Effects of Endurance Training and Tribulus terrestris Extract on Oxidative Stress and Apoptosis Markers in the Liver Tissues of Rats Exposed to Arsenic

Document Type : Research Paper


1 Department of Sport Physiology, Central Tehran Branch, Islamic Azad University, Tehran, Iran

2 Department of Exercise Physiology, Central Tehran Branch, Islamic Azad University, Tehran, Iran.

3 Department of Exercise Physiology, Marvdasht Branch, Islamic Azad University, Marvdasht, Iran


Introduction: Arsenic (As) is a toxic metal, which causes disorders in various tissues of the body, including the liver. Studies have shown that exercise and herbs such as Tribulus terrestris (T) have antioxidant effects on some diseases. The present study aimed to investigate the effects of endurance training (ET) and T extract on oxidative stress and apoptosis markers in the liver tissues of rats exposed to As. Methods: This experimental study was conducted on 49 rats, which were randomly assigned into seven groups of control, As, As with 5 mg/kg of T extract (As+T5), As with 10 mg/kg of T extract (As+T10), As with ET, As with ET and 5 mg/kg of T extract (As+ET+T5), and As with ET and 10 mg/kg of T extract (As+ET+T10). For eight weeks, study groups 2-6 consumed sodium arsenite (68 mg/l per day) dissolved in drinking water, and groups 5-7 ran on a treadmill five sessions per week (30 minutes per session) at the speed of 23 meters per minute. Results: Exposure to As significantly increased O-6-methylguanine-DNA methyltransferase (MGMT), cytochrome C, malondialdehyde (MDA), and prooxidant-antioxidant balance (PAB), while decreasing hepatic adenosine triphosphate (ATP) (P=0.001). Training and T extract consumption reduced the concentration of MGMT, cytochrome C, MDA, and PAB, while increasing the hepatic ATP concentration (P=0.001). The T extract at the dose of 10 mg/kg could increase the ATP concentration and decrease cytochrome C, MDA, and PAB more significantly in the liver tissues compared to the dose of 5 mg/kg (P=0.001). In addition, the interactive effects of training and T extract consumption were significant on the reduction of MGMT, cytochrome C, MDA, and PAB concentrations and increasing the hepatic ATP concentration in the rats poisoned with As (P=0.001). Conclusion: According to the results, endurance training with the consumption of Tribulus terrestris extract could inhibit oxidative stress and apoptosis, thereby exerting protective effects on liver tissues against arsenic poisoning. Therefore, these interventions could effectively diminish the effects of arsenic induction on liver tissues. 


