Advertisement

Journal of Bioenergetics and Biomembranes

, Volume 51, Issue 5, pp 371–379 | Cite as

Protection from ionizing radiation-induced genotoxicity and apoptosis in rat bone marrow cells by HESA-A: a new herbal-marine compound

  • Maryam Hazbavi
  • Mansoureh Zarei
  • Roghayeh Nazaralivand
  • Hojattollah Shahbazian
  • Mohsen ChekiEmail author
Article
  • 37 Downloads

Abstract

HESA-A is an herbal-marine compound which improves the quality of life of end-stage cancer patients. The aim of the present study was to evaluate the possible protective effect of HESA-A against IR-induced genotoxicity and apoptosis in rat bone marrow. Rats were given HESA-A orally at doses of 150 and 300 mg/kg body weight for seven consecutive days. On the seventh day, the rats were irradiated with 4 Gy X-rays at 1 h after the last oral administration. The micronucleus assay, reactive oxygen species (ROS) level analysis, hematological analysis and flow cytometry were used to assess radiation antagonistic potential of HESA-A. Administration of 150 and 300 mg/kg of HESA-A to irradiated rats significantly reduced the frequencies of micronucleated polychromatic erythrocytes (MnPCEs) and micronucleated normochromatic erythrocytes (MnNCEs), and also increased PCE/(PCE + NCE) ratio in bone marrow cells. Moreover, pretreatment of irradiated rats with HESA-A (150 and 300 mg/kg) significantly decreased ROS level and apoptosis in bone marrow cells, and also increased white blood cells count in peripheral blood. For the first time in this study, it was observed that HESA-A can have protective effects against radiation-induced genotoxicity and apoptosis in bone marrow cells. Therefore, HESA-A can be considered as a candidate for future studies to reduce the side effects induced by radiotherapy in cancer patients.

Keywords

Ionizing radiation Bone marrow cells Radioprotector HESA-A Genotoxicity 

Notes

Funding

This study was funded by grants (U-97001) from the vice chancellor of research at Ahvaz Jundishapur University of Medical Sciences (Iran).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All experiments on rats were carried out based of the NIH Guide for Care and Use of Laboratory Animals. All study protocols were approved in Animal Ethical Committee of Ahvaz Jundishapur University of Medical Sciences (IR.AJUMS.REC.1396.699).

