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Saleh, S., Ghanaatpisheh, A., Haghshenas, H., Parvin, N., Mikaeiliagah, E., Kargar Jahromi, H., & Ebrahimi, B. (2023). The effect of leaf hydroalcoholic extract of Ephedra pachyclada infertility in male rats treated with cyclophosphamide: An experimental study. International Journal of Reproductive BioMedicine (IJRM), 21(4), 285–294. https://doi.org/10.18502/ijrm.v21i4.13268
https://doi.org/10.18502/ijrm.v21i4.13268
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authors
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Shiva Saleh
Shiva Saleh
Student Research Committee, Jahrom University of Medical Sciences, Jahrom, Iran.
-
Aref Ghanaatpisheh
Aref Ghanaatpisheh
Student Research Committee, Jahrom University of Medical Sciences, Jahrom, Iran.
-
Hoda Haghshenas
Hoda Haghshenas
Student Research Committee, Jahrom University of Medical Sciences, Jahrom, Iran
-
Negar Parvin
Negar Parvin
Student Research Committee, Jahrom University of Medical Sciences, Jahrom, Iran
-
Elmira Mikaeiliagah
Elmira Mikaeiliagah
Stem Cell and Tissue Engineering Laboratory, Department of Orthopedics, West Virginia University, Morgantown, USA.
-
Hossein Kargar Jahromi
Hossein Kargar Jahromi
Research Center for Noncommunicable Diseases, Jahrom University of Medical Sciences, Jahrom, Iran.
-
Bahare Ebrahimi
Bahare Ebrahimi
Shiraz Geriatric Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Published Date
- May 6, 2023
The effect of leaf hydroalcoholic extract of Ephedra pachyclada infertility in male rats treated with cyclophosphamide: An experimental study
Abstract
Background: Cyclophosphamide (CP) has clinical applications in treating diverse malignancies and autoimmune disorders; at the same time, it also has harmful effects on the body tissues, particularly the genitals. The most significant side effects of CP are changing the reproductive system’s function and infertility.
Objective: This study determines the Ephedra hydroalcoholic extract (EP) role on testicular tissue and the pituitary-gonadal axis in CP-treated male rats.
Materials and Methods: In this experimental study, 48 adult Wistar rats were separated into 6 groups (n = 8/each): control, sham, CP recipients, and CP recipients with gavage-fed EP (250, 500, and 1000 mg/kg). On the 29th day, the blood of the weighed animals’ was drawn from their heart, and serum concentrations of follicle-stimulating hormone, luteinizing hormone, and testosterone were measured. After preparing testicular tissue segments, cells were counted.
Results: While CP decreased follicle-stimulating hormone, luteinizing hormone, and testosterone levels (p < 0.05), the use of EP changed them and even reached the control. Serum gonadotropin-releasing hormone increased significantly in all EP groups compared to the control and CP groups. Compared to the control, a significant decrease in Total antioxidant capacity and plasma glutathione peroxidase was observed in the CP groups. EP (all doses) significantly increased their concentration compared to the CP group (p < 0.05); significant reduction in serum total oxidant status and malondialdehyde in CP groups changed by EP (p < 0.05). Although CP’s role on spermatogonia counts (57.5 ± 5.2 in CP, 67.1 ± 6.0 in control), higher doses of EP had no significant effect on this but did affect spermatocyte and spermatid cells count.
Conclusion: Due to its antioxidant characteristics, EP mitigated the effects of CP on the investigated parameters in rats.
Key words: Ephedra, Cyclophosphamide, Cancer, Spermatogenesis, Sex hormones, ROS.
References
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[4] Sinanoglu O, Yener AN, Ekici S, Midi A, Aksungar FB. The protective effects of spirulina in cyclophosphamide induced nephrotoxicity and urotoxicity in rats. Urology 2012; 80: 1392. e1–e6.
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[8] Qin W-S, Deng Y-H, Cui FC. Sulforaphane protects against acrolein-induced oxidative stress and inflammatory responses: Modulation of Nrf-2 and COX-2 expression. Arch Med Sci 2016; 12: 871–880.
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[10] Aitken RJ, Whiting S, De Iuliis GN, McClymont S, Mitchell LA, Baker MA. Electrophilic aldehydes generated by sperm metabolism activate mitochondrial reactive oxygen species generation and apoptosis by targeting succinate dehydrogenase. J Biol Chem 2012; 287: 33048–33060.
