Document Type : Original Article
Authors
1 Department of Medical Laboratory Sciences, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran
2 Department of Biology, Faculty of Science, Karaj Branch, Islamic Azad University, Alborz, Iran
3 Department of Biology, Faculty of Science, Central Tehran Branch, Islamic Azad University, Tehran, Iran
Abstract
Background: Hypericum perforatum is a flowering plant from the Hypericaceae family. This herb has warm and dry nature based on traditional medicine and includes many healing properties like noticeable effects on mild and moderate depression cases. Cyclophosphamide is used to treat various types of cancers and autoimmune diseases with the side effect of fertility reduction. We studied the effects of hydroalcoholic extract of Hypericum perforatum on the spermatogenesis process of cyclophosphamide-treated male mice.
Methods: In this experimental study, 70 adult BALB/c male mice weighing 26-28 g were randomly divided into 7 groups of 10, including, a control group (no injection), a sham group (normal saline), and three experimental groups which were treated with 5 mg/kg body weight of cyclophosphamide and also, doses of 50, 100, and 150 mg/kg body weight of hydroalcoholic extract, respectively. In addition, a cyclophosphamide group (5 mg/kg body weight) and an extract group (100 mg/kg body weight) were evaluated. All the injections were performed intraperitoneally for 10 consecutive days. After two weeks, blood samples were collected for a testosterone level examination. Testes and epididymis were removed for tissue sectioning and were stained with the H&E method. Data were analyzed using one-way ANOVA and Tukey post-hoc test.
Results: Results indicated that taking 5 mg/kg body weight of cyclophosphamide decreased mouse and testis weight and had a detrimental effect on the spermatogenesis process in the way that spermatogenic cell counts, and seminiferous and epididymis tubules diameter were decreased in comparison with the control and sham groups. But 100 and 150 mg/kg body weight doses of the extract with 5 mg/kg body weight of cyclophosphamide showed a significant increase (P≤0.05 and p≤0.01) on the mentioned parameters compared to the positive control group.
Conclusion: Therefore, it seems that the main component in this herb such as hypericin could decrease the detrimental effects of cyclophosphamide on mouse fertility.
Graphical Abstract
)
Keywords
Main Subjects
- Altıparmak M, Eskitaşçıoğlu T. (2018). Comparison of Systemic and Topical Hypericum Perforatum on Diabetic Surgical Wounds. J Invest Surg., 31(1): 29-37. [Crossref], [Google Scholar], [Publisher]
- Butterweck V. (2003). Mechanism of action of St John's wort in depression: what is known? CNS Drugs, 17(8): 539-62. [Crossref], [Google Scholar], [Publisher]
- Greeson J M, Sanford B, Monti DA.(2001) St. John's wort (Hypericum perforatum): a review of the current pharmacological, toxicological, and clinical literature. Psychopharmacology (Berl). 153(4): 402-14. [Crossref], [Google Scholar], [Publisher]
- Neary J T, Bu Y. (1999). Hypericum LI 160 inhibits uptake of serotonin and norepinephrine in astrocytes. Brain Res., 816(2): 358-63. [Crossref], [Google Scholar], [Publisher]
- Stojanović N M, Radulović N S, Randjelović P J, Laketić D. (2016). Antinociceptive Properties of St. John's Wort (Hypericum perforatum) and Other Hypericum Species. Nat Prod Commun, 11(11): 1741-1747. [Crossref], [Google Scholar], [Publisher]
- Süntar I P, Akkol E K, Yılmazer D, Baykal T, Kırmızıbekmez H, Alper M, Yeşilada E. (2010). Investigations on the in vivo wound healing potential of Hypericum perforatum L. J Ethnopharmacol, 127(2): 468-77. [Crossref], [Google Scholar], [Publisher]
- Wurglics M, Schubert-Zsilavecz M. (2006). Hypericum perforatum: a 'modern' herbal antidepressant: pharmacokinetics of active ingredients. Clin Pharmacokinet, 45(5): 449-68. [Crossref], [Google Scholar], [Publisher]
- Zhou W, Yang S, Zhang Q, Xiao R, Li B, Wang D, Niu J, Wang S, Wang Z. (2021). Functional Characterization of Serotonin N-Acetyltransferase Genes (SNAT1/2) in Melatonin Biosynthesis of Hypericum perforatum. Front Plant Sci, 12: 781717. [Crossref], [Google Scholar], [Publisher]
- Linde K. (2009). St. John's wort - an overview. Forsch Komplementmed, 16(3): 146-55. [Crossref], [Google Scholar], [Publisher]
