scholarly journals Synergistic Effects of Exercise Training and Vitamin D Supplementation on Mitochondrial Function of Cardiac Tissue, Antioxidant Capacity, and Tumor Growth in Breast Cancer in Bearing-4T1 Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Ali Jafari ◽  
Dariush Sheikholeslami-Vatani ◽  
Farnoosh Khosrobakhsh ◽  
Neda Khaledi

Both regular exercise training and vitamin D consumption are beneficial for patients with cancer. The study investigated the effects of interval exercise training (IET) or/and vitamin D supplementation on the gene expression involved in mitochondrial function of heart tissue, tumor size, and total antioxidant capacity (TAC) in breast cancer (BC) model mice. We assigned random 40 female NMRI mice to five equal groups (n = 8); the healthy control group (H.C), cancer control group (Ca.C), cancer with the vitamin D group (Ca.VD), cancer exercise group (Ca.Ex), and cancer exercise along with the vitamin D group (Ca.Ex.VD). Forty-eight hours after treatment, we anesthetized the animals and performed the isolation of heart tissue and blood serum for further studies. The results showed that the lowest mean body weight at the end of the treatments was related to Ca.C (p = 0.001). Vitamin D treatment alone has increased tumor volume growth by approximately 23%; in contrast, co-treatment with exercise and vitamin D inhibited tumor growth in mice (P = 0.001), compared with the cancer control (12%). TAC levels were higher in the group that received both vitamin D and exercise training (Ca.Ex.VD) than in the other treatment groups (Ca.VD and Ca.Ex) (p = 0.001). In cardiac tissue, vitamin D treatment induces an elevation significantly of the mRNA expression of Pgc1−α, Mfn-1, and Drp-1 genes (p = 0.001). The study has shown the overexpression of vitamin D in female mice, and synergistic effects of IET with vitamin D on weight loss controlling, antitumorigenesis, improvement of antioxidant defense, and the modulation of gene expression. The synergistic responses were likely by increasing mitochondrial fusion and TAC to control oxidative stress. We recommended being conducted further studies on mitochondrial dynamics and biogenesis focusing on risk factors of cardiovascular disease (CVD) in patients with BC.

QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
F M A Diab ◽  
N A Nassef ◽  
M S Abdelhamid ◽  
Y M K Amin

Abstract Background Doxorubicin-induced cardiotoxicity is a worldwide problem. Vitamin D is a well-known beneficial vitamin for bone growth and calcium homeostasis but recently it is also known for its cardioprotective effects. The aim of this study is to investigate the potential protective role of vitamin D on the cardiac dysfunction induced by chronic doxorubicin exposure, and to throw more light on the possible underlying mechanism (s) for such effect. Materials and Methods: 70 female Albino-rats were divided into 4 groups; control group (C), Doxorubicin-treated group (Dox): given i.p. injection of Dox in a dose of 2.5 mg/kg body weight (cumulative dose: 15 mg/kg) over 3 weeks, vitamin Dsupplemented group (Vit D): given vitamin D by oral gavage in a dose of 500 IU/kg daily, 5 days a week, also for 3 weeks and the combined Doxorubicintreated+vitamin D-supplemented group (Dox+Vit D). At the end of the experiment, ECG was recorded and in vitro isolated heart study was performed on Langendoroff preparation to measure peak tension (PT), time to peak tension (TPT), half relaxation time (HRT) and myocardial flow rate (MFR). Body and cardiac weights, plasma levels of brain naturetic peptide (BNP), cardiac troponin I (cTnI), vitamin D and total calcium and cardiac tissue heat shock protein 20, total antioxidant capacity (TAC) and malondialdehyde (MDA) were measured. Also, cardiac tissues were histopathologically assessed. Results: Dox-treated rats showed significant decrease in the final body weight (fBW), significant prolongation of the P-R interval, QRS duration, observed Q-T (Q-TO) and corrected Q-T (Q-Tc) with significant depression of the R voltage. In addition, there was a significant decrease in the in vitro heart rate, significant depression in PT, PT/LV and MFR together with significant prolongation in TPT& 3 HRT. These changes were accompanied by significant elevation of plasma BNP, cTnI and in cardiac tissue MDA and a significant decrease in plasma vit D, total calcium and cardiac tissue TAC and HSP20. Histopathological examination revealed markedly distorted muscle fibers with indistinct cell borders, bright eosinophilic cytoplasm, intra-cytoplasmic vacuoles and small pyknotic nuclei or absent nuclei, together with interstitial edema & aggregates of inflammatory cells and thick irregular collagen fibers in between the muscle fibers. Concomitant supplementation of vitamin D to the doxorubicin treated rats resulted in significant decrease in PR interval, QRS duration, MDA and significant increase PT, PT/LV, MFR, MFR/LV, plasma vitamin D, total calcium and TAC compared to the Dox treated rats to be insignificantly different from the control group. Plasma BNP and cTnI were significantly decreased while cardiac HSP20 was significantly increased compared to the Dox-treated rats, yet these parameters were still significant from the control group. Meanwhile, fBW, Q-TO and Q-Tc intervals, and TPT remained insignificantly changed from the DOX group. These findings were associated by regaining the normal collagen fiber distribution between cardiac muscle fibers with resolution of interstitial edema. Conclusion: Vitamin D supplementation can partially mitigate cardiac dysfunction induced by chronic doxorubicin by improving the cardiac antioxidant state and heat shock protein 20 level. Key words: Doxorubicin, cardiac dysfunction, vitamin D, isolated heart studies, BNP, HSP20.


Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 564
Author(s):  
Agnieszka Radom ◽  
Andrzej Wędrychowicz ◽  
Stanisław Pieczarkowski ◽  
Szymon Skoczeń ◽  
Przemysław Tomasik

Maintaining an optimal vitamin D concentration reduces the risk of recurrence and extends survival time in patients after breast cancer treatment. Data on vitamin D deficiency among Polish women after breast cancer therapy are limited. Thus, the aim of the study was the analysis of vitamin D status in post-mastectomy patients, considering such factors as seasons, social habits, vitamin D supplementation and its measurements. The study involved 94 women after breast cancer treatment. Serum vitamin D concentration was measured, and a questionnaire, gathering demographic and clinical data regarding cancer, diet, exposure to sun radiation, and knowledge of recommendations on vitamin D supplementation, was delivered twice, in both winter and in summer. The control group consisted of 94 age-matched women with no oncological history. In women after breast cancer treatment, 25-hydroxyvitamin D (25(OH)D) deficiency was much more frequent than in the general population. Only about half of the patients supplemented vitamin D at the beginning of the study. After the first test and the issuing of recommendations on vitamin D supplementation, the percentage of vitamin D supplemented patients increased by about 30% in study groups. The average dose of supplement also increased. None of the women that were not supplementing vitamin D and were tested again in winter had optimal 25(OH)D concentration. It was concluded that vitamin deficiency is common in women treated for breast cancer. Medical advising about vitamin D supplementation and monitoring of 25(OH)D concentration should be improved.


2020 ◽  
Vol 24 (4) ◽  
pp. 308-319
Author(s):  
Kobra Soleymani ◽  
◽  
Asieh Abbassi Daloii ◽  
Ali Reza Barari ◽  
Ayoub Saeidi ◽  
...  

Background: The effects of exercise and stevia extract on diabetes-related indicators have been already reported, but their cardiac benefits on Type 1 Diabetes (T1D) are unclear. Objective: This study aims to evaluate the effect of eight weeks of endurance training and stevia supplementation on gene expression levels of Atrial Natriuretic Peptide (ANP) and β-Myosin Heavy Chain (β-MHC) in the heart tissue of T1D rats. Methods: In this experimental study, 25 rats with the average weight of 250-300 g were divided into five groups; healthy control, diabetic control, diabetic+supplementation, diabetic+training, and diabetic+training+supplementation. T1D was induced by intraperitoneal injection of streptozotocin (55 mg/kg/ body weight). Endurance training was performed 5 days a week at a speed of 20-30 meters per minute on a surface with a zero slope for 8 weeks. Stevia was gavaged in a dose of 250 mg/kg/body weight. Rats were slaughtered 48 hours after the last training session. Cardiac tissue was used to measure the parameters. The gene expression of ANP and b-MHC in cardiac tissue was measured by real-time Polymerase Chain Reaction (PCR) method. Data were analyzed by using one-way ANOVA and Bonferroni post hoc test. Findings: The gene expression levels of ANP and β-MHC were significantly higher in the diabetic control group compared to the healthy control group (P=0.001), and significantly lower in the diabetic+training and diabetic+training+supplementation groups compared to the diabetic control group (P=0.001). Conclusion: Endurance training and stevia supplementation can have beneficial effects on the heart of T1D rats.