[11] Harward LE, Mitchell K, Pieper C, Copland S, Criscione-Schreiber LG, Clowse MEB. The impact of cyclophosphamide on menstruation and pregnancy in women with rheumatologic disease. Lupus 2013; 22: 81–86.
[12] Fusco R, Trovato Salinaro A, Siracusa R, D’Amico R, Impellizzeri D, Scuto M, et al. Hidrox(®) counteracts cyclophosphamide-induced male infertility through NRF2 pathways in a mouse model. Antioxidants (Basel) 2021; 10: 778.
[13] Watcho P, Mpeck IR, Deeh Defo PB, Wankeu-Nya M, Ngadjui E, Bonsou Fozin GR, et al. Cyclophosphamideinduced reproductive toxicity: Beneficial effects of Helichrysum odoratissimum (Asteraceae) in male Wistar rats. J Integr Med 2019; 17: 366–373.
[14] Bakhtiary Z, Shahrooz R, Ahmadi A, Zarei L. Evaluation of antioxidant effects of crocin on sperm quality in cyclophosphamide treated adult mice. Vet Res Forum 2014; 5: 213–218.
[15] Ghobadi E, Moloudizargari M, Asghari MH, Abdollahi M. The mechanisms of cyclophosphamide-induced testicular toxicity and the protective agents. Expert Opin Drug Metab Toxicol 2017; 13: 525–536.
[16] Can S, Yildiz SC, Keskin C, Şahintürk V, Cengiz M, Appak Başköy S, et al. Investigation into the protective effects of Hypericum Triquetrifolium Turra seed against cyclophosphamide-induced testicular injury in Sprague Dawley rats. Drug Chem Toxicol 2022; 45: 1679–1686.
[17] González-Juárez DE, Escobedo-Moratilla A, Flores J, Hidalgo-Figueroa S, Martínez-Tagüeña N, MoralesJiménez J, et al. A review of the Ephedra genus: Distribution, ecology, ethnobotany, phytochemistry and pharmacological properties. Molecules 2020; 25: 3283.
[18] Sioud F, Toumia IB, Lahmer A, Khlifi R, Dhaouefi Z, Maatouk M, et al. Methanolic extract of Ephedra alata ameliorates cisplatin-induced nephrotoxicity and hepatotoxicity through reducing oxidative stress and genotoxicity. Environ Sci Pollut Res Int 2020; 27: 12792– 12801.
[19] Danciu C, Muntean D, Alexa E, Farcas C, Oprean C, Zupko I, et al. Phytochemical characterization and evaluation of the antimicrobial, antiproliferative and pro-apoptotic potential of Ephedra alata Decne. Hydroalcoholic extract against the MCF-7 breast cancer cell line. Molecules 2018; 24: 13.
[20] Al-saraireh YM, Youssef AMM, Alshammari FOFO, AlSarayreh SA, Al-Shuneigat JM, Alrawashdeh HM, et al. Phytochemical characterization and anti-cancer properties of extract of Ephedra foeminea (Ephedraceae) aerial parts. Trop J Pharm Res 2021; 20: 1675–1681.
[21] Rustaiyan A, Javidnia K, Farjam MH, Aboee-Mehrizi F, Ezzatzadeh E. Antimicrobial and antioxidant activity of the Ephedra sarcocarpa growing in Iran. J Med Plant Res 2011; 5: 4251–4255.
[22] Gul R, Jan SU, Faridullah S, Sherani S, Jahan N. Preliminary phytochemical screening, quantitative analysis of alkaloids, and antioxidant activity of crude plant extracts from Ephedra intermedia indigenous to Balochistan. Sci World J 2017; 2017: 5873648.
[23] Fu Y, Yuan P, Zheng Y, Gao L, Wei Y, Chen Y, et al. Ephedra herb reduces adriamycin-induced testicular toxicity by upregulating the gonadotropin-releasing hormone signalling pathway. Biomed Pharmacother 2022; 150: 113061.
[24] Ghasemi Pirbalouti A, Amirmohammadi M, Azizi Sh, Craker L. Healing effect of hydro-alcoholic extract of Ephedra pachyclada Boiss. In experimental gastric ulcer in rat. Acta Pol Pharm 2013; 70: 1003–1009.
