Abstract

BackgroundPhthalates 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.MethodsThirty-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.ResultsEllagic 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.ConclusionsEllagic 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.

Highlights

  • Phthalates such as di (2-ethylhexyl) phthalate (DEHP) are well known exogenous substances, disrupting reproductive system function and structure

  • Effects of ellagic acid (EA) on di(2-ethylhexyl) phthalate (DEHP)‐induced alterations in body and testes weights Exposure of mice with DEHP resulted in the significant reduction of body and testes weights compared to the control group (p < 0.05)

  • EA ameliorated DEHP-induced MDA, NO, protein carbonylation (PC) and MPO levels and increased the capacity of antioxidants. These results suggested that EA may improve testicular cell function through reducing DEHP-induced oxidative stress; these effects may inhibit the degeneration of Leydig and Sertoli cells leading to the improvement of testosterone level, and sperm count and motility

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Summary

Introduction

Phthalates such as di (2-ethylhexyl) phthalate (DEHP) are well known exogenous substances, disrupting reproductive system function and structure. Phthalates are well known exogenous substances, which have disrupting effect on reproductive system. Among various types of phthalates, the most male reproductive toxicity is reported for DEHP [3, 4]. This phthalate derivative is frequently used as plasticizer in the manufacture of polyvinyl chloride plastics to render more flexible final products. Animal studies report that DEHP has hazardous effect on male reproductive system through suppressing testosterone biosynthesis leading to the tubular atrophy and testicular degeneration [1]. Antioxidant agents seem to be useful to reduce DEHP toxicity in reproductive system [11]

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