The effects of silymarin supplementation on cellular damage and stress indices after an acute aerobic exercise: a randomized, placebo-controlled, double-masked clinical study

doi:10.21203/rs.3.rs-3400083/v2

Download PDF

Research Article

The effects of silymarin supplementation on cellular damage and stress indices after an acute aerobic exercise: a randomized, placebo-controlled, double-masked clinical study

https://doi.org/10.21203/rs.3.rs-3400083/v2

This work is licensed under a CC BY 4.0 License

Version 2

posted

You are reading this latest preprint version

Introduction: Intense physical activity leads to muscle damage associated with increased oxidative stress and changes in antioxidant balance. This study aims to evaluate the effect of silymarin extract supplementation on damage indicators and cellular stress in active men after acute aerobic exercise.

Materials and Methods: Twenty athletic men (average age of 25.09 ± 2.11 years) were placed in two groups of silymarin (n = 10) and placebo (n = 10) in a double-masked design. After 14 days of supplementation, both groups participated in an aerobic exercise protocol. Changes in serum creatine kinase (CK), total antioxidant capacity (TAC), and myeloperoxidase (MPO) levels were measured before and immediately after the workout. The data were analyzed using the analysis of the covariance test at a significancy level of p < 0.05.

Results: The results showed that acute aerobic exercise significantly increased CK and MPO levels in both groups (p ≤ 0.05). However, this increment was lower in the silymarin group compared to the placebo group. In addition, the TAC increased significantly in the silymarin group after two weeks of supplementation compared to the placebo group (p ≤ 0.05).

Conclusion: Based on the present research findings, a 14-day silymarin supplementation likely prevents muscle damage and oxidative stress caused by performing a residual aerobic session in men.

Sports Medicine and Kinesiology

Nutrition & Dietetics

Silymarin

Acute aerobic activity

Creatine kinase

Myeloperoxidase

Total antioxidant capacity

Physical activity and exercise are integral components of a healthy lifestyle, conferring a wide array of physiological and psychological benefits. However, rigorous and intense exercise regimens, including eccentric resistance exercises, strength training, and acute aerobic activities, can induce muscle damage and oxidative stress, potentially undermining the positive effects of exercise (Twist & Eston, 2005; Vargas-Mendoza et al., 2020). This process is often accompanied by an elevation in serum muscle damage indicators, such as creatine kinase (CK), serving as markers of cellular disruption (Jamali Qarakhanlou et al., 2013).

The increase in CK levels following intense physical activities has been widely reported (Amalraj et al., 2020; Delecroix et al., 2017; Jamali Qarakhanlou et al., 2013; Jia et al., 2013; Pepe et al., 2009). Furthermore, even low-intensity exercise can trigger muscle damage and inflammation (Jamali Qarakhanlou et al., 2013; Jia et al., 2013). The act of exercise itself can lead to oxidative stress and alterations in antioxidant activity, with residual activity being recognized as particularly influential in inducing oxidative stress (Jia et al., 2013; Magherini et al., 2019; Pingitore et al., 2015).

Exercise-induced oxidative stress arises from excessive generation of free radicals and the depletion of endogenous antioxidants, compromising antioxidant capacity and leading to oxidative damage of biological macromolecules, including membrane lipids

(Anthony & Saleh, 2013; Marmouzi et al., 2021; Périard et al., 2021; Sharifi-Rad et al., 2020). Imbalances between oxidants and antioxidants may result from decreased antioxidant capacity or the excessive production of oxidants, either endogenous or exogenous in origin (Forman & Zhang, 2021; Negahdary et al., 2015; Sies, 2020). To address these challenges, researchers have sought strategies involving anti-inflammatory and antioxidant compounds to mitigate exercise-induced injury (Atanasov et al., 2021). This is especially pertinent given concerns regarding the adverse effects associated with the improper use of non-steroidal anti-inflammatory drugs (NSAIDs) and certain industrial supplements (Bindu et al., 2020; Davani-Davari et al., 2018; Kushner et al., 2022).

In this context, natural dietary supplements have garnered interest as potential means of addressing exercise-induced oxidative stress. Silymarin, a polyphenolic extract derived from Silybum marianum (milk thistle), has gained attention for its antioxidative and cytoprotective properties (Hekmat-Ardakani et al., 2022; Karimi et al., 2011). Traditionally used in herbal medicine to treat various ailments, silymarin's antioxidant potential and ability to combat free radicals have been extensively studied (Aghemo et al., 2022; Ehrman, 2013; Sharifian et al., 2020). Clinical studies have even suggested that silymarin may possess antioxidant effects comparable to or even superior to vitamin E (Shaker et al., 2010).