[25] Alizadeh Behbahani B, Falah F, Lavi Arab F, Vasiee M, Tabatabaee Yazdi F. Chemical composition and antioxidant, antimicrobial, and antiproliferative activities of Cinnamomum zeylanicum bark essential oil. Evid Based Complement Alternat Med 2020; 2020: 5190603.
[26] Dharmadasa RM, Abeysinghe DC, Dissanayake DMN, Abeywardhane KW, Fernando NS. Leaf essential oil composition, antioxidant activity, total phenolic content and total flavonoid content of Pimenta dioica (L.) Merr (Myrtaceae): A superior quality spice grown in Sri Lanka. Univers J Agric Res. 2015; 3: 49–52.
[27] Marcozzi S, Rossi V, Salvatore G, Di Rella F, De Felici M, Klinger FG. Distinct effects of epirubicin, cisplatin and cyclophosphamide on ovarian somatic cells of prepuberal ovaries. Aging (Albany NY) 2019; 11: 10532–10556.
[28] Unal F, Yuksel MA, Boran B, Temel Yuksel I, Abali R. The role of N-Acetylcysteine in preventing cyclophosphamideinduced gonadotoxicity: An experimental study in rats. J Obstet Gynaecol 2016; 36: 372–375.
[29] Iqubal A, Sharma S, Ansari MA, Najmi AK, Syed MA, Ali J, et al. Nerolidol attenuates cyclophosphamide-induced cardiac inflammation, apoptosis and fibrosis in Swiss Albino mice. Eur J Pharmacol 2019; 863: 172666.
[30] Jeelani R, Khan SN, Shaeib F, Kohan-Ghadr HR, Aldhaheri SR, Najafi T, et al. Cyclophosphamide and acrolein induced oxidative stress leading to deterioration of metaphase II mouse oocyte quality. Free Radic Biol Med 2017; 110: 11– 18.
[31] Wang Y, Zou Z, Jaisi A, Olatunji OJ. Unravelling the protective effects of emodin against cyclophosphamide induced gonadotoxicity in male Wistar rats. Drug Des Devel Ther 2021; 15: 4403–4411.
[32] Briseño-Bugarín J, Hernández-Ochoa I, Araujo-Padilla X, Mojica-Villegas MA, Montaño-González RI, GutiérrezSalmeán G, et al. Phycobiliproteins ameliorate gonadal toxicity in male mice treated with cyclophosphamide. Nutrients 2021; 13: 2616.
[33] Khan A, Jan G, Khan A, Jan FG, Bahadur A, Danish M. In vitro antioxidant and antimicrobial activities of Ephedra gerardiana (root and stem) crude extract and fractions. Evid Based Complement Alternat Med 2017; 2017: 4040254.
[34] Abu Hajleh MN, Khleifat KM, Alqaraleh M, Al-Hraishat E, Al-Limoun MO, Qaralleh H, et al. Antioxidant and antihyperglycemic effects of Ephedra foeminea aqueous extract in streptozotocin-induced diabetic rats. Nutrients 2022; 14: 2338.
[35] Creasy DM, Chapin RE. Male reproductive system. In: Haschek WM, Rousseau CG, Wallig MA. Haschek and Rousseaux’s handbook of toxicologic pathology. Netherlands: Elsevier Academic Press; 2013: 2493–2598.
[36] Agarwal A, Virk G, Ong C, du Plessis SS. Effect of oxidative stress on male reproduction. World J Men’s Health 2014; 32: 1–17.
[37] Aitken RJ, Smith TB, Jobling MS, Baker MA, De Iuliis GN. Oxidative stress and male reproductive health. Asian J Androl 2014; 16: 31–38.
[38] Potnuri AG, Allakonda L, Lahkar M. Crocin attenuates cyclophosphamide induced testicular toxicity by preserving glutathione redox system. Biomed Pharmacother 2018; 101: 174–180.
[39] Ebokaiwe AP, Obasi DO, Njoku RC, Osawe S. Cyclophosphamide-induced testicular oxidativeinflammatory injury is accompanied by altered immunosuppressive indoleamine 2, 3-dioxygenase in Wister rats: Influence of dietary quercetin. Andrologia 2022; 54: e14341.
[40] Ebrahimi B, Matavos-Aramyan H, Keshtgar S. The cryoprotective effect of vitamins on human spermatozoa quality: A systematic review and meta-analysis. Cell Tissue Bank 2022; 23: 213–225.