References

  1. Abbasi MM, Helli S, Monfaredan A, Jahanban-Esfahlan R (2015) Hesa-A improves clinical outcome of oral carcinoma by affecting p53 gene expression in vivo. Asian Pac J Cancer Prev 16:4169–4172PubMedGoogle Scholar
  2. Abou-Seif MA, El-Naggar MM, El-Far M, Ramadan M, Salah N (2003) Prevention of biochemical changes in gamma-irradiated rats by some metal complexes. Clin Chem Lab Med 41:926–933PubMedGoogle Scholar
  3. Ahmadi A, Mohagheghi MA, Fazeli MS, Nahavandian B, Bashardoost N, Jarahi AM, Gharipoor M (2005a) HESA-A: new treatment for breast cancer and choroidal metastasis. Med Sci Monit 11:300–303Google Scholar
  4. Ahmadi A, Naderi G, Asgary S (2005b) Evaluation of hepatoprotective potential of HESA-A (a marine compound) pretreatment against thioacetamide-induced hepatic damage in rabbits. Drugs Exp Clin Res 31:1–6PubMedGoogle Scholar
  5. Ahmadi A, Mohagheghi M, Karimi M, Golestanha SA, Naseri M (2009) Anticancer effects of HESA-A in patients with metastatic colon cancer. Integr Cancer Ther 8:71–74PubMedGoogle Scholar
  6. Ahmadi A, Mohagheghi M, Karimi M, Golestanha SA, Naseri M, Faghihzadeh S, Habibi G (2010) Therapeutic effects of HESA-A in patients with end-stage metastatic cancers. Integr Cancer Ther 9:32–35PubMedGoogle Scholar
  7. Ahmadian N, Pashaei-Asl R, Samadi N, Rahmati-Yamchi M, Rashidi MR, Ahmadian M, Joshaghani HR (2016) Hesa-a effects on cell cycle signaling in esophageal carcinoma cell line. Middle East J Dig Dis 8:297–302PubMedPubMedCentralGoogle Scholar
  8. Al-Hazzaa AA, El-Habit OHM, Al-Meer RS (2007) Evaluation of the protective role of vitamin B12 on gamma radiation induced cytotoxicity in mice. J King Saud Univ Science 19:97–107Google Scholar
  9. Alizadeh AM, Ahmadi A, Mohammadzadeh M, Paknejad M, Mohagheghi M (2009) The effect of HESA-A, an herbal-marine compound, on wound healing process: an experimental study. Res J Biol Sci 4:298–302Google Scholar
  10. Al-Meer RS, El-Habit OHM, Al-Hazaa AA (2011) Adaptive response to ionizing radiation and the role of vitamin B12 in amelioration radiation protection standards. J King Saud Univ Science 23:197–204Google Scholar
  11. Asadullina NR, Usacheva AM, Smirnova VS, Gudkov SV (2010) Antioxidative and radiation modulating properties of guanosine-5′-monophosphate. Nucleosides Nucleotides Nucleic Acids 29:786–799PubMedGoogle Scholar
  12. Bourre JM, Paquotte P (2008) Seafood (wild and farmed) for the elderly: contribution to the dietary intakes of iodine, selenium, DHA and vitamins B12 and D. J. Nutr. Health Aging 12:186–192PubMedGoogle Scholar
  13. Caruso F, Rossi M (2004) Antitumor titanium compounds. Mini Rev Med Chem 4:49–60PubMedGoogle Scholar
  14. Cheki M, Mihandoost E, Shirazi A, Mahmoudzadeh A (2016a) Prophylactic role of some plants and phytochemicals against radio-genotoxicity in human lymphocytes. J Cancer Res Ther 12:1234PubMedGoogle Scholar
  15. Cheki M, Shirazi A, Mahmoudzadeh A, Bazzaz JT, Hosseinimehr SJ (2016b) The radioprotective effect of metformin against cytotoxicity and genotoxicity induced by ionizing radiation in cultured human blood lymphocytes. Mutat Res Toxicol Environ Mutagen 809:24–32Google Scholar
  16. Cheki M, Yahyapour R, Farhood B, Rezaeyan A, Shabeeb D, Amini P, Najafi M (2018) COX-2 in radiotherapy; a potential target for radioprotection and radiosensitization. Curr Mol Pharmacol 11:173–183PubMedGoogle Scholar
  17. Crescenti EJ, Medina VA, Croci M, Sambuco LA, Prestifilippo JP, Elverdin JC, Bergoc RM, Rivera ES (2011) Radioprotection of sensitive rat tissues by oligoelements se, Zn, Mn plus Lachesis muta venom. J Radiat Res 52(5):557–567PubMedGoogle Scholar
  18. Duan Y, Zhang H, Xie B, Yan Y, Li J, Xu F, Qin Y (2010) Whole body radioprotective activity of an acetone-water extract from the seedpod of Nelumbo nucifera Gaertn. seedpod. Food Chem Toxicol 48:3374–3384PubMedGoogle Scholar
  19. El-Gendy AM, El-Feky F, Mahmoud NH, Elsebakhy GSA (2018) Evaluation of nutritional quality of green tiger prawn, penaeus semisulcatus from land fisheries (Alexandria) and market (India). Egypt J Hosp Med 70:924–934Google Scholar
  20. Fleenor CJ, Marusyk A, DeGregori J (2010) Ionizing radiation and hematopoietic malignancies: altering the adaptive landscape. Cell Cycle 9:3077–3083Google Scholar
