Influence of Ascorbic Acid on Di-(2-Ethylhexyl) Phthalate-induced Ovarian Gene Alterations in Pubertal Female Wistar Rats

Shifana Ali, Ahmed Ziyad, Karkala Sreedhara Ranganath Pai,Anju Muraleedharan, Adhithya Gopan,Raghavendra Upadhya,Raviraja N Seetharam,Kalaivani Manokaran

Journal of Pharmacology and Pharmacotherapeutics(2024)

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摘要
Background: Di-(2-ethylhexyl) phthalate (DEHP), a plasticizer compound affecting female reproduction, leads to scenarios, such as polycystic ovarian syndrome (PCOS) and infertility through oxidative stress (OS) mechanisms. Ascorbic acid (AA) is one of the antioxidants in infertility issues. Objectives: The present study investigates the ameliorative effect of AA on DEHP-induced ovarian toxicity in pubertal female Wistar rats. Materials and methods: Thirty female Wistar rats of four weeks of age were stratified into five groups. Group I was treated with corn oil (Vehicle), groups II and III with low and high dose DEHP, and groups IV and V with low and high dose DEHP+AA were administered for 30 days. Results: Increased body weight gain was noted in DEHP groups. Estradiol hormone was considerably reduced, whereas progesterone levels were increased in both low- and high-dose DEHP-treated groups. DEHP+AA groups have shown significant ( p < 0.005) protection of these hormone levels as equal to the control group. The high-dose DEHP group shows an increased, ovarian estrogen receptor (ER) alpha, ER-beta, and progesterone receptor gene expression, and DEHP+AA groups have significantly ( p < 0.005) showed expression similar to the control. OS was noted with decreased superoxide dismutase and increased malondialdehyde expression in Group III (GR III) compared to control, whereas the DEHP+AA treated group significantly protected OS by restoring the expression levels. DEHP-treated groups show elevated levels of both Bcl-2 and BAX which is specific to apoptotic expression and restored by AA treatment ( p < 0.005). Conclusion: Evidence suggests that AA may protect against DEHP-induced ovarian toxicity by decreasing OS levels, improving folliculogenesis, and restoring the hormonal with receptor level alterations.
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