The mechanisms underlying silymarin's antioxidative effects are multifaceted, encompassing the scavenging of free radicals, regulation of free radical-producing enzymes, maintenance of mitochondrial electron transport chain integrity, and activation of a range of antioxidant and non-antioxidant enzymes (Surai, 2015; Taleb et al., 2018). Additionally, silymarin's modulation of transcription factors such as Nuclear factor erythroid 2-related factor 2 (NRF2) and Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) contributes to its cellular stress response and vitagen activation (Arafa Keshk et al., 2017; Ehrman, 2013; Shaker et al., 2010; Yardım et al., 2021).

While existing studies have explored silymarin's potential benefits, a comprehensive investigation of its supplementation during acute aerobic exercise remains essential. The present study aims to bridge this gap by examining the effects of silymarin supplementation on serum indicators of muscle damage (CK), oxidative stress (MPO), and total antioxidant capacity (TAC) following an acute aerobic exercise session. In doing so, we seek to enhance our understanding of silymarin's potential role in supporting exercise outcomes and recovery, thus providing valuable insights for practitioners aiming to optimize exercise regimens and manage exercise-induced stress.

2.1 Ethical approval

This research has been approved by the Research and Technology Ethics Committee of Tabriz University of Medical Sciences (TBZMED.REC.1394.149.).

2.2 Subjects

The study's statistical population consisted of active male students. The subjects were randomly selected from 35 participating volunteers through online software (https://www.randomizer.org) and placed in control and experimental groups of ten individuals. Subjects participated in the study voluntarily through invitation. The sample size was determined at a significance level (alpha or type I error) of 0.05% and power (beta or type II error) of 0.8 using MedCal software version 10.0.2.0 for each group.

2.3 Study design

The current research was conducted as a two-group semi-experimental design (experimental and control) in a double-masked manner. First, the athletes were invited to participate in the coordination meeting in the researcher's presence. A complete description of the study goals and measurement methods, instructions on filling out the consent form, and health questionnaires were provided to the athletes. One week before starting the protocol, the subjects' body composition measurements were taken (Table 1). Moreover, the participants' daily diet was surveyed using a 24-hour dietary recall (24HR) questionnaire to check the calorie intake and the energy contribution of macronutrients using the software Nutritionalist IV database (Table 1). Figure 1 illustrates the schematical design of the research.

2.4 Inclusion and exclusion criteria

The criteria for subjects for entering the study included active men aged 22 to 27 who had 3-5 sessions of physical activity during the past six months, with a body fat percentage of 10-15% and maximum oxygen consumption (VO2 max) of 50-55 mL/kg. The exclusion criteria included a history of liver diseases and previous injuries (especially injuries in ankles, back, and knees), allergy and sensitivity to medication, high blood pressure, cardiovascular diseases, consumption of supplements, and antioxidant or anti-inflammatory drugs over the last six months.

2.5 Supplementation

Silymarin capsules were purchased from Isfahan Gol Daru company with a health license number (IRC 1228055713) issued by the General Department of Food Supervision of the Ministry of Health. The supplementation included three capsules of approximately 200 mg of silymarin per day, prescribed in accordance with the person's body weight. All participants were kept blind, unaware of the capsule's content. The subjects in the supplement group took 6 mg of silymarin per kilogram of body weight, and the ones in the placebo group took the same amount of similarly-flavored dextrin for two weeks.

2.6 Exercise protocol

The exercise protocol consisted of running on a treadmill (with an intensity of 65-70% of the heart rate reserve and 0% incline). The basic heart rate of each subject was recorded with a polar heart rate monitor after 10 minutes of rest (in a sitting position). While the maximum heart rate of the subjects was recorded using the heart rate resembling the end of the activity of the Bruce stimulator, the maximum heart rate was obtained through the tape recorder's screen (when the subjects were no longer able to continue the activity). In order to maintain the activity intensity of 65% of the maximum heart rate, Karvonen's method (heart rate reserve formula)- with a percentage equal to the percentage of maximum oxygen consumption (aerobic capacity)- was used. Before performing the exercise protocol, the subjects did stretch exercises for 10 minutes as a warm-up. Then they ran for three minutes on the treadmill with a zero-degree incline (until reaching a heart rate of 120 beats per minute). After this stage, the treadmill speed increased to match the target heart rate (65-70% of the heart rate reserve) within two minutes (2,3). Each subject ran on the treadmill with an approximate intensity of 65% of the heart rate reserve until the voluntary stop. The researchers controlled and recorded the subjects' heart rates and the treadmill's speed until the end of the exercise protocol.