[41] Veskoukis AS, Tsatsakis AM, Kouretas D. Dietary oxidative stress and antioxidant defense with an emphasis on plant extract administration. Cell Stress Chaperones 2012; 17: 11–21.
[42] Abu-Risha SE, Mousa MA, Elsisi AE. Protective role of irbesartan against cyclophosphamide-induced testicular damage in rats via up-regulating PPAR-γ signaling and ameliorating NF-κB/NLRP3/IL-18 inflammatory axis. Life Sci 2022; 289: 120218.
[43] Poojary KK, Nayak G, Vasani A, Kumari S, Dcunha R, Kunhiraman JP, et al. Curcumin nanocrystals attenuate cyclophosphamide-induced testicular toxicity in mice. Toxicol Appl Pharmacol 2021; 433: 115772.
[44] Barik G, Chaturvedula L, Bobby Z. Role of oxidative stress and antioxidants in male infertility: An interventional study. J Hum Reprod Sci 2019; 12: 204–209.
[2] Gagelmann N, Bacigalupo A, Rambaldi A, Hoelzer D, Halter J, Sanz J, et al. Haploidentical stem cell transplantation with posttransplant cyclophosphamide therapy vs other donor transplantations in adults with hematologic cancers: A systematic review and metaanalysis. JAMA Oncol 2019; 5: 1739–1748.
[3] Iqubal A, Iqubal MK, Sharma S, Ansari MA, Najmi AK, Ali SM, et al. Molecular mechanism involved in cyclophosphamide-induced cardiotoxicity: Old drug with a new vision. Life Sci 2019; 218: 112–131.
[4] Sinanoglu O, Yener AN, Ekici S, Midi A, Aksungar FB. The protective effects of spirulina in cyclophosphamide induced nephrotoxicity and urotoxicity in rats. Urology 2012; 80: 1392. e1–e6.
[5] Akomolafe SF, Aluko BT. Protective effect of curcumin on fertility in cyclophosphamide exposed rats: Involvement of multiple pathways. J Food Biochem 2020; 44: e13095.
[6] Nagappa M, Netravathi M, Taly AB, Sinha S, Bindu PS, Mahadevan A. Long-term efficacy and limitations of cyclophosphamide in myasthenia gravis. J Clin Neurosci 2014; 21: 1909–1914.
[7] Iqubal A, Syed MA, Najmi AK, Ali J, Haque SE. Ameliorative effect of nerolidol on cyclophosphamide-induced gonadal toxicity in Swiss Albino mice: Biochemical-, histologicaland immunohistochemical-based evidences. Andrologia 2020; 52: e13535.
[8] Qin W-S, Deng Y-H, Cui FC. Sulforaphane protects against acrolein-induced oxidative stress and inflammatory responses: Modulation of Nrf-2 and COX-2 expression. Arch Med Sci 2016; 12: 871–880.
[9] Esfandyari S, Aleyasin A, Noroozi Z, Taheri M, Khodarahmian M, Eslami M, et al. The protective effect of sulforaphane against oxidative stress through activation of Nrf2/ARE pathway in human granulosa cells. Cell J 2021; 23: 692–700.
[10] Aitken RJ, Whiting S, De Iuliis GN, McClymont S, Mitchell LA, Baker MA. Electrophilic aldehydes generated by sperm metabolism activate mitochondrial reactive oxygen species generation and apoptosis by targeting succinate dehydrogenase. J Biol Chem 2012; 287: 33048–33060.
[11] Harward LE, Mitchell K, Pieper C, Copland S, Criscione-Schreiber LG, Clowse MEB. The impact of cyclophosphamide on menstruation and pregnancy in women with rheumatologic disease. Lupus 2013; 22: 81–86.
[12] Fusco R, Trovato Salinaro A, Siracusa R, D’Amico R, Impellizzeri D, Scuto M, et al. Hidrox(®) counteracts cyclophosphamide-induced male infertility through NRF2 pathways in a mouse model. Antioxidants (Basel) 2021; 10: 778.
[13] Watcho P, Mpeck IR, Deeh Defo PB, Wankeu-Nya M, Ngadjui E, Bonsou Fozin GR, et al. Cyclophosphamideinduced reproductive toxicity: Beneficial effects of Helichrysum odoratissimum (Asteraceae) in male Wistar rats. J Integr Med 2019; 17: 366–373.
