Volume 18, Issue 8 (August 2020)                   IJRM 2020, 18(8): 667-682 | Back to browse issues page


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Mehdikhani H, Shariati M, Forouzanfar M, Hosseini S E. Protective effects of Ceratonia siliqua extract on protamine gene expression, testicular function and testicular histology in doxorubicin-treated adult rats. IJRM 2020; 18 (8) :667-682
URL: http://ijrm.ir/article-1-1650-en.html
1- Department of Biology, Shiraz Branch, Islamic Azad University, Shiraz, Iran
2- Department of Biology, Kazerun Branch, Islamic Azad University, Kazerun, Iran. , mehrdadshariati@hotmail.com
3- Department of Biology, Marvdasht Branch, Islamic Azad University, Marvdasht, Iran.
4- Department of Biology, Shiraz Branch, Islamic Azad University, Shiraz, Iran.
Abstract:   (1956 Views)
Abstract
Background:  Spermatogenesis is a complex process under the influence of many different genes.
Objective: This study was to investigate the possible effects of Ceratonia siliqua hydroalcoholic extract (CSHAE) on protamine gene expression, testicular function and testicular histology in doxorubicin-treated rats.   
Materials and Methods: 56 adult male rats (210± 10 g) were divided into 7 groups (n=8/each). The control group left untreated; the sham group  received 0.3ml distilled water intraperitoneally; The negative control group  received 3 mg/kg doxorubicin, intraperitoneally, once a week for 28 days; the positive control group received 600 mg/kg of  CSHAE, orally, for 48 days; the experimental groups 1, 2 and 3 received 150, 300 and 600 mg/kg of  CSHAE,  orally, respectively for 48 days, as well as 3 mg/kg doxorubicin once a week for 28 days. Hematoxylin-eosin staining was used in histological study of testes, and enzyme-linked immunosorbent assay method was used in measuring serum levels of testosterone. Protamine gene expression was determined by Real Time PCR method.
Results: Mean body weight (p=0.009), testicular weight (p<0.001), testicular volume (p<0.001), testosterone level (p=0.022), the count of Leydig (p=0.014), spermatogonia (p =0.046), spermatocyte (p =0.025), and spermatid (p=0.006) cells, as well as protamine gene expression (p=0.008) were significantly increased in experimental group 2 compared to the negative control group. The testicular tissue regeneration was observed in the experimental group 2.
Conclusion: CSHAE has protective effect on doxorubicin-induced testicular injuries.
 
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Type of Study: Original Article | Subject: Reproductive Andrology

References
1. Shalet SM. Normal testicular function and spermatogenesis. Pediat Blood Cancer 2009; 53: 285-288. [DOI:10.1002/pbc.22000] [PMID]
2. He Z, Kokkinaki M, Pant D, Gallicano GI, Dym M. Small RNA molecules in the regulation of spermatogenesis. Reproduction 2009; 137: 901-911. [DOI:10.1530/REP-08-0494] [PMID]
3. Ramaswamy S, Weinbauer GF. Endocrine control of spermatogenesis: Role of FSH and LH/testosterone. Spermatogenesis 2015; 4: e996025-1- e996025-15. [DOI:10.1080/21565562.2014.996025] [PMID] [PMCID]
4. Schulte RT, Ohl DA, Sigman M, Smith GD. Sperm DNA damage in male infertility: etiologies, assays, and outcomes. J Assist Reprod Genet 2010; 27: 3-12. [DOI:10.1007/s10815-009-9359-x] [PMID] [PMCID]
5. O'Flynn O'Brien KL, Varghese AC, Agarwal A. The genetic causes of male factor infertility: A review. Fertil Steril 2010; 93: 1-12. [DOI:10.1016/j.fertnstert.2009.10.045] [PMID]
6. Imken L, Rouba H, El Houate B, Louanjli N, Barakat A, Chafik A, et al. Mutations in the protamine locus: association with spermatogenic failure? Mol Hum Reprod 2009; 15: 733-738. [DOI:10.1093/molehr/gap056] [PMID]
