Effects of Eight-Week High-Intensity Interval Training Combined with Pomegranate Juice Supplementation on Intestinal Lipid Peroxidation and Visceral Fat Mass in Colorectal Cancer-Induced Laboratory Mice
الموضوعات : Sport PhysiologyRazieh Norizadeh Ahari 1 , Seyed Ali Hosseini 2 , Farzaneh Taghian 3 , Khosrow Jalali Dehkordi 4
1 - Department of Sport Physiology, Isf.C., Islamic Azad University, Isfahan, Iran
2 - Department of Sport Physiology, Marv.C., Islamic Azad University, Marvdasht, Iran
3 - Department of Sport Physiology, Isf.C., Islamic Azad University, Isfahan, Iran
4 - Department of Sport Physiology, Isf.C., Islamic Azad University, Isfahan, Iran
الکلمات المفتاحية: High-intensity interval training, Pomegranate juice supplementation, Body composition, Lipid peroxidation, Colorectal cancerr,
ملخص المقالة :
Background: Dysregulation of lipid metabolism and increased lipid peroxidation are key contributors to colorectal cancer (CRC) progression. Considering the limited evidence on the combined effects of high-intensity interval training (HIIT) and pomegranate juice (PJ) supplementation in CRC, the present study aimed to evaluate the impact of an eight-week HIIT program combined with PJ supplementation on intestinal lipid peroxidation and visceral fat mass in CRC-induced laboratory mice.
Methods: In this experimental study, thirty-two male BALB/c mice (18–22 g, 8–10 weeks old) were induced with CRC via subcutaneous injection of 5×10^5 viable CT26 cells and randomly assigned to four groups: (1) CRC, (2) PJ, (3) HIIT, and (4) HIIT+PJ. To assess the effects of CRC itself, eight mice were allocated to a healthy control group (HC), and eight additional mice were included in a Sham group to evaluate culture medium effects. HIIT was performed five sessions per week for eight weeks, progressing from five high-intensity sets in week one to sixteen sets in week eight, at 75–90% of maximal running speed on a 15° incline. PJ supplementation consisted of 5% of the daily drinking water intake. Data were analyzed using one-way ANOVA followed by Tukey’s post hoc test (P ≤ 0.05).
Results: Post-intervention body weight, visceral fat mass, and malondialdehyde (MDA) levels were significantly higher in the CRC group compared to HC (P < 0.001). In contrast, PJ, HIIT, and HIIT+PJ groups exhibited significantly lower body weight and visceral fat compared to CRC (P < 0.001). MDA levels were significantly reduced in HIIT and HIIT+PJ groups relative to CRC (P < 0.05). Moreover, post-intervention body weight, visceral fat mass, and MDA in HIIT and HIIT+PJ groups were significantly lower than in the PJ group (P < 0.05).
Conclusion: Both HIIT and PJ, individually and in combination, effectively improved body composition. However, HIIT alone or combined with PJ exerted more pronounced effects on reducing lipid peroxidation and enhancing body composition compared to PJ supplementation alone.
Al-Muammar, M. N., & Khan, F. (2012). Obesity: the preventive role of the pomegranate (Punica granatum). Nutrition, 28(6), 595-604.
Amirsasan, R., Akbarzadeh, M., & Akbarzadeh, S. (2022). Exercise and colorectal cancer: prevention and molecular mechanisms. Cancer Cell International, 22(1), 247.
Aviram, M., Dornfeld, L., Rosenblat, M., Volkova, N., Kaplan, M., Coleman, R., ... & Fuhrman, B. (2000). Pomegranate juice consumption reduces oxidative stress, atherogenic modifications to LDL, and platelet aggregation: studies in humans and in atherosclerotic apolipoprotein E–deficient mice. The American journal of clinical nutrition, 71(5), 1062-1076.