[14] Bakhtiary Z, Shahrooz R, Ahmadi A, Zarei L. Evaluation of antioxidant effects of crocin on sperm quality in cyclophosphamide treated adult mice. Vet Res Forum 2014; 5: 213–218.
[15] Ghobadi E, Moloudizargari M, Asghari MH, Abdollahi M. The mechanisms of cyclophosphamide-induced testicular toxicity and the protective agents. Expert Opin Drug Metab Toxicol 2017; 13: 525–536.
[16] Can S, Yildiz SC, Keskin C, Şahintürk V, Cengiz M, Appak Başköy S, et al. Investigation into the protective effects of Hypericum Triquetrifolium Turra seed against cyclophosphamide-induced testicular injury in Sprague Dawley rats. Drug Chem Toxicol 2022; 45: 1679–1686.
[17] González-Juárez DE, Escobedo-Moratilla A, Flores J, Hidalgo-Figueroa S, Martínez-Tagüeña N, MoralesJiménez J, et al. A review of the Ephedra genus: Distribution, ecology, ethnobotany, phytochemistry and pharmacological properties. Molecules 2020; 25: 3283.
[18] Sioud F, Toumia IB, Lahmer A, Khlifi R, Dhaouefi Z, Maatouk M, et al. Methanolic extract of Ephedra alata ameliorates cisplatin-induced nephrotoxicity and hepatotoxicity through reducing oxidative stress and genotoxicity. Environ Sci Pollut Res Int 2020; 27: 12792– 12801.
[19] Danciu C, Muntean D, Alexa E, Farcas C, Oprean C, Zupko I, et al. Phytochemical characterization and evaluation of the antimicrobial, antiproliferative and pro-apoptotic potential of Ephedra alata Decne. Hydroalcoholic extract against the MCF-7 breast cancer cell line. Molecules 2018; 24: 13.
[20] Al-saraireh YM, Youssef AMM, Alshammari FOFO, AlSarayreh SA, Al-Shuneigat JM, Alrawashdeh HM, et al. Phytochemical characterization and anti-cancer properties of extract of Ephedra foeminea (Ephedraceae) aerial parts. Trop J Pharm Res 2021; 20: 1675–1681.
[21] Rustaiyan A, Javidnia K, Farjam MH, Aboee-Mehrizi F, Ezzatzadeh E. Antimicrobial and antioxidant activity of the Ephedra sarcocarpa growing in Iran. J Med Plant Res 2011; 5: 4251–4255.
[22] Gul R, Jan SU, Faridullah S, Sherani S, Jahan N. Preliminary phytochemical screening, quantitative analysis of alkaloids, and antioxidant activity of crude plant extracts from Ephedra intermedia indigenous to Balochistan. Sci World J 2017; 2017: 5873648.
[23] Fu Y, Yuan P, Zheng Y, Gao L, Wei Y, Chen Y, et al. Ephedra herb reduces adriamycin-induced testicular toxicity by upregulating the gonadotropin-releasing hormone signalling pathway. Biomed Pharmacother 2022; 150: 113061.
[24] Ghasemi Pirbalouti A, Amirmohammadi M, Azizi Sh, Craker L. Healing effect of hydro-alcoholic extract of Ephedra pachyclada Boiss. In experimental gastric ulcer in rat. Acta Pol Pharm 2013; 70: 1003–1009.
[25] Alizadeh Behbahani B, Falah F, Lavi Arab F, Vasiee M, Tabatabaee Yazdi F. Chemical composition and antioxidant, antimicrobial, and antiproliferative activities of Cinnamomum zeylanicum bark essential oil. Evid Based Complement Alternat Med 2020; 2020: 5190603.
[26] Dharmadasa RM, Abeysinghe DC, Dissanayake DMN, Abeywardhane KW, Fernando NS. Leaf essential oil composition, antioxidant activity, total phenolic content and total flavonoid content of Pimenta dioica (L.) Merr (Myrtaceae): A superior quality spice grown in Sri Lanka. Univers J Agric Res. 2015; 3: 49–52.
[27] Marcozzi S, Rossi V, Salvatore G, Di Rella F, De Felici M, Klinger FG. Distinct effects of epirubicin, cisplatin and cyclophosphamide on ovarian somatic cells of prepuberal ovaries. Aging (Albany NY) 2019; 11: 10532–10556.