7. Lüke L, Vicens A, Tourmente M, Roldan ERS. Evolution of protamine genes and changes in sperm head phenotype in rodents. Biol Reprod 2014; 90: 67-74. [DOI:10.1095/biolreprod.113.115956] [PMID]
8. Ravel C, Chantot-Bastaraud S, El Houate B, Berthaut I, Verstraete L, De Larouziere V, et al. Mutations in the protamine 1 gene associated with male infertility. Mol Hum Reprod 2007; 13: 461-464. [DOI:10.1093/molehr/gam031] [PMID]
9. Jodar M, Oliva R. Protamine alterations in human spermatozoa. Adv Exp Med Biol 2014; 791: 83-102. [DOI:10.1007/978-1-4614-7783-9_6] [PMID]
10. Donkin I, Barrès R. Sperm epigenetics and influence of environmental factors. Mol Metab 2018; 14: 1-11. [DOI:10.1016/j.molmet.2018.02.006] [PMID] [PMCID]
11. Taskin E, Dursun N. Recovery of adriamycin induced mitochondrial dysfunction in liver by selenium. Cytotechnology 2015; 67: 977-986. [DOI:10.1007/s10616-014-9736-x] [PMID] [PMCID]
12. Zanetti SR, Maldonado EN, Aveldano MI. Doxorubicin affects testicular lipids with long-chain (C18-C22) and very long-chain (C24-C32) polyunsaturated fatty acids. Cancer Res 2007; 67: 6973-6980. [DOI:10.1158/0008-5472.CAN-07-0376] [PMID]
13. Brilhante O, Okada FK, Sasso-Cerri E, Stumpp T, Miraglia SM. Late morfofunctional alterations of the Sertoli cell caused by doxorubicin administered to prepubertal rats. Reprod Biol Endocrinol 2012; 10: 79-94. [DOI:10.1186/1477-7827-10-79] [PMID] [PMCID]
14. Ekinci K, Yılmaz D, Ertekin C. Effects of moisture content and compression positions on mechanical properties of carob pod (Ceratonia siliqua L.). Afr J Agric Res 2010; 5: 1015-1021.
15. Bureš P, Pavlíček T, Horová L, Nevo E. Microgeographic genome size differentiation of the carob tree, Ceratonia siliqua, at 'Evolution Canyon', Israel. Ann Bot 2004; 93: 529-535. [DOI:10.1093/aob/mch074] [PMID] [PMCID]
16. Durazzo A, Turfani V, Narducci V, Azzini E, Maiani G, Carcea M. Nutritional characterisation and bioactive components of commercial carobs flours. Food Chem 2014; 153: 109-113. [DOI:10.1016/j.foodchem.2013.12.045] [PMID]
17. Goulas V, Stylos E, Chatziathanasiadou MV, Mavromoustakos T, Tzakos AG. Functional components of carob fruit: Linking the chemical and biological space. Int J Mol Sci 2016; 17: 1875-1894. [DOI:10.3390/ijms17111875] [PMID] [PMCID]
18. Eldahshan OA. Isolation and structure elucidation of phenolic compounds of carob leaves grown in Egypt. Curr Res J Biol Sci 2011; 3: 52-55.
19. Azab A. Carob (Ceratonia siliqua): Health, medicine and chemistry. Eur Chem Bull 2017; 6: 456-469. [DOI:10.17628/ecb.2017.6.456-469]
20. Dakia PA, Wathelet B, Paquot M. Isolation and chemical evaluation of carob (Ceratonia siliqua L.) seed germ. Food Chemistry 2007; 102: 1368-1374. [DOI:10.1016/j.foodchem.2006.05.059]
21. Ayaz FA, Torun H, Ayaz S, Correia PJ, Alaiz M, Sanz C, et al. Determination of chemical composition of anatolian carob pod (Ceratonia siliqua L.): sugars, amino and organic acids, minerals and phenolic compounds. Journal of Food Quality 2007; 30: 1040-1055. [DOI:10.1111/j.1745-4557.2007.00176.x]
22. Macho-González A, Garcimartín A, Naes F, López-Oliva ME, Amores-Arrojo A, González-Muñoz MJ, et al. Effects of fiber purified extract of carob fruit on fat digestion and postprandial lipemia in healthy rats. J Agric Food Chem 2018; 66: 6734-6741. [DOI:10.1021/acs.jafc.8b01476] [PMID]
23. Zhu BJ, Zayed MZ, Zhu HX, Zhao J, Li SP. Functional polysaccharides of carob fruit: a review. Chin Med 2019; 14: 40-49. [DOI:10.1186/s13020-019-0261-x] [PMID] [PMCID]
24. El-Haskoury R, Al-Waili N, El-Hilaly J, Al-Waili W, Lyoussi B. Antioxidant, hypoglycemic, and hepatoprotective effect of aqueous and ethyl acetate extract of carob honey in streptozotocin-induced diabetic rats. Vet World 2019; 12: 1916-1923. [DOI:10.14202/vetworld.2019.1916-1923] [PMID] [PMCID]
