Iranian Journal of Medical Sciences

Document Type : Original Article(s)


1 Department of Radiologic Technology, Faculty of Paramedicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

2 Medicinal Plant Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

3 Cellular and Molecular Research Center, Department of Anatomical Sciences, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

4 Department of Physiology, Pharmacology and Medical Physics, Faculty of Medicine, Qom University of Medical Sciences, Qom, Iran



Background: Cell phone and Ultra-High Frequency (UHF) waves produce oxidative stress and cause testicular toxicity. This investigation was directed to evaluate the effectiveness of Rosmarinic Acid (RA) against oxidative stress caused by UHF radiation in rats.
Methods: Forty-two male Wistar rats were divided into six groups. The control received 5 mL normal saline (0.9% NaCl) by gavage, the cell phone group received 915 MHz, the UHF waves group just received 2450 MHz, the RA/cell phone group received RA plus 915 MHz, RA/UHF waves group received RA plus 2450 MHz, and RA just received RA (20 mg/kg). After 30 days of consecutive radiation, the biochemical and histopathological parameters of their testes were measured. Statistical comparison was made using one-way ANOVA followed by Tukey’s post hoc test.
Results: Cell phone and UHF wave radiation significantly diminished the activity of antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase, and glutathione content (P<0.001). On the opposite, UHF significantly increased oxidative stress indices including malondialdehyde level, nitric oxide level, and protein carbonyl content (P<0.001). UHF also significantly reduced the number of Sertoli cells, spermatogonia, primary spermatocyte, epithelial height, and seminiferous tubular and luminal diameters (P<0.001). RA, as an effective antioxidant, reverses the above-mentioned harms and moderates the adverse effects of UHF on the testes of rats by significantly diminishing the oxidative stress indices and antioxidant enzyme rise and improving the histological parameters (P<0.001).
Conclusion: RA can protect the testes of rats from UHF-induced toxicity by reducing oxidative stress. RA as a food supplement might be useful for protecting humans exposed to UHF environmental contamination.