  21. Green DE, Rubin CT (2014) Consequences of irradiation on bone and marrow phenotypes, and its relation to disruption of hematopoietic precursors. Bone 63:87–94PubMedGoogle Scholar
  22. Gudkov SV, Guryev EL, Gapeyev AB, Sharapov MG, Bunkin NF, Shkirin AV, Zabelina TS, Glinushkin AP, Sevost'yanov MA, Belosludtsev KN, Chernikov AV, Bruskov VI, Zvyagin AV (2019) Unmodified hydrated С60 fullerene molecules exhibit antioxidant properties, prevent damage to DNA and proteins induced by reactive oxygen species and protect mice against injuries caused by radiation-induced oxidative stress. Nanomedicine 15:37–46PubMedGoogle Scholar
  23. Guo J, Deng W, Zhang L, Li C, Wu P, Mao P (2007) Prediction of prostate cancer using hair trace element concentration and support vector machine method. Biol Trace Elem Res 116:257–272PubMedGoogle Scholar
  24. Hajhashemi V, Ghafghazi T, Balali M, Ahmadi A, Taher M, Rajabi P, Talebi A (2001) Toxicological studies on an anticancer drug (HESA-A) with marine origin. Med J Islam Acad Sci 14:145–149Google Scholar
  25. Halliwell B, Whiteman M (2004) Measuring reactive species and oxidative damage in vivo and in cell culture: how should you do it and what do the results mean? Br J Pharmacol 142:231–255PubMedPubMedCentralGoogle Scholar
  26. Hosseinimehr SJ (2015) The protective effects of trace elements against side effects induced by ionizing radiation. Radiat Oncol J 33:66–74PubMedPubMedCentralGoogle Scholar
  27. Jahanban-Esfahlan R, Abasi M, Sani HM, Abbasi MM, Akbarzadeh A (2015) Anti-proliferative effects of hesa-A on human cancer cells with different metastatic potential. Asian Pac J Cancer Prev 16:6963–6966PubMedGoogle Scholar
  28. Jia D, Koonce NA, Griffin RJ, Jackson C, Corry PM (2010) Prevention and mitigation of acute death of mice after abdominal irradiation by the antioxidant N-acetyl-cysteine (NAC). Radiat Res 173:579–589PubMedPubMedCentralGoogle Scholar
  29. Kolivand S, Motevaseli E, Cheki M, Mahmoudzadeh A, Shirazi A, Fait V (2017) The anti-apoptotic mechanism of metformin against apoptosis induced by ionizing radiation in human peripheral blood mononuclear cells. Klin Onkol 30:372–379PubMedGoogle Scholar
  30. Kumar A, Selvan TG, Tripathi AM, Choudhary S, Khan S, Adhikari JS, Chaudhury NK (2015) Sesamol attenuates genotoxicity in bone marrow cells of whole-body γ-irradiated mice. Mutagenesis 30:651–661PubMedGoogle Scholar
  31. Kumar A, Choudhary S, Adhikari JS, Chaudhury NK (2018) Sesamol ameliorates radiation induced DNA damage in hematopoietic system of whole body γ-irradiated mice. Environ Mol Mutagen 59:79–90PubMedGoogle Scholar
  32. Mantena SK, Unnikrishnan MK, Uma Devi P (2008) Radioprotective effect of sulfasalazine on mouse bone marrow chromosomes. Mutagenesis 23:285–292PubMedGoogle Scholar
  33. Mazur L, Augustynek A, Halicka HD, Deptała A (2003) Induction of apoptosis in bone marrow cells after treatment of mice with WR-2721 and gamma-rays: relationship to the cell cycle. Cell Biol Toxicol 19:13–27PubMedGoogle Scholar
  34. Mehdipour M, Zenouz AT, Abbasi MM, Mohajeri D, Damghani H, Helli S, Abdollahi B (2013) Evaluation of the effect of two systemic doses of HESA-A on prevention of induced tongue neoplasm in rats. J Dent Res Dent Clin Dent Prospects 7:218–224PubMedPubMedCentralGoogle Scholar
  35. Mehrbod P, Ideris A, Omar AR, Hair-Bejo M (2014) Prophylactic effect of herbal-marine compound (HESA-A) on influenza A virus infectivity. BMC Complement Altern Med 14:131PubMedPubMedCentralGoogle Scholar
  36. Moallem SA, Ahmadi A, Moshafi M, Taghavi MM (2011) Teratogenic effects of HESA-A, a natural anticancer product from Iran, in mice. Hum Exp Toxicol 30:851–859PubMedGoogle Scholar
  37. Mohseni M, Mihandoost E, Shirazi A, Sepehrizadeh Z, Bazzaz JT, Ghazi-khansari M (2012) Melatonin may play a role in modulation of bax and bcl-2 expression levels to protect rat peripheral blood lymphocytes from gamma irradiation-induced apoptosis. Mutat Res Mol Mech Mutagen 738:19–27Google Scholar
  38. Najafi M, Cheki M, Rezapoor S, Geraily G, Motevaseli E, Carnovale C, Shirazi A (2018) Metformin: prevention of genomic instability and cancer: a review. Mutat Res Toxicol Environ Mutagen 827:1–8Google Scholar