1. Hu Y, Li J, Lou B, Wu R, Wang G, Lu C, et al. The role of reactive oxygen species in arsenic toxicity. Biomolecules. 2020;10(2):240.
2. Jahangirnejad R, Goudarzi M, Kalantari H, Najafzadeh H, Rezaei M. Subcellular Organelle Toxicity Caused by Arsenic Nanoparticles in Isolated Rat Hepatocytes. Int J Occup Env Med. 2020;11(1):1614–41.
3. Kalantari H, Houshmand G, Hasanvand A, Kalantar M, Goudarzi M, Haghighian HK. Ameliorative effects of red lentil extract on sodium arsenite-induced oxidative stress in rats. Jundishapur J Nat Pharm Prod. 2017;12(3): e64309. 4. Chang C-Y, Guo H-R, Tsai W-C, Yang K-L, Lin L-C, Cheng T-J, et al. Subchronic arsenic exposure induces anxiety-like behaviors in normal mice and enhances depression-like behaviors in the chemically induced mouse model of depression. Biomed Res Int. 2015;1-12.
5. Qu W, Bortner CD, Sakurai T, Hobson MJ, Waalkes MP. Acquisition of apoptotic resistance in arsenic-induced malignant transformation: role of the JNK signal transduction pathway. Carcinogenesis. 2002;23(1):151–9.
6. Martinez VD, Vucic EA, Adonis M, Gil L, Lam WL. Arsenic biotransformation as a cancer promoting factor by inducing DNA damage and disruption of repair mechanisms. Mol Biol Int. 2011;1-11.
7. Fard HH, Hosseini SA, Azarbayjani MA, Nikbakht M. The effect of interval training with selenium consumption on gene expression of caspase-3 and cyclin-d in liver tissue of cadmium-exposed rats. Jundishapur J Heal Sci. 2020; 11(2):e88598.
8. Homayonfard H, Hosseini SA, Azarbayjani MA, Nikbakht M. Antiapoptotic effects of continuous training and selenium consumption on the liver tissue of cadmium-exposed rats. Middle East J Rehabil Heal. 2019 ; 6(3):e91278. 9. Sun B-F, Wang Q-Q, Yu Z-J, Yu Y, Xiao C-L, Kang C-S, et al. Exercise prevents memory impairment induced by arsenic exposure in mice: implication of hippocampal BDNF and CREB. PLoS One. 2015; 10(9): e0137810.
10. Farzanegi P, Saberi S, Fakharian A, Rasaee MJ, Dabidi Roshan V. Combined effects of Curcuma longa and exercise training on kidney and spleen tissue levels of glutathione peroxidase and protein carbonyl in rats exposed to lead. Pathobiol Res. 2012;15(3):49–62.
11. O’Mahony Carey S. Psychoactive substances: a guide to ethnobotanical plants and herbs, synthetic chemicals, compounds and products. 2014;
12.Semerdjieva IB, Zheljazkov VD. Chemical constituents, biological properties, and uses of Tribulus terrestris: A Review. Nat Prod Commun. 2019;14(8):1–26.
13. Yadav HN, Sharma US, Singh S, Gupta YK. Effect of Tribulus terrestris in mercuric chloride-induced renal accumulation of mercury and nephrotoxicity in rat. J Adv Pharm Technol Res. 2019;10(3): 132–137. 
14. El-Shaibany A, Molham A-H, Al-Tahami B, Al-Massarani S. Anti-hyperglycaemic activity of Tribulus terrestris L aerial part extract in glucose-loaded normal rabbits. Trop J Pharm Res. 2015;14(12):2263–8.
15. Kaushik J, Tandon S, Bhardwaj R, Kaur T, Singla SK, Kumar J, et al. Delving into the Antiurolithiatic potential of Tribulus terrestris extract through–In Vivo Efficacy and Preclinical Safety investigations in Wistar Rats. Sci Rep. 2019;9(1):1–13.
16. Azam F, Munier S, Batoo M, Ahmad B, Abbas G. A review on advancements in ethnomedicine and phytochemistry of Tribulus terrestris–a plant with multiple health benefits. Int J Biosci. 2019;14(1):21–37.
17. Santos HO, Howell S, Teixeira FJ. Beyond Tribulus (Tribulus terrestris L.): The effects of phytotherapics on testosterone, sperm and prostate parameters. J Ethnopharmacol. 2019; 392-405.
18. Bikashvili T, Lordkipanidze T, Gogichaishvili N, Pochkhidze N. Effect of arsenic exposed on behavior of rats of various age groups. Georgian Med News. 2017;(264):119–26.
19. Nishchal BS, Rai S, Prabhu MN, Ullal SD, Rajeswari S, Gopalakrishna HN. Effect of Tribulus terrestris on haloperidol-induced catalepsy in mice. Indian J Pharm Sci. 2014;76(6): 564–567. PMID: 25593394
20. Chae C-H, Treadmill exercise suppresses muscle cell apoptosis by increasing nerve growth factor levels and stimulating p-phosphatidylinositol 3-kinase activation in the soleus of diabetic rats. J Physiol Biochem. 2011;67(2):235–41.
21. Wai KM, Umezaki M, Mar O, Umemura M, Watanabe C. Arsenic exposure through drinking Water and oxidative stress Status: A cross-sectional study in the Ayeyarwady region, Myanmar. J Trace Elem Med Biol. 2019;54:103–9.
22. Steinhorn B, Sorrentino A, Badole S, Bogdanova Y, Belousov V, Michel T. Chemogenetic generation of hydrogen peroxide in the heart induces severe cardiac dysfunction. Nat Commun. 2018;9(1):4044.
23. Guo H, Liu H, Wu H, Cui H, Fang J, Zuo Z, et al. Nickel Carcinogenesis Mechanism: DNA Damage. Int J Mol Sci. 2019;20(19):4690.
24.Nocella C, Cammisotto V, Pigozzi F, Borrione P, Fossati C, D’Amico A, et al. Impairment between oxidant and antioxidant systems: short-and long-term implications for athletes’ health. Nutrients. 2019;11(6):1353.
25. Soares JP, Silva AM, Oliveira MM, Peixoto F, Gaivão I, Mota MP. Effects of combined physical exercise training on DNA damage and repair capacity: role of oxidative stress changes. Age (Omaha). 2015;37(3):61.
26. Siu PM, Pei XM, Teng BT, Benzie IF, Ying M, Wong SH. Habitual exercise increases resistance of lymphocytes to oxidant‐induced DNA damage by upregulating expression of antioxidant and DNA repairing enzymes. Exp Physiol. 2011;96(9):889–906.
27. Qari SH, El-Assouli SM. Evaluation of cytological and genetic effects of Tribulus terrestris fruit aqueous extract on cultured human lymphocytes. Saudi J Biol Sci. 2019;26(1):91–95.
28. Alzahrani S, Ezzat W, Elshaer RE, Abd El-Lateef AS, Mohammad HMF, Elkazaz AY, et al. Standarized Tribulus terrestris extract protects against rotenone-induced oxidative damage and nigral dopamine neuronal loss in mice. J Physiol Pharmacol. 2018;69(6): 979-994.
29. Zhang H, Tong W-T, Zhang C-R, Li J-L, Meng H, Yang H-G, et al. Gross saponin of Tribulus terrestris improves erectile dysfunction in type 2 diabetic rats by repairing the endothelial function of the penile corpus cavernosum. Diabetes, Metab Syndr Obes Targets Ther. 2019;12: 1705–1716.