Aviram, M., Rosenblat, M., Gaitini, D., Nitecki, S., Hoffman, A., Dornfeld, L., ... & Volkova, N. (2013). Pomegranate juice consumption for 3 years by patients with carotid artery stenosis reduces common carotid intima–media thickness, blood pressure and LDL oxidation. Clinical Nutrition, 32(2), 250–257. https://doi.org/10.1016/j.clnu.2012.08.007
Aytac, K. Y., & Yildirim, E. K. (2023). The effect of pomegranate-black carrot juice on serum oxidative stress parameters in rats after exhaustive exercise. Journal of Food Science and Technology, 60(5), 1523–1531. https://doi.org/10.1155/2023/9489018
Banerjee, N., Kim, H., Talcott, S., & Mertens-Talcott, S. (2013). Pomegranate polyphenolics suppressed azoxymethane-induced colorectal aberrant crypt foci and inflammation: possible role of miR-126/VCAM-1 and miR-126/PI3K/AKT/mTOR. Carcinogenesis, 34(12), 2814-2822.
Basu, A., Newman, E. D., Bryant, A. L., Lyons, T. J., & Betts, N. M. (2013). Pomegranate polyphenols lower lipid peroxidation in adults with type 2 diabetes but have no effects in healthy volunteers: a pilot study. Journal of nutrition and metabolism, 2013(1), 708381.
Benedetti, G., Zabini, F., Tagliavento, L., Meneguzzo, F., Calderone, V., & Testai, L. (2023). An overview of the health benefits, extraction methods and improving the properties of pomegranate. Antioxidants, 12(7), 1351.
Catalano, T., Selvaggi, F., Cotellese, R., & Aceto, G. M. (2025). The role of reactive oxygen species in colorectal cancer initiation and progression: Perspectives on theranostic approaches. Cancers, 17(5), 752.
Cho, S. Y., Chung, Y. S., Yoon, H. K., & Roh, H. T. (2022). Impact of exercise intensity on systemic oxidative stress, inflammatory responses, and sirtuin levels in healthy male volunteers. International journal of environmental research and public health, 19(18), 11292.
Cho, S. Y., Chung, Y. S., Yoon, H. K., & Roh, H. T. (2022). Impact of exercise intensity on systemic oxidative stress, inflammatory responses, and sirtuin levels in healthy male volunteers. International journal of environmental research and public health, 19(18), 11292.
Davoodi, S., Ghanbari, F., & Samadi, M. (2020). The effect of endurance exercise training and pomegranate juice consumption on lipid peroxidation and antioxidant status in colon cancer-induced rats. Iranian Journal of Physiology and Sports Research, 12(4), 45–56.
Firouzyar, F., Shamlou Kazemi, S., & Hemmati Afif, A. (2022). The Effect of High-Intensity Interval Training on Antioxidant Factors in Women with Type 2 Diabetes. Journal of Exercise and Health Science, 2(3), 1-14.
Gonzalez-Gutierrez, L., Motiño, O., Barriuso, D., de la Puente-Aldea, J., Alvarez-Frutos, L., Kroemer, G., ... & Senovilla, L. (2024). Obesity-associated colorectal cancer. International Journal of Molecular Sciences, 25(16), 8836.
Janion, K., Szczepańska, E., Nowakowska-Zajdel, E., Strzelczyk, J., & Copija, A. (2020). Selected oxidative stress markers in colorectal cancer patients in relation to primary tumor location—a preliminary research. Medicina, 56(2), 47.
Jee, H., Park, E., Hur, K., Kang, M., & Kim, Y. (2022). High-intensity aerobic exercise suppresses cancer growth by regulating skeletal muscle-derived oncogenes and tumor suppressors. Frontiers in molecular biosciences, 9, 818470.
Jovanović, M., Kovačević, S., Brkljačić, J., & Djordjevic, A. (2023). Oxidative stress linking obesity and cancer: is obesity a ‘radical trigger’to cancer?. International journal of molecular sciences, 24(9), 8452.