25. Rtibi K, Selmi S, Jabri MA, El-Benna J, Amri M, Marzouki L, et al. Protective effect of Ceratonia siliqua L. against a dextran sulfate sodium-induced alterations in liver and kidney in rat. J Med Food 2016; 19: 882-889. [DOI:10.1089/jmf.2016.0020] [PMID]
26. Corsi L, Avallone R, Cosenza F, Farina F, Baraldi C, Baraldi M. Antiproliferative effects of Ceratonia siliqua L. on mouse hepatocellular carcinoma cell line. Fitoterapia 2002; 73: 674-684. [DOI:10.1016/S0367-326X(02)00227-7]
27. Sassi A, Bouhlel I, Mustapha N, Mokdad-Bzeouich I, Chaabane F, Ghedira K, et al. Assessment in vitro of the genotoxicity, antigenotoxicity and antioxidant of Ceratonia siliqua L. extracts in murine leukaemia cells L1210 by comet assay. Regul Toxicol Pharmacol 2016; 77: 117-124. [DOI:10.1016/j.yrtph.2016.02.009] [PMID]
28. Ata A, Yildiz-Gulay O, Güngör S, Balic A, Gulay MS. The effect of carob (Ceratonia siliqua) bean extract on male New Zealand White rabbit semen. World Rabbit Sci 2018; 26: 209-215. [DOI:10.4995/wrs.2018.10154]
29. Mahdiani E, Khadem Haghighian H, Javadi M, Karami AA, Kavianpour M. Effect of Carob (Ceratonia siliqua L.) oral supplementation on changes of semen parameters, oxidative stress, inflammatory biomarkers and reproductive hormones in infertile men. Sci J Kurdistan Univ Med Sci 2018; 23: 56-66.
30. Jain H, Parial SD, Jarald E, Daud AS, Ahmad S. Extraction of Ashwagandha by conventional extraction methods and evaluation of its anti-stress activity. International Journal of Green Pharmacy (IJGP) 2010; 4: 183-185. [DOI:10.4103/0973-8258.69178]
31. Mokhtari M, Sharifi E, Azadian Sh. The effects of hydro alcoholic extract of Ceratonia siliqua L. seeds on pituitary--testis hormones and spermatogenesis in rat. Advances in Environmental Biology 2012; 2778-2784.
32. Bazrafkan M, Sobhani A. Study of spermatogenesis in wistar adult rats administrated to long term of ruta graveolens. Jentashapir Journal of Health Research 2014; 5: e21870. [DOI:10.17795/jjhr-21870]
33. Boussada M, Ali RB, Said AB, Bokri K, Akacha AB, Dziri C, et al. Selenium and a newly synthesized Thiocyanoacetamide reduce Doxorubicin gonadotoxicity in male rat. Biomed Pharmacother 2017; 89: 1005-1017. [DOI:10.1016/j.biopha.2017.03.002] [PMID]
34. Badkoobeh P, Parivar K, Kalantar SM, Hosseini SD, Salabat A. Protective effect of nano-zinc oxide on histological parameters of testis following doxorubicin treatment. Journal of Cell & Tissue 2013; 4: 159-167.
35. Faraji Z, Nikzad H, Parivar K, Nikzad M. The effect of aqueous extract of Salep Tubers on the structure of testis and sexual hormones in male mice. J Jahrom Univ Med Sci 2013; 11: 61-66. [DOI:10.29252/jmj.11.1.10]
36. Bustin SA. Real-time reverse transcription PCR. Encyclopedia of diagnostic genomics and proteomics 2005; 1131-1135. [DOI:10.3109/9780203997352.226]
37. Popal W, Nagy ZP. Laboratory processing and intracytoplasmic sperm injection using epididymal and testicular spermatozoa: what can be done to improve outcomes? Clinics 2013; 68: 125-130. [DOI:10.6061/clinics/2013(Sup01)14]
38. Lim NYN, Roco CA, Frostegård Å. Transparent DNA/RNA co-extraction workflow protocol suitable for inhibitor-rich environmental samples that focuses on complete DNA removal for transcriptomic analyses. Front Microbiol 2016; 7: 1588-1602. [DOI:10.3389/fmicb.2016.01588] [PMID] [PMCID]
39. Mo Y, Wan R, Zhang Q. Application of reverse transcription-PCR and real-time PCR in nanotoxicity research. Methods Mol Biol 2012; 926: 99-112. [DOI:10.1007/978-1-62703-002-1_7] [PMID] [PMCID]
40. Singh J, Birbian N, Sinha S, Goswami A. A critical review on PCR, its types and applications. Int J Adv Res Biol Sci 2014; 1: 65-80.
