The ameliorative effect of ellagic acid on di-(2-ethylhexyl) phthalate-induced testicular structural alterations, oxidative stress, inflammation and sperm damages in adult mice
Tóm tắt
Phthalates such as di (2-ethylhexyl) phthalate (DEHP) are well known exogenous substances, disrupting reproductive system function and structure. The current research demonstrated the effect of ellagic acid (EA) on DEHP-induced testicular injury in mice. Thirty-five healthy adult male mice were randomly divided to five groups; normal saline receiving group, DEHP (2 g/kg/day, dissolved in corn oil, p.o.) receiving group, DEHP (2 g/kg/day, dissolved in corn oil, p.o.) and EA receiving groups (25, 50 and 100 mg/kg/day, p.o.). Treatment duration of animals was 14 days. Body and testes weights and sperm characteristics and histological changes of testes were evaluated. Serum testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels were analyzed. In the testicular tissue, oxidative/nitrosative stress markers and inflammatory cytokine levels were measured. Ellagic acid significantly reduced DEHP-induced reduction of body and testes weights. The DEHP-induced reduction of spermatogonia, primary spermatocyte and sertoli cells numbers as well as reduction of sperm vitality and progressive motility were reversed by EA. Furthermore, EA inhibited DEHP-induced alterations in serum hormone levels. These effects were associated with the reduction of DEHP-induced increased level of oxidative stress and inflammatory responses. Ellagic acid considerably inhibits testicular toxicity of DEHP through reducing oxidative/nitrosative stress and inflammatory responses. Our data suggest that EA may be considered as a promising agent to inhibit male reproductive toxicity induced by endocrine disrupting chemicals such as DEHP.
Tài liệu tham khảo
Bahrami N, Goudarzi M, Hosseinzadeh A, Sabbagh S, Reiter RJ, Mehrzadi S. Evaluating the protective effects of melatonin on di(2-ethylhexyl) phthalate-induced testicular injury in adult mice. Biomed Pharmacother. 2018;108:515–23.
Kaushik A, Anand S, Bhartiya D. Altered biology of testicular VSELs and SSCs by neonatal endocrine disruption results in defective spermatogenesis, reduced fertility and tumor initiation in adult mice. Stem Cell Rev Rep. 2020;16:893–908.
Cha S, Jung K, Lee MY, Hwang YJ, Yang E, Lee S-H, et al. Nonmonotonic effects of chronic low-dose di (2-ethylhexyl) phthalate on gonadal weight and reproductive. Dev Reprod. 2018;22:85.
Wittassek M, Angerer J. Phthalates: metabolism and exposure. Int J Androl. 2008;31:131–8.
Mathieu-Denoncourt J, Wallace SJ, de Solla SR, Langlois VS. Plasticizer endocrine disruption: Highlighting developmental and reproductive effects in mammals and non-mammalian aquatic species. Gen Comp Endocrinol. 2015;219:74–88.
Cao XL. Phthalate esters in foods: sources, occurrence, and analytical methods. Compr Rev Food Sci Food Saf. 2010;9:21–43.
Food U, Adminstration D. Safety assessment of Di (2-ethylhexyl) phthalate (DEHP) released from PVC medical devices. Rockville: Center for Devices and Radiological Health, US Food and Drug Administration; 2001.
Somasundaram D, Manokaran K, Selvanesan B, Bhaskaran R. Impact of di-(2-ethylhexyl) phthalate on the uterus of adult Wistar rats. Hum Exp Toxicol. 2017;36:565–72.
Tang Z-R, Xu X-L, Deng S-L, Lian Z-X, Yu K. Oestrogenic endocrine disruptors in the placenta and the fetus. Int J Mol Sci. 2020;21:1519.
Kasahara E, Sato EF, Miyoshi M, Konaka R, Hiramoto K, Sasaki J, et al. Role of oxidative stress in germ cell apoptosis induced by di (2-ethylhexyl) phthalate. Biochem J. 2002;365:849–56.
Bahrami N, Mehrzadi S, Goudarzi M, Mansouri E, Fatemi I. Lycopene abrogates di-(2-ethylhexyl) phthalate induced testicular injury by modulating oxidative, endocrine and inflammatory changes in mice. Life Sci. 2018;207:265–71.
Farbood Y, Sarkaki A, Dianat M, Khodadadi A, Haddad MK, Mashhadizadeh S. Ellagic acid prevents cognitive and hippocampal long-term potentiation deficits and brain inflammation in rat with traumatic brain injury. Life Sci. 2015;124:120–7.
Pandey KB, Rizvi SI. Plant polyphenols as dietary antioxidants in human health and disease. Oxidative Med Cell Longev. 2009;2:270–8.
Baeeri M, Momtaz S, Navaei-Nigjeh M, Niaz K, Rahimifard M, Ghasemi-Niri SF, et al. Molecular evidence on the protective effect of ellagic acid on phosalone-induced senescence in rat embryonic fibroblast cells. Food Chem Toxicol. 2017;100:8–23.
Hosseinzadeh A, Goudarzi M, Karimi MY, Khorsandi L, Mehrzadi S, Mombeini MA. Zingerone ameliorates gentamicin-induced nephrotoxicity in rats. Comp Clin Pathol. 2020;29:971–80.