  39. Ormsby RJ, Lawrence MD, Blyth BJ, Bexis K, Bezak E, Murley JS, Sykes PJ (2014) Protection from radiation-induced apoptosis by the radioprotector amifostine (WR-2721) is radiation dose dependent. Cell Biol Toxicol 30:55–66PubMedGoogle Scholar
  40. Ran Y, Wang R, Lin F, Hasan M, Jia Q, Tang B, Li Q (2014) Radioprotective effects of Dragon’s blood and its extract against gamma irradiation in mouse bone marrow cells. Phys Medica 30:427–431Google Scholar
  41. Reagan-Shaw S, Nihal M, Ahmad N (2008) Dose translation from animal to human studies revisited. FASEB J 22:659–661Google Scholar
  42. Roudkenar MH, Bahmani P, Halabian R (2012) HESA-A exerts its cytoprotective effects through scavenging of free radicals: an in vitro study. Iran J Med Sci 37:47–53PubMedPubMedCentralGoogle Scholar
  43. Schmid W (1975) The micronucleus test. Mutat Res 31:9–15PubMedGoogle Scholar
  44. Shao L, Luo Y, Zhou D (2014) Hematopoietic stem cell injury induced by ionizing radiation. Antioxid Redox Signal 20:1447–1462PubMedPubMedCentralGoogle Scholar
  45. Sharapov MG, Novoselov VI, Fesenko EE, Bruskov VI, Gudkov SV (2017) The role of peroxiredoxin 6 in neutralization of X-ray mediated oxidative stress: effects on gene expression, preservation of radiosensitive tissues and postradiation survival of animals. Free Radic Res 51:148–166PubMedGoogle Scholar
  46. Sharapov MG, Novoselov VI, Penkov NV, Fesenko EE, Vedunova MV, Bruskov VI, Gudkov SV (2019) Protective and adaptogenic role of peroxiredoxin 2 (Prx2) in neutralization of oxidative stress induced by ionizing radiation. Free Radic Biol Med 134:76–86PubMedGoogle Scholar
  47. Singh A, Yashavarddhan MH, Kalita B, Ranjan R, Bajaj S, Prakash H, Gupta ML (2017) Podophyllotoxin and rutin modulates ionizing radiation-induced oxidative stress and apoptotic cell death in mice bone marrow and spleen. Front Immunol 8:183PubMedPubMedCentralGoogle Scholar
  48. Sood A, Chadha VD, Dhawan DK (2011) Radioprotective role of selenium after single-doseradioiodine (131I) exposure to red blood cells of rats. J Environ Pathol Toxicol Oncol 30:153–162PubMedGoogle Scholar
  49. Suman S, Maniar M, Fornace AJ, Datta K (2012) Administration of ON 01210. Na after exposure to ionizing radiation protects bone marrow cells by attenuating DNA damage response. Radiat Oncol 7:6PubMedPubMedCentralGoogle Scholar
  50. Syama Dayal J, Ponniah AJ, Imran Khan H, Madhu Babu EP, Ambasankar K, Kumarguru Vasagam KP (2013) Shrimps–a nutritional perspective. Curr Sci 104:1487–1491Google Scholar
  51. Targhi RG, Homayoun M, Mansouri S, Soukhtanloo M, Soleymanifard S, Seghatoleslam M (2017) Radio protective effect of black mulberry extract on radiation-induced damage in bone marrow cells and liver in the rat. Radiat Phys Chem 130:297–302Google Scholar
  52. Vahabpour R, Sadat SM, Zabihollahi R, Ahmadi A, Keivani H, Amini S, Aghasadeghi MR (2012) In vitro inhibitory effects of the herbal-marine compound HESA-A against replication of human immunodeficiency virus-1. Jundishapur J Microbiol 5:315Google Scholar
  53. Xue X, Han X, Li Y, Chu X, Miao W, Zhang J, Fan S (2017) Astaxanthin attenuates total body irradiation-induced hematopoietic system injury in mice via inhibition of oxidative stress and apoptosis. Stem Cell Res Ther 8:7PubMedPubMedCentralGoogle Scholar
  54. Zeng H, Combs GF Jr (2008) Selenium as an anticancer nutrient: roles in cell proliferation and tumor cell invasion. J Nutr Biochem 19:1–7PubMedGoogle Scholar
  55. Zhang YR, Wang JY, Li YY, Meng YY, Zhang Y, Yang FJ, Xu WQ (2019) Design and synthesis a mitochondria-targeted dihydronicotinamide as radioprotector. Free Radic Biol Med 136:45–51PubMedGoogle Scholar
  56. Zorov DB, Juhaszova M, Sollott SJ (2014) Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release. Physiol Rev 94:909–950PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Medical Physics, Faculty of MedicineAhvaz Jundishapur University of Medical SciencesAhvazIran
  2. 2.Department of Midwifery, Faculty of Nursing and MidwiferyAhvaz Jundishapur University of Medical SciencesAhvazIran
  3. 3.Department of Radiotherapy and Oncology, Golestan HospitalAhvaz Jundishapur University of Medical SciencesAhvazIran
  4. 4.Toxicology Research CenterAhvaz Jundishapur University of Medical SciencesAhvazIran

Personalised recommendations