Kiyici, F., & Kishali, N. F. (2012). Acute effect of intense exercises on serum superoxide dismutase, catalase and malondialdehyde levels in soccer players. The Journal of sports medicine and physical fitness, 52(1), 107-111.
Koren, A., Rijavec, M., Krumpestar, T., Kern, I., Sadikov, A., Čufer, T., & Korošec, P. (2021). Gene expression levels of the prolyl hydroxylase domain proteins PHD1 and PHD2 but not PHD3 are decreased in primary tumours and correlate with poor prognosis of patients with surgically resected non-small-cell lung cancer. Cancers, 13(10), 2309.
Lu, Y., Wiltshire, H. D., Baker, J. S., & Wang, Q. (2021). Effects of High Intensity Exercise on Oxidative Stress and Antioxidant Status in Untrained Humans: A Systematic Review. Biology 2021, 10, 1272.
Martinez-Useros, J., & Garcia-Foncillas, J. (2016). Obesity and colorectal cancer: molecular features of adipose tissue. Journal of translational medicine, 14(1), 21.
Naghizadeh, N., Riyahi Malayeri, S., Roozbahani, M., Khademi, A., Shirvani, H. The Effectiveness of Endurance Training and Nano Curcumin Supplementation on the Expression of Mir-21and P53 Genes in Brain Tumor Tissue in an Animal Model of Glioblastoma Multiform. Journal of Nutrition,Fasting and Health, 2024; 12(1): 26-35. doi: 10.22038/jnfh.2023.73964.1455
Omidiparsa, M., Nazarali, P., Alizadeh, R., & Rezaeinezhad, N. (2025). Effect of High-intensity Interval Training Combined with Pomegranate Juice Supplementation on the Granulocyte Colony-Stimulating Factor Signaling Pathway in an Animal Model of Colorectal Cancer Induced by CT26 Cell Line. International Journal of Cancer Management, 18(18), e163536.
Omidiparsa, M., Nazarali, P., Alizadeh, R., & Rezaeinezhad, N. (2025). Effect of high-intensity interval training combined with pomegranate juice supplementation on the granulocyte colony-stimulating factor signaling pathway in an animal model of colorectal cancer induced by CT26 cell line. International Journal of Cancer Management, 18(1), e158597. https://doi.org/10.5812/ijcm-158597
Reguero, M., Gómez de Cedrón, M., Sierra-Ramírez, A., Fernández-Marcos, P. J., Reglero, G., Quintela, J. C., & Ramírez de Molina, A. (2022). Pomegranate extract augments energy expenditure counteracting the metabolic stress associated with high-fat-diet-induced obesity. International Journal of Molecular Sciences, 23(18), 10460.
Reis, J., Massari, M., Marchese, S., Ceccon, M., Aalbers, F. S., Corana, F., ... & Mattevi, A. (2020). A closer look into NADPH oxidase inhibitors: Validation and insight into their mechanism of action. Redox biology, 32, 101466.
Seeram, N. P., Adams, L. S., Henning, S. M., Niu, Y., Zhang, Y., Nair, M. G., & Heber, D. (2005). In vitro antiproliferative, apoptotic and antioxidant activities of punicalagin, ellagic acid and a total pomegranate tannin extract are enhanced in combination with other polyphenols as found in pomegranate juice. The Journal of nutritional biochemistry, 16(6), 360-367.
Seifried, H. E., Anderson, D. E., Fisher, E. I., & Milner, J. A. (2018). A review of the interaction among dietary antioxidants and reactive oxygen species. The Journal of Nutritional Biochemistry, 56, 1–10. https://doi.org/10.1016/j.jnutbio.2017.12.001
Simioni, C., Zauli, G., Martelli, A. M., Vitale, M., Sacchetti, G., Gonelli, A., & Neri, L. M. (2018). Oxidative stress: role of physical exercise and antioxidant nutraceuticals in adulthood and aging. Oncotarget, 9(24), 17181.