2.7 Blood sampling and laboratory analysis

Blood samples were taken in 4.5 ml from the Median Cubital Vein of the subjects' left arm before and immediately after the training protocol. All samples were taken from 9 am-12 pm, using the same ventilation and ambient light system. Moreover, the subjects maintained a normal diet and refrained from consuming food supplements that affected injury and inflammation 48 hours before the test.

The blood samples were transferred to the laboratory to assess the activity of CK, MPO, and TAC in serum. Then the samples were kept at room temperature (22-25°C) for 15 minutes until coagulated. The samples were centrifuged at 3500 rpm for 10 minutes to isolate the serum. The serum samples were transferred to microtubes and kept at -70°C to measure variables.

2.8 Statistical analysis

For statistical analysis, the normality of data distribution was checked by the Shapiro-Wilk test, and the results normality was shown as mean ± standard deviation. Then, the average changes of each variable were performed using the analysis of covariance test at a significant level of α≤0.05 using SPSS 22 and Excel 2019 software.

All anthropometric and physiological characteristics of the subjects are shown in Table 1. This table shows no statistically significant difference between the studied groups (p>0.05). Therefore, the groups were homogeneous with each other (Table 1).

However, the results of the covariance analysis showed that a session of aerobic exercise significantly increased the levels of CK and MPO instantly after the exercise in the placebo group (p≥0.05). Nevertheless, no significant change was observed in the TAC levels (p>0.05).

The group that received silymarin supplementation displayed a significant increase in all three indicators after the aerobic activity session (p≥0.05) (Table 2).

Furthermore, the comparison between the groups showed that the silymarin group experienced a significant decrease in CK and MPO indices after the test compared to the placebo group (Figures 2 and 3).

In contrast, the TAC index of the supplemented group significantly increased compared to the placebo group (p≥0.05) (Figure 4).

The present study investigated the effects of silymarin extract on damage indicators and cellular stress response in active men following a session of acute aerobic activity. The findings provide valuable insights into the potential benefits of silymarin supplementation in mitigating muscle damage and oxidative stress resulting from intense physical activity. The discussion hereunder elaborates on the study's outcomes and contextualizes them within the existing body of research.

4.1 Muscle Damage and Silymarin Supplementation

The study's results indicated an immediate increase in muscle damage indicators following acute aerobic physical activity. This finding aligns with previous research suggesting that high-intensity activities can cause disruptions in cell membranes, including sarcolemma rupture and plasma membrane instability (Brancaccio et al., 2010). Remarkably, the group supplemented with silymarin exhibited a significant reduction in immediate muscle damage, highlighting the potential protective effect of silymarin against mechanical-metabolic pressure on membranes induced by exercise. These findings are in line with Sharifian et al. (2020), who observed decreased muscle damage index (CK) in wrestlers after long-term silymarin supplementation (Sharifian et al., 2020). The stabilization of cell membranes through increased endogenous antioxidant reserves and cleansing of free bases likely contributed to this reduction (Shaker et al., 2010).

Nonetheless, the inconsistency between the findings of Sabzevarizadeh and Najafzadeh (2012) and the present study underscores the influence of various factors such as subject type, supplementation method, and amount (Sabzevarizadeh & Najafzadeh, 2012). Moreover, the divergence in creatine kinase response could be attributed to differences in the type, duration, and intensity of physical activity, which impact the magnitude and duration of enzyme secretion (Brancaccio et al., 2010).

4.2 Oxidative Stress and Silymarin Supplementation

The study revealed a decrease in total antioxidant capacity (TAC) and an increase in oxidative stress index (MPO) after acute aerobic exercise, consistent with findings from previous studies (Boukazoula & Ayari, 2022; Fonseca et al., 2016; Holz et al., 2015; Jafari et al., 2011; Rostami & Jafari, 2012). Notably, silymarin supplementation for 14 days prevented the decline in TAC and mitigated the undesirable increase in MPO activity. This aligns with previous research indicating that silymarin supplementation enhances antioxidant enzymes and prevents oxidative indices from rising (Aktaş & Özgöçmen, 2020; Al-Enazi, 2013; Beydilli et al., 2015; Cristofalo et al., 2013; Sajedianfard et al., 2014). The antioxidative effects of silymarin, including inhibition of lipid peroxidation and maintenance of cell membrane integrity against oxidative damage, contribute to its protective role against exercise-induced oxidative stress (Nencini et al., 2007; Surai, 2015).

The modulation of oxidative and inflammatory responses by silymarin could be influenced by the dose-dependent effects of supplementation (Sharma et al., 2012). Complex interactions, such as those observed in the current study, highlight the multifaceted nature of oxidative stress processes induced by exercise, encompassing factors ranging from oxygen leakage to cellular metabolism and calcium ion homeostasis (Fisher-Wellman & Bloomer, 2009; Hargreaves & Spriet, 2020; Jafari et al., 2011; Rostami & Jafari, 2012).

