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

Shifana Ali, Ahmed Ziyad, K. S. R. Pai, Anju Muraleedharan, Adhithya Gopan, Raghavendra Upadhya, R. Seetharam, K. Manokaran
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Abstract

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. The present study investigates the ameliorative effect of AA on DEHP-induced ovarian toxicity in pubertal female Wistar rats. 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. 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). 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.
抗坏血酸对邻苯二甲酸二(2-乙基己基)酯诱导的青春期雌性 Wistar 大鼠卵巢基因改变的影响
邻苯二甲酸二(2-乙基己基)酯(DEHP)是一种影响女性生殖的增塑剂化合物,通过氧化应激(OS)机制导致多囊卵巢综合症(PCOS)和不孕症等情况。抗坏血酸(AA)是治疗不孕症的抗氧化剂之一。本研究调查了 AA 对 DEHP 诱导的青春期雌性 Wistar 大鼠卵巢毒性的改善作用。将 30 只四周龄的雌性 Wistar 大鼠分为五组。I 组使用玉米油(载体),II 组和 III 组使用低剂量和高剂量 DEHP,IV 组和 V 组使用低剂量和高剂量 DEHP+AA,连续用药 30 天。DEHP 组的体重增加。低剂量和高剂量 DEHP 组的雌二醇激素水平显著下降,而孕酮水平上升。与对照组相比,DEHP+AA 组对这些激素水平有明显的保护作用(p < 0.005)。高剂量 DEHP 组显示卵巢雌激素受体(ER)α、ER-β 和孕酮受体基因表达增加,而 DEHP+AA 组则显示与对照组相似的基因表达(p < 0.005)。与对照组相比,第 III 组(GR III)的超氧化物歧化酶减少,丙二醛表达增加,而 DEHP+AA 处理组通过恢复表达水平显著保护了 OS。DEHP处理组的Bcl-2和BAX水平升高,这是凋亡表达的特异性表现,经AA处理后得到恢复(P < 0.005)。有证据表明,AA可通过降低OS水平、改善卵泡生成和恢复激素与受体水平的改变来防止DEHP诱导的卵巢毒性。
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