration and intensity. Resistance, but not aerobic training decreases plasma homocysteine levels

Characteristics of studies included in the acute exercise analysis (outcome 1).

<p>Characteristics of studies included in the acute exercise analysis (outcome 1).</p

Meta-analysis performed on the effects of exercise training on blood Hcy concentration demonstrated as trained vs sedentary control groups.

<p>Calculation based on random effects model. Results are expressed as weighted mean difference (WMD) of Hcy (μmol/l) and 95% confidence intervals (95% CI).</p

Bubble plot showing the dose–response relationship between the mean volume (A) and Intensity (B) of exercise intervention and effect size changes for Hcy plasma levels (%) for the eighteen included studies.

<p>For one single continuous variable, the fitted regression line together with circles representing the estimates from each study, sized according to precision of each estimate in the fitted random-effects meta-regression. Studies included: Murawaska-Cialowicz [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151653#pone.0151653.ref042" target="_blank">42</a>], Deminice et al. [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151653#pone.0151653.ref053" target="_blank">53</a>], Iglesias-Gutiérrez et al. [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151653#pone.0151653.ref033" target="_blank">33</a>], Hammouda et al. [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151653#pone.0151653.ref034" target="_blank">34</a>], McAnulty et al. [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151653#pone.0151653.ref044" target="_blank">44</a>], Bizheh [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151653#pone.0151653.ref048" target="_blank">48</a>], Benedini et al. [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151653#pone.0151653.ref051" target="_blank">51</a>], Venta et al. [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151653#pone.0151653.ref035" target="_blank">35</a>], Subaşı et al. [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151653#pone.0151653.ref047" target="_blank">47</a>], Gelecek et al. [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151653#pone.0151653.ref045" target="_blank">45</a>], Real et al. [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151653#pone.0151653.ref052" target="_blank">52</a>], O’dochartaigh et al. [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151653#pone.0151653.ref039" target="_blank">39</a>], König et al. [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151653#pone.0151653.ref049" target="_blank">49</a>], Herrmann et al. [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151653#pone.0151653.ref050" target="_blank">50</a>], De Crée et al. [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151653#pone.0151653.ref040" target="_blank">40</a>], De Crée et al. [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151653#pone.0151653.ref041" target="_blank">41</a>], Wright et al. [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151653#pone.0151653.ref046" target="_blank">46</a>].</p

PRISMA flow diagram of the study selection process.

<p>After careful discussion between the 2 reviewers, two outcomes were identified and included in the meta-analysis.</p

Characteristics of studies included in the exercise training analysis (outcome 2).

<p>Characteristics of studies included in the exercise training analysis (outcome 2).</p