4.3 Mechanisms Underlying Silymarin's Effects

The beneficial effects of silymarin are attributed to its multifunctional properties, including its structural resemblance to steroid hormones, which enables it to influence RNA polymerase I and rRNA transcription, leading to enhanced protein synthesis and cell membrane integrity (Beydilli et al., 2015; Hodges & Smeets, 2015; Jafari et al., 2011). Silymarin's direct actions, such as scavenging free bases, chelating bivalent elements, preventing Fenton reactions, and activating protective molecules like heat shock proteins, contribute to its antioxidant properties (Taleb et al., 2018).

Additionally, silymarin's impact on antioxidant enzyme activity, modulation of redox balance, and activation of Nrf2 highlight its role in protecting cell membranes and structures from oxidative damage (Hodges & Smeets, 2015; Surai, 2015). The findings of this study collectively support the notion that silymarin's effects extend beyond its antioxidative properties, encompassing mechanisms that contribute to cellular integrity and resilience against the stressors induced by exercise.

4.4 Limitations and Future Directions

While the study presents valuable insights into the potential benefits of silymarin supplementation, certain limitations warrant consideration. The duration, dosage, and administration method of silymarin supplementation may influence the observed outcomes. Moreover, variations in subject populations and the type of exercise could contribute to discrepancies between studies. Future research could explore optimal dosages and durations of silymarin supplementation to further elucidate its protective effects against exercise-induced muscle damage and oxidative stress. Mechanistic studies dissecting the interplay between silymarin and various cellular pathways are also warranted to provide a comprehensive understanding of its mode of action.

In summary, this study's findings conclude that 14-day consumption of silymarin will prevent adverse changes in oxidative stress index and muscle damage caused by intense aerobic activity via increasing the total antioxidant capacity. Therefore, noting the precautionary aspects, active people and athletes can take silymarin supplementation to prevent the loss of antioxidant capacity, oxidative stress, and consequent inflammations.

Funding

This work was supported by Nutrition Research Center of Tabriz University of Medical Sciences [grant no. 61865].

Competing Interests

The authors have no competing interests to declare that are relevant to the content of this article.

Authors' contributions

All authors contributed to the study conceptualization and formal analysis. The study design and methodology were devised by Bahram Jamali Gharakhanlou and Mohammad Reza Shiri-Shahsavar. Material preparation, data curation, and investigation was done by Bahram Jamali Gharakhanlou, Akram Amaghani, and Shahabaddin Solaimanian. The software work was carried out by Bahram Jamali Gharakhanlou, Mohammad Reza Shiri-Shahsavar, and Bita Rahmani. The manuscript's original draft was written by Bahram Jamali Gharakhanlou, Bita Rahmani, and Shahabaddin Solaimanian, and was reviewed and edited by Bita Rahmani and Shahabaddin Solaimanian. Funding was acquired by Bahram Jamali Gharakhanlou. The project was administered by Bahram Jamali Gharakhanlou, and all steps were supervised and validated by Mohammad Reza Shiri-Shahsavar and Bahram Jamali Gharakhanlou. All authors have read and approved the final manuscript.

Data Availability

All data generated or analyzed during this study are included n this published article [and its supplementary information files].

Ethics approval

The study was performed in line with the guidelines and principles of the Declaration of Helsinki. The study protocol approval was granted by the Research and Technology Ethics Committee of Tabriz University of Medical Sciences (TBZMED.REC.1394.149.).

Consent to participate

Informed consent was obtained from all individual participants included in the study, prior to the conduction of the research.

Consent to publish

The authors affirm that human research participants provided informed consent for publication of information provided in Table 1, before conducting the research.

Acknowledgments

We would like to express our gratitude to the Nutrition Research Center of Tabriz University of Medical Sciences, for their valuable support throughout this study.