- Rizzo P, Altschmied L, Stark P, Rutten T, Gündel A, Scharfenberg S, Franke K, Bäumlein H, Wessjohann L, Koch M, Borisjuk L, Sharbel T F. (2019). Discovery of key regulators of dark gland development and hypericin biosynthesis in St. John's Wort (Hypericum perforatum). Plant Biotechnol J., 17(12): 2299-2312. [Crossref], [Google Scholar], [Publisher]
- Revuru B, Bálintová M, Henzelyová J, Čellárová E, Kusari S. (2020). MALDI-HRMS Imaging Maps the Localization of Skyrin, the Precursor of Hypericin, and Pathway Intermediates in Leaves of Hypericum Species. Molecules, 25(17): 3964. [Crossref], [Google Scholar], [Publisher]
- Mills K A, Chess-Williams R, McDermott C. (2019). Novel insights into the mechanism of cyclophosphamide-induced bladder toxicity: chloroacetaldehyde's contribution to urothelial dysfunction in vitro. Arch Toxicol., 93(11): 3291-3303. [Crossref], [Google Scholar], [Publisher]
- Korkmaz A, Topal T, Oter S. (2007). Pathophysiological aspects of cyclophosphamide and ifosfamide induced hemorrhagic cystitis; implication of reactive oxygen and nitrogen species as well as PARP activation. Cell Biol Toxicol., 23(5): 303-12 [Crossref], [Google Scholar], [Publisher]
- Ogino M H, Tadi P. (2022). Cyclophosphamide, StatPearls Publishing, Treasure Island (FL). [Google Scholar], [Publisher]
- Meistrich M L, Wilson G, Brown B W, Da Cunha M F, Lipshultz L I. (1992). Impact of cyclophosphamide on long-term reduction in sperm count in men treated with combination chemotherapy for Ewing and soft tissue Cancer,. 70(11): 2703-12. [Crossref], [Google Scholar], [Publisher]
- Hao X, Anastácio A, Viñals-Ribé L, Lacuesta A S, Diakaki C, Alonso de Mena S, Liu K, Kenny A. (2021). Rodriguez-Wallbergcorresponding author. Follicle Rescue From Prepubertal Ovaries After Recent Treatment With Cyclophosphamide-An Experimental Culture System Using Mice to Achieve Mature Oocytes for Fertility Preservation. Front Oncol,. 11: 682470 [Crossref], [Google Scholar], [Publisher]
- Özbilgin M. K, Demirören S, Üçöz M, Oztatlici M (2021). Cyclophosphamide suppresses spermatogenesis in the testis of mice through downregulation of miR-34b and miR-34c. Andrologia,. 53(7): [Crossref], [Google Scholar], [Publisher]
- Liu X, Li Q, Wang Z, Liu F. (2021). Identification of abnormal protein expressions associated with mouse spermatogenesis induced by cyclophosphamide. J Cell Mol Med., 25(3): 1624- [Crossref], [Google Scholar], [Publisher]
- Abdul Razak R N H, Ismail F, Lokman M, Abdul Wahab A Y, Muhammad H, Ramli R, Raja Ismail R A S. (2019). Ameliorative Effects of Aquilaria malaccensis Leaves Aqueous Extract on Reproductive Toxicity Induced by Cyclophosphamide in Male Rats. Malays J Med Sci, 26(1): 44-57. [Crossref], [Google Scholar], [Publisher]
- Sadeghzadeh F, Sadeghzadeh A, Changizi-Ashtiyani S, Bakhshi S, Jalali Mashayekhi F, Mashayekhi M, Poorcheraghi H, Zarei A, Jafari M. (2020). The effect of hydro-alcoholic extract of Ceratonia Silique L. on spermatogenesis index in rats treated with cyclophosphamide: An experimental study. Int J Reprod Biomed., 18(4): 295-306. [Crossref], [Google Scholar], [Publisher]
- Mahmoudi M, Semnani Morteza K, Saeedi M, Javanmardi A. (2006). Anti-Inflammatory, Analgesic Activity, Acute Toxicity And Hypericins Content Of Iranian Hypericum Perforatum. Babol. Univ. Med. Sci., 8(4): 7-14. [Google Scholar], [Publisher]
- Kaplan H M, Doran F. (2017). Hypericum Perforatum Extract inhibits Cigarette Smoke Induced Lung Inflammation. Biological and Chemical Research, 35-43. [Google Scholar], [Publisher]
- Mohseni Kouchesfahani H, Parivar K, Hayati Roudbari N. (2006). Surveying The Effects of Hypericum Perforatum on Balb/C Rats' Med. Sci. J. Islam. Azad Univ., 16(2): 79-83. [Google Scholar], [Publisher]
- Hammami I, Ali R B, Nahdi A, Kallech-Ziri O, Boussada M, El May A, El Maya M V. (2017). Chronic consumption of Hypericum humifusum leaf extracts impairs epididymis spermatozoa characters in association with oxidative stress in adult male Wistar rats. Biomed Pharmacother, 93: 616-625. [Crossref], [Google Scholar], [Publisher]
- Alahmad A, Alghoraibi I, Zein R, Kraft S, Dräger G, Walter J G, Scheper T. (2022). Identification of Major Constituents of Hypericum perforatum L. Extracts in Syria by Development of a Rapid, Simple, and Reproducible HPLC-ESI-Q-TOF MS Analysis and Their Antioxidant Activities. ACS Omega, 7(16): 13475- [Crossref], [Google Scholar], [Publisher]
- Najafzadeh H, Erfanimajd N, Gouraninejad S, Haghighat F. (2014) Evalution of Hypericin Effect on Rat Ovulation. IJMAPR, 29(4): 721-731. [Crossref], [Google Scholar], [Publisher]
)