2021 ◽  
Author(s):  
Mi Xiang ◽  
Xiaomin Sun ◽  
Junxiang Wei ◽  
Zhen-Bo Cao

Abstract BackgroundAlthough approximately 50% of Chinese T2DM patients have vitamin D deficiency, studies regarding vitamin D supplementation on IR have mainly focused on non-Asians. Endurance exercise training (ET) enhances insulin-mediated glucose metabolism, which plays a critical role in T2DM prevention and control. However, the combined effects of vitamin D supplementation and ET on IR in T2DM patients are unclear.Methods and analysisWe propose a randomized controlled trial among 60 T2DM patients with vitamin D deficiency to evaluate the combined effects of vitamin D supplementation and endurance training on IR. The participants will be randomly allocated to the vitamin D group, vitamin D combined with exercise training group, exercise training group, and control group (CG) using a computer-generated random number sequence. At baseline, participants will undergo a medical review, anthropometric measurements, dual X-ray absorptiometry, a 75-g oral glucose tolerance test, ankle-brachial index measurements, and physical fitness measurements and will complete related lifestyle questionnaires. In a 3-month intervention period, vitamin D intervention group will receive a dose of 1000IU daily; exercise group will perform a 1-hour endurance exercise 3 times per week (maximal heart rate, 60%–80%), and the control group will receive apparently identical tablets. Additionally, all participants will be advised to maintain their normal diet and physical activities during the intervention. All measurements will be repeated at 3-month follow-up after the intervention with the primary outcome measure expressed as a change from baseline in insulin sensitivity and secretion. Secondary outcome measures will compare the changes in anthropometry, ankle-brachial index, and physical fitness factors. Data will be managed and analyzed using the Statistical Package for the Social Sciences.DiscussionThis is the first study to conduct a randomized trial to clearly determine the independent and combined effects of vitamin D supplementation and endurance exercise trial on IR in Chinese T2DM patients as measured by OGTT. The findings from the proposed study will not only provide new evidences that vitamin D supplementation plays an important role in reducing IR but also develop a simple and efficient method to improve IR and associated metabolic diseases for T2DM patients.Trial registrationChinese Clinical Trial Registry, ChiCTR1800015383, Registered 28 March 2018, http://www.chictr.org.cn


2019 ◽  
Vol 19 (8) ◽  
pp. 570-578 ◽  
Author(s):  
Elahe S. Hosseini ◽  
Hamed H. Kashani ◽  
Hossein Nikzad ◽  
Alireza Soleimani ◽  
Hamed Mirzaei ◽  
...  

Background: This study was conducted to determine the effects of vitamin D supplementation on some of the gene expressions related to insulin and lipid metabolism in diabetic hemodialysis (HD) patients. Methods: A double-blind, randomized, placebo-controlled clinical trial was carried out in 55 patients with diabetic HD. The current project used two groups in which each subject received vitamin D supplements (50,000 IU, n=28) or placebo (50,000 IU, n=27) every 2 weeks for 12 weeks. Gene expression analyses (RT-PCR) were included to obtain the rate of gene expression of the related insulin and lipid metabolism genes in peripheral blood mononuclear cells (PBMCs) of patients with diabetic HD. Results: Our data revealed that consumption of vitamin D supplementation enables to overexpress the peroxisome proliferation-activated receptor gamma (PPAR-γ) (P=0.001), AKT (P=0.04), PI3K (P=0.02), insulin receptor substrate-1 (IRS1) (P0.008) and glucose transporter type 4 (GLUT-4) (P=0.01) and downregulate the expression of protein kinase C (PKC) (P=0.001) in patients with diabetic HD than control group following the 12-week intervention. In addition, vitamin D supplementation downregulated low-density lipoprotein receptor (LDLR) (P=0.03) expression in the subjects with diabetic HD than the control group. Vitamin D supplementation did not show any effects on the expression of pyruvate dehydrogenase kinase 1 (PDK1) (P=0.37), IRS2 (P=0.90) and lipoprotein (a) [Lp(a)] (P=0.05). Conclusions: Our findings confirmed that diabetic HD subjects who received the vitamin D supplementation (for 12 weeks), showed a significant overexpression in the PPAR-γ, AKT, PI3K, IRS1 and GLUT4 genes, and also showed a significant downregulation in the PKC and LDLR genes. Moreover, no effects on PDK1, IRS2 and Lp(a) expression were observed.


Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Mi Xiang ◽  
Xiaomin Sun ◽  
Junxiang Wei ◽  
Zhen-Bo Cao

Abstract Background Although approximately 50% of Chinese with type 2 diabetes mellitus (T2DM) patients have vitamin D deficiency, studies regarding vitamin D supplementation on insulin resistance (IR) have mainly focused on non-Asians. Endurance exercise training (ET) enhances insulin-mediated glucose metabolism, which plays a critical role in T2DM prevention and control. However, the combined effects of vitamin D supplementation and ET on IR in T2DM patients are unclear. The objectives of this study is to investigate the synergistic effect of vitamin D supplementation combined with exercise training intervention on IR in T2DM patients. Methods and analysis We propose a 3-month randomized controlled trial among 60 T2DM patients aged 40–65, newly diagnosed with T2DM ≤ 1 year, and with stable HbA1c level (≤ 8.0%) in the past 3 months. The participants will be randomly allocated to the vitamin D group, vitamin D combined with exercise training group, exercise training group, and control group (CG) using a computer-generated random number sequence. At baseline, participants will undergo a medical review, anthropometric measurements, dual X-ray absorptiometry, a 75-g oral glucose tolerance test (OGTT), ankle-brachial index measurements, and physical fitness measurements and will complete related lifestyle questionnaires. Fasting blood lipid and glucose levels were also measured. In a 3-month intervention period, vitamin D intervention group will receive a dose of 1000 IU daily; exercise group will perform a 1-h endurance exercise 3 times per week (maximal heart rate, 60–80%), and the control group will receive apparently identical tablets. Additionally, all participants will be advised to maintain their normal diet and physical activities during the intervention. All measurements will be repeated at 3-month follow-up after the intervention with the primary outcome measure expressed as a change from baseline in insulin sensitivity and secretion. Secondary outcome measures will compare the changes in anthropometry, ankle-brachial index, and physical fitness factors (e.g., peak oxygen uptake, hand grip strength). Data will be managed and analyzed using the Statistical Package for the Social Sciences. Discussion This is the first study to conduct a randomized trial to clearly determine the independent and combined effects of vitamin D supplementation and endurance exercise trial on IR in Chinese T2DM patients as measured by OGTT. The findings from the proposed study will not only provide new evidences that vitamin D supplementation plays an important role in IR management but also develop a simple and efficient method to improve IR-associated metabolic diseases for T2DM patients. Trial registration Chinese Clinical Trial Registry ChiCTR1800015383, Registered on 28 March 2018


2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Vahid Khedmati Zare ◽  
Maedeh Javadi ◽  
Sadegh Amani-shalamzari ◽  
Mojtaba Kaviani

Abstract Background This study aimed to examine the effect of yoga training combined with vitamin D supplementation on the expression of survival-related genes in leukocytes and psycho-physical status in breast cancer survivors. Methods Thirty breast cancer survivor women (age, 48 ± 8 yrs) were randomly assigned into three groups: high dose (4000 IU) of vitamin D supplementation (HD) (n = 10); yoga training with a high dose of vitamin D (Y + HD); (n  = 10); yoga training with a low dose (2000 IU) of vitamin D (Y + LD) (n = 10). Participants performed the Hatha yoga style twice a week. Blood samples and a battery of psychological and physical tests were taken before and after the completion of interventions. Expression of p53, NF-κB, Bcl2, and Bax genes was measured in leukocytes. Results Body fat percentage (ηp2 = 0.36), shoulder flexibility (ηp2 = 0.38), Rockport walk tests (ηp2 = 0.49), and anxiety (ηp2 = 0.52) were significantly improved in both the Y + HD and Y + LD groups compared to the HD group (p < 0.05). P53 was significantly over-expressed in the Y + HD group while Bcl2 upregulated in both the Y + HD and Y + LD groups. NF-κB and Bax expression downregulated in all groups but were not statistically significant. Conclusion yoga training combined with low and high doses of VD improved physical fitness and psychological measures while only in combination with a high dose of VD positively modified the leukocytes cell survival-related gene expression.