Skrzydlewska, E., Sulkowski, S., Koda, M., Zalewski, B., Kanczuga-Koda, L., & Sulkowska, M. (2005). Lipid peroxidation and antioxidant status in colorectal cancer. World journal of gastroenterology: WJG, 11(3), 403.
Sohrab, G., Angoorani, P., Tohidi, M., Tabibi, H., Kimiagar, M., & Nasrollahzadeh, J. (2015). Pomegranate (Punicagranatum) juice decreases lipid peroxidation, but has no effect on plasma advanced glycated end-products in adults with type 2 diabetes: a randomized double-blind clinical trial. Food & nutrition research, 59(1), 28551.
Taghavinia, F., Teymouri, F., Farokhrouz, F., Bagherabad, E. H., Farjami, S., Karimi, E., ... & Shakeri, M. (2022). Nanoliposome-loaded phenolics from Nasturtium officinale improves health parameters in a colorectal cancer mouse model. Animals, 12(24), 3492.
Takiguchi, K., Shimizu, H., Shoda, K., Shiraishi, K., Furuya, S., Hosomura, N., ... & Ichikawa, D. (2023). The expression and role of NADPH Oxidase 2 in colon cancer. Anticancer Research, 43(6), 2601-2608.
Tortora, K., Femia, A. P., Romagnoli, A., Sineo, I., Khatib, M., Mulinacci, N., ... & Caderni, G. (2018). Pomegranate by‐products in colorectal cancer chemoprevention: effects in Apc‐mutated Pirc rats and mechanistic studies in vitro and ex vivo. Molecular nutrition & food research, 62(2), 1700401.
Ungvari, Z., Fekete, M., Varga, P., Lehoczki, A., Fekete, J. T., Ungvari, A., & Győrffy, B. (2025). Overweight and obesity significantly increase colorectal cancer risk: a meta-analysis of 66 studies revealing a 25–57% elevation in risk. Geroscience, 47(3), 3343-3364.
Wu, C., Cheng, M., Li, Y., & Liang, D. (2025). Synergistic power of functional foods and exercise in colorectal cancer control: Targeting metabolism, mitochondrial function, redox homeostasis, exercise performance, neuroimmune signaling, and brain-gut axis crosstalk. Frontiers in Nutrition, 12, 1640092.
Xu, G., Li, Q., Yang, Q., & Yu, H. (2025). The effect of high-intensity interval training on health-related outcomes in obese adolescents: a systematic review and meta-analysis. Frontiers in Physiology, 16, 1609818.
Ye, P., Xi, Y., Huang, Z., & Xu, P. (2020). Linking obesity with colorectal cancer: epidemiology and mechanistic insights. Cancers, 12(6), 1408.
Ye, Y., Lin, H., Wan, M., Qiu, P., Xia, R., He, J., ... & Zheng, G. (2021). The effects of aerobic exercise on oxidative stress in older adults: a systematic review and meta-analysis. Frontiers in physiology, 12, 701151.
Ye, Y., Lin, H., Wan, M., Qiu, P., Xia, R., He, J., ... & Zheng, G. (2021). The effects of aerobic exercise on oxidative stress in older adults: a systematic review and meta-analysis. Frontiers in physiology, 12, 701151.
Yildirim, E. K., & Yildirim, E. (2024). Effects of exercise and pomegranate–black carrot juice mixture on serum mineral and fatty acid levels and some biochemical parameters in sedentary individuals. Applied Sciences, 14(16), 7284.
Zainuddin, A., Susanto, H., & Rosidi, A. (2019). The effect of red pomegranate juice on malondialdehyde and blood lactic acid levels in rats with maximum physical activity. Jurnal Gizi Pangan, 14(2), 77–82. https://doi.org/10.25182/jgp.2019.14.2.77-8.