  1. Uttara B, Singh AV, Zamboni P, Mahajan RT. Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options. Curr Neuropharmacol. 2009;7:65-74. doi: 10.2174/157015909787602823. PubMed PMID: 19721819; PubMed Central PMCID: PMCPMC2724665.
  2. Richer S, Stiles W, Zargar P, Rezaei M, Vo T, Bone R, et al. The human lens: A living biometric indicator of health status and successful aging. Studies on the Cornea and Lens. 2015:155-86. doi: 10.1007/978-1-4939-1935-2_10.
  3. Carocho M, Ferreira IC. A review on antioxidants, prooxidants and related controversy: natural and synthetic compounds, screening and analysis methodologies and future perspectives. Food Chem Toxicol. 2013;51:15-25. doi: 10.1016/j.fct.2012.09.021. PubMed PMID: 23017782.
  4. Chung CH, Jung W, Keum H, Kim TW, Jon S. Nanoparticles Derived from the Natural Antioxidant Rosmarinic Acid Ameliorate Acute Inflammatory Bowel Disease. ACS Nano. 2020;14:6887-96. doi: 10.1021/acsnano.0c01018. PubMed PMID: 32449857.
  5. Naziroglu M, Celik O, Ozgul C, Cig B, Dogan S, Bal R, et al. Melatonin modulates wireless (2.45 GHz)-induced oxidative injury through TRPM2 and voltage gated Ca(2+) channels in brain and dorsal root ganglion in rat. Physiol Behav. 2012;105:683-92. doi: 10.1016/j.physbeh.2011.10.005. PubMed PMID: 22019785.
  6. Mushtaq N, Schmatz R, Pereira LB, Ahmad M, Stefanello N, Vieira JM, et al. Rosmarinic acid prevents lipid peroxidation and increase in acetylcholinesterase activity in brain of streptozotocin-induced diabetic rats. Cell Biochem Funct. 2014;32:287-93. doi: 10.1002/cbf.3014. PubMed PMID: 24301255.
  7. Haybar H, Goudarzi M, Mehrzadi S, Aminzadeh A, Khodayar MJ, Kalantar M, et al. Effect of gemfibrozil on cardiotoxicity induced by doxorubicin in male experimental rats. Biomed Pharmacother. 2019;109:530-5. doi: 10.1016/j.biopha.2018.10.101. PubMed PMID: 30551518.
  8. Mehrabani M, Goudarzi M, Mehrzadi S, Siahpoosh A, Mohammadi M, Khalili H, et al. Crocin: a protective natural antioxidant against pulmonary fibrosis induced by bleomycin. Pharmacol Rep. 2020;72:992-1001. doi: 10.1007/s43440-019-00023-y. PubMed PMID: 31997260.
  9. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976;72:248-54. doi: 10.1006/abio.1976.9999. PubMed PMID: 942051.
  10. Nesari A, Mansouri MT, Khodayar MJ, Rezaei M. Preadministration of high-dose alpha-tocopherol improved memory impairment and mitochondrial dysfunction induced by proteasome inhibition in rat hippocampus. Nutr Neurosci. 2021;24:119-29. doi: 10.1080/1028415X.2019.1601888. PubMed PMID: 31084475.
  11. Goudarzi M, Kalantar M, Kalantar H. The hepatoprotective effect of gallic acid on mercuric chloride-induced liver damage in rats. Jundishapur Journal of Natural Pharmaceutical Products. 2017;12. doi: 10.5812/jjnpp.12345.
  12. Mehrzadi S, Mehrabani M, Malayeri AR, Bakhshayesh M, Kalantari H, Goudarzi M. Ellagic acid as a potential antioxidant, alleviates methotrexate-induced hepatotoxicity in male rats. Acta Chir Belg. 2019;119:69-77. doi: 10.1080/00015458.2018.1455419. PubMed PMID: 29587597.
  13. Goudarzi M, Amiri S, Nesari A, Hosseinzadeh A, Mansouri E, Mehrzadi S. The possible neuroprotective effect of ellagic acid on sodium arsenate-induced neurotoxicity in rats. Life Sci. 2018;198:38-45. doi: 10.1016/j.lfs.2018.02.022. PubMed PMID: 29455002.
  14. Shahin S, Singh VP, Shukla RK, Dhawan A, Gangwar RK, Singh SP, et al. 2.45 GHz microwave irradiation-induced oxidative stress affects implantation or pregnancy in mice, Mus musculus. Appl Biochem Biotechnol. 2013;169:1727-51. doi: 10.1007/s12010-012-0079-9. PubMed PMID: 23334843.
  15. Salah MB, Abdelmelek H, Abderraba M. Effects of olive leave extract on metabolic disorders and oxidative stress induced by 2.45 GHz WIFI signals. Environ Toxicol Pharmacol. 2013;36:826-34. doi: 10.1016/j.etap.2013.07.013. PubMed PMID: 23994945.
  16. Ozguner F, Armagan A, Koyu A, Caliskan S, Koylu H. A novel antioxidant agent caffeic acid phenethyl ester prevents shock wave-induced renal tubular oxidative stress. Urol Res. 2005;33:239-43. doi: 10.1007/s00240-005-0470-x. PubMed PMID: 15877224.
  17. Oksay T, Naziroglu M, Dogan S, Guzel A, Gumral N, Kosar PA. Protective effects of melatonin against oxidative injury in rat testis induced by wireless (2.45 GHz) devices. Andrologia. 2014;46:65-72. doi: 10.1111/and.12044. PubMed PMID: 23145464.
  18. Amara S, Abdelmelek H, Garrel C, Guiraud P, Douki T, Ravanat JL, et al. Effects of subchronic exposure to static magnetic field on testicular function in rats. Arch Med Res. 2006;37:947-52. doi: 10.1016/j.arcmed.2006.06.004. PubMed PMID: 17045109.