2021 ◽  
pp. 1-10
Author(s):  
Sanaa A. El-Benhawy ◽  
Samia A. Ebeid ◽  
Nadia A. Abd El Moneim ◽  
Rabie R. Abdel Wahed ◽  
Amal R.R. Arab

BACKGROUND: Altered cadherin expression plays a vital role in tumorigenesis, angiogenesis and tumor progression. However, the function of protocadherin 17 (PCDH17) in breast cancer remains unclear. OBJECTIVE: Our target is to explore PCDH17 gene expression in breast carcinoma tissues and its relation to serum angiopoietin-2 (Ang-2), carbonic anhydrase IX (CAIX) and % of circulating CD34+ cells in breast cancer patients (BCPs). METHODS: This study included Fifty female BCPs and 50 healthy females as control group. Cancerous and neighboring normal breast tissues were collected from BCPs as well as blood samples at diagnosis PCDH17 gene expression was evaluated by RT-PCR. Serum Ang-2, CAIX levels were measured by ELISA and % CD34+ cells were assessed by flow cytometry. RESULTS: PCDH17 was downregulated in cancerous breast tissues and its repression was significantly correlated with advanced stage and larger tumor size. Low PCDH17 was significantly correlated with serum Ang-2, % CD34+ cells and serum CAIX levels. Serum CAIX, Ang-2 and % CD34+ cells levels were highly elevated in BCPs and significantly correlated with clinical stage. CONCLUSIONS: PCDH17 downregulation correlated significantly with increased angiogenic and hypoxia biomarkers. These results explore the role of PCDH17 as a tumor suppressor gene inhibiting tumor growth and proliferation.


Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1280
Author(s):  
Jan Mieszkowski ◽  
Andżelika Borkowska ◽  
Błażej Stankiewicz ◽  
Andrzej Kochanowicz ◽  
Bartłomiej Niespodziński ◽  
...  

Purpose: A growing number of studies indicate the importance of vitamin D supplementation for sports performance. However, the effects of a single high-dose vitamin D supplementation on ultramarathon-induced inflammation have not been investigated. We here analyzed the effect of a single high-dose vitamin D supplementation on the inflammatory marker levels in ultramarathon runners after an ultramarathon run (maximal run 240 km). Methods: In the study, 35 runners (amateurs) were assigned into two groups: single high-dose vitamin D supplementation group, administered vitamin D (150,000 IU) in vegetable oil 24 h before the start of the run (n = 16); and placebo group (n = 19). Blood was collected for analysis 24 h before, immediately after, and 24 h after the run. Results: Serum 25(OH)D levels were significantly increased after the ultramarathon in both groups. The increase was greater in the vitamin D group than in the control group. Based on post-hoc and other analyses, the increase in interleukin 6 and 10, and resistin levels immediately after the run was significantly higher in runners in the control group than that in those in the supplementation group. Leptin, oncostatin M, and metalloproteinase tissue inhibitor levels were significantly decreased in both groups after the run, regardless of the supplementation. Conclusions: Ultramarathon significantly increases the serum 25(OH)D levels. Attenuation of changes in interleukin levels upon vitamin D supplementation confirmed that vitamin D has anti-inflammatory effect on exercise-induced inflammation.


2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Márcia Fernanda Correia Jardim Paz ◽  
André Luiz Pinho Sobral ◽  
Jaqueline Nascimento Picada ◽  
Ivana Grivicich ◽  
Antonio Luiz Gomes Júnior ◽  
...  

This study aimed to evaluate DNA damage in patients with breast cancer before treatment (background) and after chemotherapy (QT) and radiotherapy (RT) treatment using the Comet assay in peripheral blood and the micronucleus test in buccal cells. We also evaluated repair of DNA damage after the end of RT, as well as the response of patient’s cells before treatment with an oxidizing agent (H2O2; challenge assay). Fifty women with a mammographic diagnosis negative for cancer (control group) and 100 women with a diagnosis of breast cancer (followed up during the treatment) were involved in this study. The significant DNA damage was observed by increasing in the index and frequency of damage along with the increasing of the frequency of micronuclei in peripheral blood and cells of the buccal mucosa, respectively. Despite the variability of the responses of breast cancer patients, the individuals presented lesions on the DNA, detected by the Comet assay and micronucleus Test, from the diagnosis until the end of the oncological treatment and were more susceptible to oxidative stress. We can conclude that the damages were due to clastogenic and/or aneugenic effects related to the neoplasia itself and that they increased, especially after RT.


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