Abdel-Latif, H. M. R., Shukry, M., Noreldin, A. E., Ahmed, H. A., El-Bahrawy, A., Ghetas, H. A., & Khalifa, E. (2022). Milk thistle (Silybum marianum) extract improves growth, immunity, serum biochemical indices, antioxidant state, hepatic histoarchitecture, and intestinal histomorphometry of striped catfish, Pangasianodon hypophthalmus. Aquaculture.
Aghemo, A., Alekseeva, O. P., Angelico, F., Bakulin, I. G., Bakulina, N. V, Bordin, D., Bueverov, A. O., Drapkina, O. M., Gillessen, A., Kagarmanova, E. M., Korochanskaya, N. V, Kucheryavii, U. A., Lazebnik, L. B., Livzan, M. A., Maev, I. V, Martynov, A. I., Osipenko, M. F., Sas, E. I., Starodubova, A., … Yakovlev, A. A. (2022). Role of silymarin as antioxidant in clinical management of chronic liver diseases: a narrative review. Annals of Medicine, 54(1), 1548–1560. https://doi.org/10.1080/07853890.2022.2069854
Aktaş, I., & Özgöçmen, M. (2020). The treatment effect of silymarin on heart damage in rats. Annals of Medical Research, 27, 948. https://doi.org/10.5455/annalsmedres.2019.10.643
Al-Enazi, M. (2013). Neuroprotective Effect of Silymarin by Modulation of Endogenous Biomarkers in Streptozotocin Induced Painful Diabetic Neuropathy. British Journal of Pharmacology and Toxicology, 4, 110–120. https://doi.org/10.19026/bjpt.4.5372
Amalraj, A., Divya, C., & Gopi, S. (2020). The Effects of Bioavailable Curcumin (Cureit) on Delayed Onset Muscle Soreness Induced By Eccentric Continuous Exercise: A Randomized, Placebo-Controlled, Double-Blind Clinical Study. Journal of Medicinal Food, 23(5), 545–553. https://doi.org/10.1089/jmf.2019.4533
Anthony, K. P., & Saleh, M. A. (2013). Free Radical Scavenging and Antioxidant Activities of Silymarin Components. Antioxidants (Basel, Switzerland), 2(4), 398–407. https://doi.org/10.3390/antiox2040398
Arafa Keshk, W., Zahran, S. M., Katary, M. A., & Abd-Elaziz Ali, D. (2017). Modulatory effect of silymarin on nuclear factor-erythroid-2-related factor 2 regulated redox status, nuclear factor-κB mediated inflammation and apoptosis in experimental gastric ulcer. Chemico-Biological Interactions, 273, 266–272. https://doi.org/https://doi.org/10.1016/j.cbi.2017.06.022
Atanasov, A. G., Zotchev, S. B., Dirsch, V. M., Orhan, I. E., Banach, M., Rollinger, J. M., Barreca, D., Weckwerth, W., Bauer, R., Bayer, E. A., Majeed, M., Bishayee, A., Bochkov, V., Bonn, G. K., Braidy, N., Bucar, F., Cifuentes, A., D’Onofrio, G., Bodkin, M., … Taskforce, the I. N. P. S. (2021). Natural products in drug discovery: advances and opportunities. Nature Reviews Drug Discovery, 20(3), 200–216. https://doi.org/10.1038/s41573-020-00114-z
Beydilli, H., Yilmaz, N., Cetin, E. S., Topal, Y., Celik, O. I., Sahin, C., Topal, H., Cigerci, I. H., & Sozen, H. (2015). Evaluation of the protective effect of silibinin against diazinon induced hepatotoxicity and free-radical damage in rat liver. Iranian Red Crescent Medical Journal, 17(4), e25310. https://doi.org/10.5812/ircmj.17(4)2015.25310
Bindu, S., Mazumder, S., & Bandyopadhyay, U. (2020). Non-steroidal anti-inflammatory drugs (NSAIDs) and organ damage: A current perspective. Biochemical Pharmacology, 180, 114147. https://doi.org/10.1016/j.bcp.2020.114147
Boukazoula, F., & Ayari, D. (2022). Effect of milk thistle (Silybum marianum) supplementation on the serum levels of oxidative stress markers in male half marathon athletes. Biomarkers: Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals, 27(5), 461–469. https://doi.org/10.1080/1354750X.2022.2056921
Brancaccio, P., Lippi, G., & Maffulli, N. (2010). Biochemical markers of muscular damage. Clinical Chemistry and Laboratory Medicine, 48(6), 757–767. https://doi.org/10.1515/CCLM.2010.179
Cristofalo, R., Bannwart-Castro, C. F., Magalhães, C. G., Borges, V. T. M., Peraçoli, J. C., Witkin, S. S., & Peraçoli, M. T. (2013). Silibinin attenuates oxidative metabolism and cytokine production by monocytes from preeclamptic women. Free Radical Research, 47(4), 268–275. https://doi.org/10.3109/10715762.2013.765951
Dadban-Shahamat, M., Shakki, M., & Hashemi-Chashmi, S. Z. (2021). The Effect of High-Intensity Intermittent Exercise with Silymarin Supplementation on Liver Enzymes in Male Rats of Fatty Liver Model. J Isfahan Med Sch, 38(606), 989–995. https://doi.org/10.22122/jims.v38i606.13642
Davani-Davari, D., Karimzadeh, I., Ezzatzadegan-Jahromi, S., & Sagheb, M. M. (2018). Potential Adverse Effects of Creatine Supplement on the Kidney in Athletes and Bodybuilders. Iranian Journal of Kidney Diseases, 12(5), 253–260.
Delecroix, B., Abaïdia, A. E., Leduc, C., Dawson, B., & Dupont, G. (2017). Curcumin and Piperine Supplementation and Recovery Following Exercise Induced Muscle Damage: A Randomized Controlled Trial. Journal of Sports Science & Medicine, 16(1), 147–153.
Ehrman,
