Ascorbic acid alleviates reproductive toxicity of di-(2-ethyl hexyl) phthalate in female Wistar rats

Abstract

Objective: To investigate the potential of ascorbic acid in mitigating reproductive toxicity induced by di-(2-ethyl hexyl) phthalate (DEHP) in female Wistar rats, focusing on oxidative stress, hormone levels, and gonadotropin receptors expression.

Methods: Forty female Wistar rats [30 days old, weighing (60±10)g] were randomly divided into five groups (n=8 per group). Group 1 received corn oil (control). Groups 2 and 3 were administered DEHP at 10 and 100 mg/kg body weight (b.wt.), respectively. Groups 4 and 5 received DEHP at 10 and 100 mg/ kg b.wt., respectively, plus ascorbic acid 100 mg/kg b.wt.. All treatments were given orally for 30 days. Blood and ovarian tissues were collected to assess serum reproductive hormones, gonadotropin receptor gene expression, oxidative stress markers, and apoptosis.

Results: DEHP, particularly at the higher dose, significantly decreased hormone levels (follicle-stimulating hormone, luteinizing hormone, estradiol) and gonadotropin receptor gene expression (FSHR, LHR), while increasing oxidative stress and apoptosis. Co-treatment with ascorbic acid significantly improved these parameters, reducing oxidative stress and apoptosis, and restoring hormone levels and gonadotropin receptor expression. Histopathology revealed fewer atretic follicles and less disruption in ovarian structure in DEHP and ascorbic acid-treated groups compared to those treated with DEHP alone.

Conclusions: Ascorbic acid demonstrates protective effects against DEHP-induced reproductive toxicity in female rats, likely through mitigating oxidative stress and normalizing hormone levels and ovarian function.

Keywords

Di-(2-ethylhexyl) phthalate / Ascorbic acid / Oxidative stress / Apoptosis / Ovarian morphology

Conflict of interest statement

The authors declare no conflict of interest.

Acknowledgements

The authors gratefully acknowledge all the other faculties and technical staff of the Central Animal Research Facility, Department of Medical Laboratory Technology, Manipal Centre of Biotherapeutic Research, Department of Pharmacology, Manipal Academy of Higher Education, Manipal for smooth conductance of this research work.

Funding

The study receives no extramural funding.

Authors’ contributions

Kalaivani Manokaran, Ravi Sankar Bhaskaran, and Karkala Sreedhara Ranganath Pai contributed to conceptualization. Methodology were performed by Kalaivani Manokaran and Sachin Shetty. Investigations were carried out by Kalaivani Manokaran. The first draft of manuscript was written by Kalaivani Manokaran and all the authors commented on previous versions of the manuscript. Jayesh Mudgal and Vennila Jaganathan were involved in validation, data analysis, manuscript review and editing. Prabu Paramasivam and Dharani Abirama Sundari Shanmugam were involved in manuscript review and editing. Deepak Nayak and Sunitha Carnelio were involved in interpreting the pathological results and manuscript editing. All the authors approved the final manuscript.

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