Volume 32, Issue 1 (3-2025)
RJMS 2025, 32(1): 1-11 |
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Research code: 1-12
Ethics code: IR.IAU.SARI.REC.1401.107
Clinical trials code: 1-12-ف
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barghahi M, farzanegi P, feli kohi kheili F. The Effect of Six Weeks of Intense Intermittent Exercise with Ginger Extract on the Apoptotic Factors of Heart Tissue in Breast Cancer Rats. RJMS 2025; 32 (1) :1-11
URL: http://rjms.iums.ac.ir/article-1-6540-en.html
URL: http://rjms.iums.ac.ir/article-1-6540-en.html
Associate Professor, Department of Exercise Physiology, Sari Branch, Islamic Azad University, Sari, Iran , parvin.farzanegi@gmail.com
Abstract: (652 Views)
Background & Aims: Breast cancer is one of the most malignant cancers in women, accounting for approximately 28.9% of all cancers and 17.6% of all cancer deaths in women (1). Studies show that genetics (2) and environmental factors such as diet and physical inactivity are risk factors for breast cancer (3). Therefore, a combination of predisposing genes and unhealthy lifestyle can be a potentially modifiable risk factor for cancer. Patients with breast cancer typically suffer from various comorbidities such as diabetes, obstructive pulmonary disease, heart disease, arthritis, or hypertension. The occurrence of these diseases increases the risk of cardiovascular disease in people with breast cancer (4).
One of the factors that may be involved in breast cancer and subsequent mortality is apoptosis. Apoptosis is a physiological cell death that, under normal conditions, eliminates old, damaged, redundant, and harmful cells and is essential for tissue development and homeostasis. Apoptosis plays a role in tissue repair and renewal, as well as the elimination of autoreactive T cells. Therefore, any disruption in the apoptosis process leads to disease, which can be caused by a decrease or increase in cell death, which leads to the development and growth of cancer cells and autoimmune disorders (6).
Previous studies related to the effects of physical activity and cancer on quality of life, muscle strength and endurance, and functional indices of patients with cancer have been investigated, and few studies have focused on molecular cellular mechanisms. Therefore, it is necessary to investigate the mechanisms that affect the physiology of heart tissue in breast cancer patients through physical activity and herbal medicine. Therefore, considering the relationship between breast cancer and apoptosis on the one hand (21), as well as the positive effects of exercise in establishing homeostasis and supportive effects in reducing tumor volume in cancer patients on the other hand, and research conducted on the anti-inflammatory and anti-cancer properties of ginger, this study aimed to investigate the effects of six weeks of intense intermittent exercise with ginger extract on apoptotic factors in heart tissue of breast cancer model rats.
Methods: In this experimental study, 35 female Balbsi mice aged 6 to 8 weeks were randomly assigned to 5 groups: healthy control, cancer control, ginger, HIT training, and HIT training-ginger. The rats were implanted with tumors and were cancerous. The training groups performed 5 sessions per week for 6 weeks, each session lasting 30 minutes, including a 5-minute warm-up at an intensity of 30 to 40% of VO2max, 6 intervals (3 minutes and 20 seconds at an intensity of 85 to 90% and a 1-minute recovery at an intensity of 30 to 35% of VO2max between each interval), and a 5-minute cool-down at an intensity of 30 to 40% of VO2max. Ginger extract was also injected subcutaneously at a dose of 20 mg/kg of body weight to the mice in the supplement and exercise-supplement groups every day.
At the end of the training period, 48 hours after the last training session, with 10 to 12 hours of night fasting, the rats were anesthetized by intraperitoneal injection of a combination of ketamine and xylazine and tissue sampling was performed. Laboratory analysis of BAX and BCL-2 gene levels of cardiac tissue was determined using special commercial kits by real-time PCR.
Descriptive statistics were used to classify the data obtained from this study. Shapirovilk test was used to determine the normality of data distribution. One-way analysis of variance was used to determine the significance of the difference between the variables and the interaction between them, and if the data were significant, the Tukey post hoc test was used to determine the location of the difference. Findings were evaluated at 95% confidence level (P≤0.05).
Results: The results showed that six weeks of HIT training combined with ginger extract consumption had a significant effect on Bcl-2 and Bax genes in the heart tissue of experimental breast cancer mouse models.
Conclusion: Exercise training has been shown to induce apoptosis, a natural process for the elimination of damaged cells in which significant inflammatory responses do not occur. This process ensures normal body function (33). The mechanisms of protection against apoptosis due to prevention may be affected by NF-kB, which prevents susceptibility to apoptosis and can promote the upregulation of the anti-apoptotic gene Bcl-2 and the downregulation of the pro-apoptotic gene BAX (34). High expression of the Bcl-2 gene and low expression of the BAX gene reduce cardiac tissue damage and improve cardiac function.