Fisher-Wellman, K., & Bloomer, R. J. (2009). Acute exercise and oxidative stress: a 30 year history. Dynamic Medicine, 8(1), 1. https://doi.org/10.1186/1476-5918-8-1
Fonseca, R., Kenny, D., Mcgivney, B., Murphy, B., Hill, E. W., & Katz, L. (2016). Effect of training on plasma myeloperoxidase concentrations measured before and following intense exercise in Thoroughbred racehorses. Comparative Exercise Physiology, 12, 1–10. https://doi.org/10.3920/CEP150028
Forman, H. J., & Zhang, H. (2021). Targeting oxidative stress in disease: promise and limitations of antioxidant therapy. Nature Reviews Drug Discovery, 20(9), 689–709. https://doi.org/10.1038/s41573-021-00233-1
Hargreaves, M., & Spriet, L. L. (2020). Skeletal muscle energy metabolism during exercise. Nature Metabolism, 2(9), 817–828. https://doi.org/10.1038/s42255-020-0251-4
Hekmat-Ardakani, A., Morshed-Behbahani, B., Rahimi-Ardabili, H., Ayati, M. H., & Namazi, N. (2022). The effects of dietary supplements and natural products targeting glucose levels: an overview. Critical Reviews in Food Science and Nutrition, 1–30. https://doi.org/10.1080/10408398.2022.2028716
Hodges, P. W., & Smeets, R. J. (2015). Interaction between pain, movement, and physical activity: short-term benefits, long-term consequences, and targets for treatment. The Clinical Journal of Pain, 31(2), 97–107. https://doi.org/10.1097/AJP.0000000000000098
Holz, O., Roepcke, S., Watz, H., Tegtbur, U., Lahu, G., & Hohlfeld, J. M. (2015). Constant-load exercise decreases the serum concentration of myeloperoxidase in healthy smokers and smokers with COPD. International Journal of Chronic Obstructive Pulmonary Disease, 10, 1393–1402. https://doi.org/10.2147/COPD.S83269
Jafari, A., rasoul Zekri, Dehghan, G., & Malekirad, A. A. (2011). Effect of short-term garlic extract supplementation on oxidative stress and inflammatory indices in non-athlete men after an aerobic exercise. Journal of Cell & Tissue, 2, 25–33.
Jamali Qarakhanlou, B., Amaghani, A., & Tofighi, A. (2013). Effect of Single Stage Caffeine Supplementation on CK and IL-6 Responses in Non-Active Male after an Exhaustive Aerobic Exercise. Medical Journal of Tabriz University of Medical Sciences and Health Services, 35, 18–25.
Jia, R., Cao, L., Du, J., Xu, P., Jeney, G., & Yin, G. (2013). The protective effect of silymarin on the carbon tetrachloride (CCl4)-induced liver injury in common carp (Cyprinus carpio). In Vitro Cellular & Developmental Biology. Animal, 49(3), 155–161. https://doi.org/10.1007/s11626-013-9587-3
Karimi, G., Vahabzadeh, M., Lari, P., Rashedinia, M., & Moshiri, M. (2011). “Silymarin”, a promising pharmacological agent for treatment of diseases. Iranian Journal of Basic Medical Sciences, 14(4), 308–317.
Khazaei, R., Seidavi, A., & Bouyeh, M. (2022). A review on the mechanisms of the effect of silymarin in milk thistle (Silybum marianum) on some laboratory animals. Veterinary Medicine and Science, 8(1), 289–301. https://doi.org/10.1002/vms3.641
Kushner, P., McCarberg, B. H., Grange, L., Kolosov, A., Haveric, A. L., Zucal, V., Petruschke, R., & Bissonnette, S. (2022). The use of non-steroidal anti-inflammatory drugs (NSAIDs) in COVID-19. Npj Primary Care Respiratory Medicine, 32(1), 35. https://doi.org/10.1038/s41533-022-00300-z
Machado, M., Koch, A. J., Willardson, J. M., dos Santos, F. C., Curty, V. M., & Pereira, L. N. (2010). Caffeine does not augment markers of muscle damage or leukocytosis following resistance exercise. International Journal of Sports Physiology and Performance, 5(1), 18–26. https://doi.org/10.1123/ijspp.5.1.18
Magherini, F., Fiaschi, T., Marzocchini, R., Mannelli, M., Gamberi, T., Modesti, P. A., & Modesti, A. (2019). Oxidative stress in exercise training: the involvement of inflammation and peripheral signals. Free Radical Research, 53(11–12), 1155–1165. https://doi.org/10.1080/10715762.2019.1697438
Marmouzi, I., Bouyahya, A., Ezzat, S. M., El Jemli, M., & Kharbach, M. (2021). The food plant Silybum marianum (L.) Gaertn.: Phytochemistry, Ethnopharmacology and clinical evidence. Journal of Ethnopharmacology, 265, 113303. https://doi.org/10.1016/j.jep.2020.113303
Negahdary, M., Bezhgi, M., & Ajdary, M. (2015). Effects of Silymarin on Oxidative Stress Markers in Rats Treated with Magnesium Oxide Nanoparticles. Annual Research \& Review in Biology, 5, 254–261.
Nencini, C., Giorgi, G., & Micheli, L. (2007). Protective effect of silymarin on oxidative stress in rat brain. Phytomedicine: International Journal of Phytotherapy and Phytopharmacology, 14(2–3), 129–135. https://doi.org/10.1016/j.phymed.2006.02.005
Pepe, H., Balcı, Ş. S., Revan, S., Akalın, P. P., & Kurtoğlu, F. (2009). Comparison of oxidative stress and antioxidant capacity before and after running exercises in both sexes. Gender Medicine, 6 4, 587–595.