  19. Zhang Y, Chen X, Yang L, Zu Y, Lu Q. Effects of rosmarinic acid on liver and kidney antioxidant enzymes, lipid peroxidation and tissue ultrastructure in aging mice. Food Funct. 2015;6:927-31. doi: 10.1039/c4fo01051e. PubMed PMID: 25635678.
  20. Fernando PM, Piao MJ, Kang KA, Ryu YS, Hewage SR, Chae SW, et al. Rosmarinic Acid Attenuates Cell Damage against UVB Radiation-Induced Oxidative Stress via Enhancing Antioxidant Effects in Human HaCaT Cells. Biomol Ther (Seoul). 2016;24:75-84. doi: 10.4062/biomolther.2015.069. PubMed PMID: 26759705; PubMed Central PMCID: PMCPMC4703356.
  21. Yurekli AI, Ozkan M, Kalkan T, Saybasili H, Tuncel H, Atukeren P, et al. GSM base station electromagnetic radiation and oxidative stress in rats. Electromagn Biol Med. 2006;25:177-88. doi: 10.1080/15368370600875042. PubMed PMID: 16954120.
  22. Park JA, Kim S, Lee SY, Kim CS, Kim DK, Kim SJ, et al. Beneficial effects of carnosic acid on dieldrin-induced dopaminergic neuronal cell death. Neuroreport. 2008;19:1301-4. doi: 10.1097/WNR.0b013e32830abc1f. PubMed PMID: 18695511.
  23. Hajhosseini L, Khaki A, Merat E, Ainehchi N. Effect of rosmarinic acid on sertoli cells apoptosis and serum antioxidant levels in rats after exposure to electromagnetic fields. Afr J Tradit Complement Altern Med. 2013;10:477-80. doi: 10.4314/ajtcam.v10i6.14. PubMed PMID: 24311872; PubMed Central PMCID: PMCPMC3847387.
  24. Aitken RJ, Roman SD. Antioxidant systems and oxidative stress in the testes. Adv Exp Med Biol. 2008;636:154-71. doi: 10.1007/978-0-387-09597-4_9. PubMed PMID: 19856167.
  25. Pahune PP, Choudhari AR, Muley PA. The total antioxidant power of semen and its correlation with the fertility potential of human male subjects. J Clin Diagn Res. 2013;7:991-5. doi: 10.7860/JCDR/2013/4974.3040. PubMed PMID: 23905087; PubMed Central PMCID: PMCPMC3708257.
  26. Samarth RM, Samarth M. Protection against radiation-induced testicular damage in Swiss albino mice by Mentha piperita (Linn.). Basic Clin Pharmacol Toxicol. 2009;104:329-34. doi: 10.1111/j.1742-7843.2009.00384.x. PubMed PMID: 19320637.
  27. Kesari KK, Behari J. Effects of microwave at 2.45 GHz radiations on reproductive system of male rats. Toxicological and Environ Chemistry. 2010;92:1135-47. doi: 10.1080/02772240903233637.
  28. Saygin M, Caliskan S, Karahan N, Koyu A, Gumral N, Uguz A. Testicular apoptosis and histopathological changes induced by a 2.45 GHz electromagnetic field. Toxicol Ind Health. 2011;27:455-63. doi: 10.1177/0748233710389851. PubMed PMID: 21310776.
  29. Salama N, Kishimoto T, Kanayama HO. Effects of exposure to a mobile phone on testicular function and structure in adult rabbit. Int J Androl. 2010;33:88-94. doi: 10.1111/j.1365-2605.2008.00940.x. PubMed PMID: 19076254.
  30. Khaki A, Imani S, Golzar FS. Effects of rosmarinic acid on male sex hormones (testosterone-FSH-LH) and testis tissue apoptosis after exposure to electromagnetic field (EMF) in rats. African Journal of Pharmacy and Pharmacology. 2012;6:248-52. doi: 10.5897/AJPP11.701.
  31. Raisi A, Davoodi F, Mohammadi R. Protective effects of rosmarinic acid on testicular torsion-detorsion in an animal model. Iranian Journal of Veterinary Surgery. 2022;17:80-6.
  32. Alagawany M, Abd El-Hack ME, Farag MR, Gopi M, Karthik K, Malik YS, et al. Rosmarinic acid: modes of action, medicinal values and health benefits. Anim Health Res Rev. 2017;18:167-76. doi: 10.1017/S1466252317000081. PubMed PMID: 29110743.
  33. Soobrattee MA, Neergheen VS, Luximon-Ramma A, Aruoma OI, Bahorun T. Phenolics as potential antioxidant therapeutic agents: mechanism and actions. Mutat Res. 2005;579:200-13. doi: 10.1016/j.mrfmmm.2005.03.023. PubMed PMID: 16126236.
  34. Del Bano MJ, Castillo J, Benavente-Garcia O, Lorente J, Martin-Gil R, Acevedo C, et al. Radioprotective-antimutagenic effects of rosemary phenolics against chromosomal damage induced in human lymphocytes by gamma-rays. J Agric Food Chem. 2006;54:2064-8. doi: 10.1021/jf0581574. PubMed PMID: 16536576.
  35. Renzulli C, Galvano F, Pierdomenico L, Speroni E, Guerra MC. Effects of rosmarinic acid against aflatoxin B1 and ochratoxin-A-induced cell damage in a human hepatoma cell line (Hep G2). J Appl Toxicol. 2004;24:289-96. doi: 10.1002/jat.982. PubMed PMID: 15300717.
  36. Attah TA, Ayantunji B, Adamu A, Omede A, Leleji J, Hussiani S, et al. Biological Effects of High Radiofrequency Radiation on Wistar Rats: A Literature Review. Journal of Public Health International. 2022;5:1-31. doi: 10.14302/issn.2641-4538.jphi-22-4197.
  37. Nadeem M, Imran M, Aslam Gondal T, Imran A, Shahbaz M, Muhammad Amir R, et al. Therapeutic potential of rosmarinic acid: A comprehensive review. Applied Sciences. 2019;9:3139. doi: 10.3390/app9153139.