41. Vendramini V, Sasso-Cerri E, Miraglia SM. Amifostine reduces the seminiferous epithelium damage in doxorubicin-treated prepubertal rats without improving the fertility status. Reprod Biol Endocrinol 2010; 8: 3-15. [DOI:10.1186/1477-7827-8-3] [PMID] [PMCID]
42. Silva RC, Coelho Britto DM, de Fátima Pereira W, Brito-Melo GEA, Machado CT, Pedreira MM. Effect of short-and medium-term toxicity of doxorubicin on spermatogenesis in adult Wistar rats. Reprod Biol 2018; 18: 169-176. [DOI:10.1016/j.repbio.2018.03.002] [PMID]
43. Stumpp T, Freymüller E, Miraglia SM. Sertoli cell function in albino rats treated with etoposide during prepubertal phase. Histochem Cell Biol 2006; 126: 353-361. [DOI:10.1007/s00418-006-0168-3] [PMID]
44. Yeh YC, Lai HC, Ting CT, Lee WL, Wang LC, Wang KY, et al. Protection by doxycycline against doxorubicin-induced oxidative stress and apoptosis in mouse testes. Biochem Pharmacol 2007; 74: 969-980. [DOI:10.1016/j.bcp.2007.06.031] [PMID]
45. Uyeturk U, Uyeturk U, Firat T, Cetinkaya A, Tekce BK, Cakir S. Protective effects of rosmarinic acid on doxorubicin-induced testicular damage. Chemotherapy 2014; 60: 7-12. [DOI:10.1159/000365727] [PMID]
46. Cabral REL, Okada FK, Stumpp T, Vendramini V, Miraglia SM. Carnitine partially protects the rat testis against the late damage produced by doxorubicin administered during pre‐puberty. Andrology 2014; 2: 931-942. [DOI:10.1111/andr.279] [PMID]
47. Lachkar N, Al-Sobarry M, El Hajaji H, Lamkinsi T, Lachkar M, Cherrah Y, et al. Anti-inflammatory and antioxidant effect of Ceratonia siliqua L. methanol barks extract. J Chem Pharm Res 2016; 8: 202-210.
48. Soleimanzadeh A, Kian M, Moradi S, Mahmoudi S. Carob (Ceratonia siliqua L.) fruit hydro-alcoholic extract alleviates reproductive toxicity of lead in male mice: Evidence on sperm parameters, sex hormones, oxidative stress biomarkers and expression of Nrf2 and iNOS. Avicenna J Phytomed 2019; 10: 35-49.
49. Vafaei A, Mohammadi S, Fazel A, Soukhtanloo M, Mohammadipour A, Beheshti F. Effects of carob (Ceratonia siliqua) on sperm quality, testicular structure, testosterone level and oxidative stress in busulfan-induced infertile mice. Pharm Sci 2018; 24: 104-111. [DOI:10.15171/PS.2018.16]
50. Bengoechea C, Puppo MC, Romero A, Cordobes F, Guerrero A. Linear and non-linear viscoelasticity of emulsions containing carob protein as emulsifier. Journal of Food Engineering 2008; 87: 124-135. [DOI:10.1016/j.jfoodeng.2007.11.024]
51. Hossein MS, Tareq KMA, Hammano KI, Tsujii H. Effect of fatty acids on boar sperm motility, viability and acrosome reaction. Reprod Med Biol 2007; 6: 235-239. [DOI:10.1111/j.1447-0578.2007.00191.x] [PMID] [PMCID]
52. Melmed S, Polonsky KS, Larsen PR, Kronenberg HM. Chapter 38: Gastrointestinal hormones and gut endocrine tumors. Williams text book of endocrinology. 13th ed. Philadelphia: Elsevier 2016: 1701-1722.