Regarding the effect of ginger on apoptotic factors, it can be stated that the consumption of antioxidants leads to a decrease in cellular apoptosis and also improves the disease by reducing the level of oxidative stress (36). Because tumor progression is closely related to inflammation and oxidative stress, a compound that has anti-inflammatory or antioxidant properties can be an anti-malignant agent for cells (37).
The combination of exercise and ginger represents a promising advanced approach with great therapeutic potential for breast cancer. Recent studies provide new targets for future breast cancer treatments. The lack of measurement of genes downstream and upstream of apoptosis factors is a limitation of this study, which could have helped to determine the more precise mechanism of the intervention effect, and therefore should be considered in future studies. Also, in this study, the results showed synergy between exercise and ginger extract in improving apoptotic factors in rats with breast cancer, which should be considered by physicians and exercise physiologists.
One of the factors that may be involved in breast cancer and subsequent mortality is apoptosis. Apoptosis is a physiological cell death that, under normal conditions, eliminates old, damaged, redundant, and harmful cells and is essential for tissue development and homeostasis. Apoptosis plays a role in tissue repair and renewal, as well as the elimination of autoreactive T cells. Therefore, any disruption in the apoptosis process leads to disease, which can be caused by a decrease or increase in cell death, which leads to the development and growth of cancer cells and autoimmune disorders (6).
Previous studies related to the effects of physical activity and cancer on quality of life, muscle strength and endurance, and functional indices of patients with cancer have been investigated, and few studies have focused on molecular cellular mechanisms. Therefore, it is necessary to investigate the mechanisms that affect the physiology of heart tissue in breast cancer patients through physical activity and herbal medicine. Therefore, considering the relationship between breast cancer and apoptosis on the one hand (21), as well as the positive effects of exercise in establishing homeostasis and supportive effects in reducing tumor volume in cancer patients on the other hand, and research conducted on the anti-inflammatory and anti-cancer properties of ginger, this study aimed to investigate the effects of six weeks of intense intermittent exercise with ginger extract on apoptotic factors in heart tissue of breast cancer model rats.
Methods: In this experimental study, 35 female Balbsi mice aged 6 to 8 weeks were randomly assigned to 5 groups: healthy control, cancer control, ginger, HIT training, and HIT training-ginger. The rats were implanted with tumors and were cancerous. The training groups performed 5 sessions per week for 6 weeks, each session lasting 30 minutes, including a 5-minute warm-up at an intensity of 30 to 40% of VO2max, 6 intervals (3 minutes and 20 seconds at an intensity of 85 to 90% and a 1-minute recovery at an intensity of 30 to 35% of VO2max between each interval), and a 5-minute cool-down at an intensity of 30 to 40% of VO2max. Ginger extract was also injected subcutaneously at a dose of 20 mg/kg of body weight to the mice in the supplement and exercise-supplement groups every day.
At the end of the training period, 48 hours after the last training session, with 10 to 12 hours of night fasting, the rats were anesthetized by intraperitoneal injection of a combination of ketamine and xylazine and tissue sampling was performed. Laboratory analysis of BAX and BCL-2 gene levels of cardiac tissue was determined using special commercial kits by real-time PCR.
Descriptive statistics were used to classify the data obtained from this study. Shapirovilk test was used to determine the normality of data distribution. One-way analysis of variance was used to determine the significance of the difference between the variables and the interaction between them, and if the data were significant, the Tukey post hoc test was used to determine the location of the difference. Findings were evaluated at 95% confidence level (P≤0.05).
Results: The results showed that six weeks of HIT training combined with ginger extract consumption had a significant effect on Bcl-2 and Bax genes in the heart tissue of experimental breast cancer mouse models.
Conclusion: Exercise training has been shown to induce apoptosis, a natural process for the elimination of damaged cells in which significant inflammatory responses do not occur. This process ensures normal body function (33). The mechanisms of protection against apoptosis due to prevention may be affected by NF-kB, which prevents susceptibility to apoptosis and can promote the upregulation of the anti-apoptotic gene Bcl-2 and the downregulation of the pro-apoptotic gene BAX (34). High expression of the Bcl-2 gene and low expression of the BAX gene reduce cardiac tissue damage and improve cardiac function.
Regarding the effect of ginger on apoptotic factors, it can be stated that the consumption of antioxidants leads to a decrease in cellular apoptosis and also improves the disease by reducing the level of oxidative stress (36). Because tumor progression is closely related to inflammation and oxidative stress, a compound that has anti-inflammatory or antioxidant properties can be an anti-malignant agent for cells (37).
The combination of exercise and ginger represents a promising advanced approach with great therapeutic potential for breast cancer. Recent studies provide new targets for future breast cancer treatments. The lack of measurement of genes downstream and upstream of apoptosis factors is a limitation of this study, which could have helped to determine the more precise mechanism of the intervention effect, and therefore should be considered in future studies. Also, in this study, the results showed synergy between exercise and ginger extract in improving apoptotic factors in rats with breast cancer, which should be considered by physicians and exercise physiologists.
Type of Study: Research |
Subject:
Exercise Physiology
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