Hosseinzadeh A, Houshmand G, Kalantar M, Khalili HR, Mehrzadi S, Goudarzi M. Neuroprotective effects of gallic acid against neurotoxicity induced by sodium arsenite in rats. Comp Clin Pathol. 2020:1–9.
Durairajanayagam D. Lifestyle causes of male infertility. Arab J Urol. 2018;16:10–20.
Moore RW, Rudy TA, Lin TM, Ko K, Peterson RE. Abnormalities of sexual development in male rats with in utero and lactational exposure to the antiandrogenic plasticizer Di(2-ethylhexyl) phthalate. Environ Health Perspect. 2001;109:229–37.
Holstein A-F, Schulze W, Davidoff M. Understanding spermatogenesis is a prerequisite for treatment. Reprod Biol Endocrinol. 2003;1:107.
Araki A, Mitsui T, Goudarzi H, Nakajima T, Miyashita C, Itoh S, et al. Prenatal di (2-ethylhexyl) phthalate exposure and disruption of adrenal androgens and glucocorticoids levels in cord blood: The Hokkaido Study. Sci Total Environ. 2017;581:297–304.
Noriega NC, Howdeshell KL, Furr J, Lambright CR, Wilson VS, Gray LE Jr. Pubertal administration of DEHP delays puberty, suppresses testosterone production, and inhibits reproductive tract development in male Sprague-Dawley and Long-Evans rats. Toxicol Sci. 2009;111:163–78.
Li X, Fang EF, Scheibye-Knudsen M, Cui H, Qiu L, Li J, et al. Di-(2-ethylhexyl) phthalate inhibits DNA replication leading to hyperPARylation, SIRT1 attenuation and mitochondrial dysfunction in the testis. Sci Rep. 2014;4:6434.
Wang J, Zhao T, Chen J, Kang L, Wei Y, Wu Y, et al. Multiple transcriptomic profiling: p53 signaling pathway is involved in DEHP-induced prepubertal testicular injury via promoting cell apoptosis and inhibiting cell proliferation of Leydig cells. J Hazard Mater. 2021;406:124316.
Fu G, Dai J, Li Z, Chen F, Liu L, Yi L, et al. The role of STAT3/p53 and PI3K-Akt-mTOR signaling pathway on DEHP-induced reproductive toxicity in pubertal male rat. Toxicol Appl Pharmacol. 2020;404:115151.
Huang L-P, Lee C-C, Fan J-P, Kuo P-H, Shih T-S, Hsu P-C. Urinary metabolites of di (2-ethylhexyl) phthalate relation to sperm motility, reactive oxygen species generation, and apoptosis in polyvinyl chloride workers. Int Arch Occup Environ Health. 2014;87:635–46.
Hamza RZ, Al-Baqami NM. Testicular protective effects of ellagic acid on monosodium glutamate-induced testicular structural alterations in male rats. Ultrastruct Pathol. 2019;43:170–83.
Mehrzadi S, Bahrami N, Mehrabani M, Motevalian M, Mansouri E, Goudarzi M. Ellagic acid: A promising protective remedy against testicular toxicity induced by arsenic. Biomed Pharmacother. 2018;103:1464–72.
Çeribaşı AO, Sakin F, Türk G, Sönmez M, Ateşşahin A. Impact of ellagic acid on adriamycin-induced testicular histopathological lesions, apoptosis, lipid peroxidation and sperm damages. Exp Toxicol Pathol. 2012;64:717–24.
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.
Yang H-L, Lin C-P, Vudhya Gowrisankar Y, Huang P-J, Chang W-L, Shrestha S, et al. The anti-melanogenic effects of ellagic acid through induction of autophagy in melanocytes and suppression of UVA-activated α-MSH pathways via Nrf2 activation in keratinocytes. Biochem Pharmacol. 2021;185:114454.
Nishioka J, Iwahara C, Kawasaki M, Yoshizaki F, Nakayama H, Takamori K, et al. Di-(2-ethylhexyl) phthalate induces production of inflammatory molecules in human macrophages. Inflamm Res. 2012;61:69–78.
Naito M, Terayama H, Hirai S, Qu N, Lustig L, Itoh M. Experimental autoimmune orchitis as a model of immunological male infertility. Med Molec Morphol. 2012;45:185–9.
Stenz L, Escoffier J, Rahban R, Nef S, Paoloni-Giacobino A. Testicular dysgenesis syndrome and long-lasting epigenetic silencing of mouse sperm genes involved in the reproductive system after prenatal exposure to DEHP. PLoS One. 2017;12:e0170441.
Hirai S, Naito M, Kuramasu M, Ogawa Y, Terayama H, Qu N, et al. Low-dose exposure to di-(2-ethylhexyl) phthalate (DEHP) increases susceptibility to testicular autoimmunity in mice. Reprod Biol. 2015;15:163–71.
Ahad A, Ganai AA, Mujeeb M, Siddiqui WA. Ellagic acid, an NF-κB inhibitor, ameliorates renal function in experimental diabetic nephropathy. Chem Biol Interact. 2014;219:64–75.