53. Verma R, Samanta R, Krishna A. Comparative effects of estrogen and phytoestrogen, genistein on testicular activities of streptozotocin-induced type 2 diabetic mice. Reprod Sci 2019; 26: 1294-1306. [DOI:10.1177/1933719118815576] [PMID]
54. Jalili C, Ahmadi S, Roshankhah S, Salahshoor MR. Effect of genistein on reproductive parameter and serum nitric oxide levels in morphine-treated mice. Int J Reprod Biomed 2016; 14: 95-102. [DOI:10.29252/ijrm.14.2.95]
55. Al-Maghrebi M, Renno WM. Genistein alleviates testicular ischemia and reperfusion injury-induced spermatogenic damage and oxidative stress by suppressing abnormal testicular matrix metalloproteinase system via the Notch 2/Jagged 1/Hes-1 and caspase-8 pathways. J Physiol Pharmacol 2016; 67: 129-137.
56. Chi H, Chun K, Son H, Kim J, Kim G, Roh S. Effect of genistein administration on the recovery of spermatogenesis in the busulfan-treated rat testis. Clin Exp Reprod Med 2013; 40: 60-66. [DOI:10.5653/cerm.2013.40.2.60] [PMID] [PMCID]
57. Kim JS, Heo K, Yi JM, Gong EJ, Yang K, Moon C, et al. Genistein mitigates radiation‐induced testicular injury. Phytother Res 2012; 26: 1119-1125. [DOI:10.1002/ptr.3689] [PMID]
58. Mehraban Z, Ghaffari Novin M, Golmohammadi MG, Sagha M, Ziai SA, Abdollahifar MA, et al. Protective effect of gallic acid on testicular tissue, sperm parameters, and DNA fragmentation against toxicity induced by cyclophosphamide in Adult NMRI mice. Urol J 2020; 17: 78-85.
59. Mehraban Z, Ghaffari Novin M, Golmohammadi MG, Sagha M, Pouriran K, Nazarian H. Protective effect of gallic acid on apoptosis of sperm and in vitro fertilization in adult male mice treated with cyclophosphamide. J Cell Biochem 2019; 120: 17250-17257. [DOI:10.1002/jcb.28987] [PMID]
60. Ma B, Zhang J, Zhu Z, Zhao A, Zhou Y, Ying H, et al. Luteolin ameliorates testis injury and blood-testis barrier disruption through the Nrf2 signaling pathway and by upregulating Cx43. Mol Nutr Food Res 2019; 63: e1800843. [DOI:10.1002/mnfr.201800843] [PMID]
61. Khorsandi L, Orazizadeh M, Moradi-Gharibvand N, Hemadi M, Mansouri E. Beneficial effects of quercetin on titanium dioxide nanoparticles induced spermatogenesis defects in mice. Environ Sci Pollut Res 2017; 24: 5595-5606. [DOI:10.1007/s11356-016-8325-2] [PMID]
62. Baltaci BB, Uygur R, Caglar V, Aktas C, Aydin M, Ozen OA. Protective effects of quercetin against arsenic‐induced testicular damage in rats. Andrologia 2016; 48: 1202-1213. [DOI:10.1111/and.12561] [PMID]
63. Abd-Ellah MF, Aly HA, Mokhlis HA, Abdel-Aziz AH. Quercetin attenuates di-(2-ethylhexyl) phthalate-induced testicular toxicity in adult rats. Hum Exp Toxicol 2016; 35: 232-243. [DOI:10.1177/0960327115580602] [PMID]
64. Ben Abdallah F, Fetoui H, Zribi N, Fakhfakh F, Keskes L. Quercetin attenuates lambda cyhalothrin‐induced reproductive toxicity in male rats. Environ Toxicol 2013; 28: 673-680. [DOI:10.1002/tox.20762] [PMID]
65. Jahan S, Ain QU, Ullah H. Therapeutic effects of quercetin against bisphenol A induced testicular damage in male Sprague Dawley rats. Syst Biol Reprod Med 2016; 62: 114-124. [DOI:10.3109/19396368.2015.1115139] [PMID]
66. Custódio L, Fernandes E, Escapa AL, López-Avilés S, Fajardo A, Aligué R et al. Antioxidant activity and in vitro inhibition of tumor cell growth by leaf extracts from the carob tree (Ceratonia siliqua). Pharmaceutical Biology 2009; 47: 721-728. [DOI:10.1080/13880200902936891]
67. Sadeghnia HR, Kamkar M, Assadpour E, Boroushaki MT, Ghorbani A. Protective effect of safranal, a constituent of Crocus sativus, on quinolinic acid-induced oxidative damage in rat hippocampus. Iran J Basic Med Sci 2013; 16: 73-82.

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