[28] Unal F, Yuksel MA, Boran B, Temel Yuksel I, Abali R. The role of N-Acetylcysteine in preventing cyclophosphamideinduced gonadotoxicity: An experimental study in rats. J Obstet Gynaecol 2016; 36: 372–375.
[29] Iqubal A, Sharma S, Ansari MA, Najmi AK, Syed MA, Ali J, et al. Nerolidol attenuates cyclophosphamide-induced cardiac inflammation, apoptosis and fibrosis in Swiss Albino mice. Eur J Pharmacol 2019; 863: 172666.
[30] Jeelani R, Khan SN, Shaeib F, Kohan-Ghadr HR, Aldhaheri SR, Najafi T, et al. Cyclophosphamide and acrolein induced oxidative stress leading to deterioration of metaphase II mouse oocyte quality. Free Radic Biol Med 2017; 110: 11– 18.
[31] Wang Y, Zou Z, Jaisi A, Olatunji OJ. Unravelling the protective effects of emodin against cyclophosphamide induced gonadotoxicity in male Wistar rats. Drug Des Devel Ther 2021; 15: 4403–4411.
[32] Briseño-Bugarín J, Hernández-Ochoa I, Araujo-Padilla X, Mojica-Villegas MA, Montaño-González RI, GutiérrezSalmeán G, et al. Phycobiliproteins ameliorate gonadal toxicity in male mice treated with cyclophosphamide. Nutrients 2021; 13: 2616.
[33] Khan A, Jan G, Khan A, Jan FG, Bahadur A, Danish M. In vitro antioxidant and antimicrobial activities of Ephedra gerardiana (root and stem) crude extract and fractions. Evid Based Complement Alternat Med 2017; 2017: 4040254.
[34] Abu Hajleh MN, Khleifat KM, Alqaraleh M, Al-Hraishat E, Al-Limoun MO, Qaralleh H, et al. Antioxidant and antihyperglycemic effects of Ephedra foeminea aqueous extract in streptozotocin-induced diabetic rats. Nutrients 2022; 14: 2338.
[35] Creasy DM, Chapin RE. Male reproductive system. In: Haschek WM, Rousseau CG, Wallig MA. Haschek and Rousseaux’s handbook of toxicologic pathology. Netherlands: Elsevier Academic Press; 2013: 2493–2598.
[36] Agarwal A, Virk G, Ong C, du Plessis SS. Effect of oxidative stress on male reproduction. World J Men’s Health 2014; 32: 1–17.
[37] Aitken RJ, Smith TB, Jobling MS, Baker MA, De Iuliis GN. Oxidative stress and male reproductive health. Asian J Androl 2014; 16: 31–38.
[38] Potnuri AG, Allakonda L, Lahkar M. Crocin attenuates cyclophosphamide induced testicular toxicity by preserving glutathione redox system. Biomed Pharmacother 2018; 101: 174–180.
[39] Ebokaiwe AP, Obasi DO, Njoku RC, Osawe S. Cyclophosphamide-induced testicular oxidativeinflammatory injury is accompanied by altered immunosuppressive indoleamine 2, 3-dioxygenase in Wister rats: Influence of dietary quercetin. Andrologia 2022; 54: e14341.
[40] Ebrahimi B, Matavos-Aramyan H, Keshtgar S. The cryoprotective effect of vitamins on human spermatozoa quality: A systematic review and meta-analysis. Cell Tissue Bank 2022; 23: 213–225.
[41] Veskoukis AS, Tsatsakis AM, Kouretas D. Dietary oxidative stress and antioxidant defense with an emphasis on plant extract administration. Cell Stress Chaperones 2012; 17: 11–21.
[42] Abu-Risha SE, Mousa MA, Elsisi AE. Protective role of irbesartan against cyclophosphamide-induced testicular damage in rats via up-regulating PPAR-γ signaling and ameliorating NF-κB/NLRP3/IL-18 inflammatory axis. Life Sci 2022; 289: 120218.
[43] Poojary KK, Nayak G, Vasani A, Kumari S, Dcunha R, Kunhiraman JP, et al. Curcumin nanocrystals attenuate cyclophosphamide-induced testicular toxicity in mice. Toxicol Appl Pharmacol 2021; 433: 115772.
[44] Barik G, Chaturvedula L, Bobby Z. Role of oxidative stress and antioxidants in male infertility: An interventional study. J Hum Reprod Sci 2019; 12: 204–209.