Périard, J. D., Eijsvogels, T. M. H., & Daanen, H. A. M. (2021). Exercise under heat stress: thermoregulation, hydration, performance implications, and mitigation strategies. Physiological Reviews, 101(4), 1873–1979. https://doi.org/10.1152/physrev.00038.2020
Pingitore, A., Lima, G. P. P., Mastorci, F., Quinones, A., Iervasi, G., & Vassalle, C. (2015). Exercise and oxidative stress: potential effects of antioxidant dietary strategies in sports. Nutrition (Burbank, Los Angeles County, Calif.), 31(7–8), 916–922. https://doi.org/10.1016/j.nut.2015.02.005
Rostami, A. R., & Jafari, A. (2012). Effect of short-term coenzyme Q10 supplementation on oxidative stress index and total antioxidant capacity of serum in inactive men. Medical Journal of Tabriz University of Medical Sciences and Health Services, 34(3), 46–51.
Sabzevarizadeh, M., & Najafzadeh, H. (2012). Comparison Effect of Silymarin and Vitamin C on Liver Function in Myoglobinuric Status in Rats. J World Appl Sci J., 17(2), 228–232.
Sajedianfard, J., Nazifi, S., & Shamsaei, H. A. (2014). The effects of oral administration of different doses of hydroalcoholic extract of silymarin on status of serum trace elements. American Journal of Animal and Veterinary Sciences, 9(3). https://doi.org/10.3844/ajavsp.2014.170.176
Shaker, E., Mahmoud, H., & Mnaa, S. (2010). Silymarin, the antioxidant component and Silybum marianum extracts prevent liver damage. Food and Chemical Toxicology: An International Journal Published for the British Industrial Biological Research Association, 48(3), 803–806. https://doi.org/10.1016/j.fct.2009.12.011
Sharifi-Rad, M., Anil Kumar, N. V, Zucca, P., Varoni, E. M., Dini, L., Panzarini, E., Rajkovic, J., Tsouh Fokou, P. V., Azzini, E., Peluso, I., Prakash Mishra, A., Nigam, M., El Rayess, Y., Beyrouthy, M. El, Polito, L., Iriti, M., Martins, N., Martorell, M., Docea, A. O., … Sharifi-Rad, J. (2020). Lifestyle, Oxidative Stress, and Antioxidants: Back and Forth in the Pathophysiology of Chronic Diseases. Frontiers in Physiology, 11. https://doi.org/10.3389/fphys.2020.00694
Sharifian, M., Behpour, N., Mohajerani, H. R., & Darabi, F. (2020). Effect of four weeks supplementation with silybum marianum on indicators of serum muscle damage in incremental training wrestlers. Razi Journal of Medical Sciences, 27, 75–84.
Sharma, R., Siddiqi, N. J., & Sharma, B. (2012). Protective Effect of Silymarin on Human Erythrocyte Against Tert-butyl Hydroperoxide Induced Oxidative Stress in vitro. American Journal of Biochemistry and Molecular Biology, 2, 167–174.
Sies, H. (2020). Oxidative Stress: Concept and Some Practical Aspects. Antioxidants (Basel, Switzerland), 9(9). https://doi.org/10.3390/antiox9090852
Soleimani, V., Delghandi, P. S., Moallem, S. A., & Karimi, G. (2019). Safety and toxicity of silymarin, the major constituent of milk thistle extract: An updated review. Phytotherapy Research: PTR, 33(6), 1627–1638. https://doi.org/10.1002/ptr.6361
Surai, P. F. (2015). Silymarin as a Natural Antioxidant: An Overview of the Current Evidence and Perspectives. Antioxidants (Basel, Switzerland), 4(1), 204–247. https://doi.org/10.3390/antiox4010204
Tabaa, M. M. El, Aboalazm, H. M., Shaalan, M., & Khedr, N. F. (2022). Silymarin constrains diacetyl-prompted oxidative stress and neuroinflammation in rats: involvements of Dyn/GDNF and MAPK signaling pathway. Inflammopharmacology, 30(3), 961–980. https://doi.org/10.1007/s10787-022-00961-9
Taleb, A., Ahmad, K. A., Ihsan, A. U., Qu, J., Lin, N., Hezam, K., Koju, N., Hui, L., & Qilong, D. (2018). Antioxidant effects and mechanism of silymarin in oxidative stress induced cardiovascular diseases. Biomedicine & Pharmacotherapy, 102, 689–698. https://doi.org/https://doi.org/10.1016/j.biopha.2018.03.140
Twist, C., & Eston, R. (2005). The effects of exercise-induced muscle damage on maximal intensity intermittent exercise performance. European Journal of Applied Physiology, 94(5–6), 652–658. https://doi.org/10.1007/s00421-005-1357-9
Vargas-Mendoza, N., Ángeles-Valencia, M., Madrigal-Santillán, E. O., Morales-Martínez, M., Tirado-Lule, J. M., Solano-Urrusquieta, A., Madrigal-Bujaidar, E., Álvarez-González, I., Fregoso-Aguilar, T., Morales-González, Á., & Morales-González, J. A. (2020). Effect of Silymarin Supplementation on Physical Performance, Muscle and Myocardium Histological Changes, Bodyweight, and Food Consumption in Rats Subjected to Regular Exercise Training. International Journal of Molecular Sciences, 21(20). https://doi.org/10.3390/ijms21207724
Yardım, A., Kucukler, S., Özdemir, S., Çomaklı, S., Caglayan, C., Kandemir, F. M., & Çelik, H. (2021). Silymarin alleviates docetaxel-induced central and peripheral neurotoxicity by reducing oxidative stress, inflammation and apoptosis in rats. Gene, 769, 145239. https://doi.org/10.1016/j.gene.2020.145239

Table 1

Participant characteristics. The data are presented as mean ± SD.
	Placebo Group (n = 10)	Silymarin Group (n = 10)	p- value
Height (cm)	178.89 ± 6.29	175.28 ± 6.04	0.16
Weight (kg)	71.05 ± 5.86	70.44 ± 9.87	0.31
BMI (kg/m2)	21.08 ± 1.58	22.74 ± 2.22	0.48
Body fat percentage (%)	13.76 ± 1.70	13.66 ± 2.35	0.32
VO2max(ml/kg^− 1·min^− 1)	49.88 ± 3.38	50.01 ± 6.48	0.19
Systolic blood pressure (mm Hg)	121 ± 11	118 ± 17	0.46
Diastolic blood pressure (mm Hg)	84 ± 0.5	83 ± 0.7	0.27
Heart rate (beats per minute)	71 ± 5	69 ± 4	0.22
Energy Expenditure (Kcal/ per day)	3118.02 ± 118.47	3254.83 ± 139.49	0.19

Table 2

Mean changes of serum CK, MPO, and TAC during an exhaustive aerobic exercise. * indicates significance compared to pre-test values (p > 0.05)
		Placebo Group			Silymarin Group
	Pre test	Post test	p-value	Pre test	Post test	p-value
CK (IU/L)	93.27 ± 17.12	220.62 ± 82.44	0.011*	92.17 ± 16.71	180.36 ± 75.06	0.024*
MPO (ng/Ml)	3.81 ± 1.35	4.89 ± 1.86	0.021*	3.68 ± 1.59	4.35 ± 0.65	0.034*
TAC (mmol/L)	1.81 ± 0.314	1.89 ± 0.562	0.168	1.78 ± 0.369	2.35 ± 0.525	0.002*

Download PDF

Version 2

posted

You are reading this latest preprint version

The effects of silymarin supplementation on cellular damage and stress indices after an acute aerobic exercise: a randomized, placebo-controlled, double-masked clinical study

Status:

Version 2

Abstract

Figures

1. Introduction

2. Materials and Methods

3. Results

4. Discussion

5. Conclusion

Declarations

References

Tables

Status:

Version 2