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西红花酸通过抗凋亡机制和上调 P 糖蛋白表达减轻双酚 A 诱导的大鼠睾丸毒性。

Rats' testicular toxicity induced by bisphenol A is lessened by crocin via an antiapoptotic mechanism and bumped P-glycoprotein expression.

机构信息

Biochemistry and Molecular Biology Department, Faculty of Pharmacy, Al-Azhar University, Nasr City, Cairo, 11231, Egypt; Medical Laboratory Sciences Department, Fakeeh College for Medical Sciences, Jeddah, 21461, Saudi Arabia.

Pathological Sciences Department, Fakeeh College for Medical Sciences, Jeddah, 21461, Saudi Arabia.

出版信息

Toxicon. 2024 Apr;241:107674. doi: 10.1016/j.toxicon.2024.107674. Epub 2024 Mar 6.

Abstract

Bisphenol A (BPA) engenders testicular toxicity via hydroxyl free radical genesis in rat striatum and depletion of the endogenous antioxidants in the epididymal sperms. The multi-drug resistance efflux carrier; P-glycoprotein (P-gp) expel the BPA from the testis and is responsible for the testicular protection through the deactivation of numerous xenobiotics. In our study, we investigated whether the BPA-induced testicular toxicity could be circumvented through administration of an antioxidant; crocin (Cr). Implication of P-gp expression was also investigated. Rats administered BPA (10 mg/kg b.w. orally for 14 days), dropped the body weight, testes/body weight ratio, total protein content, testosterone, follicle stimulating hormone, luteinizing hormone, and sperm motility & count, total antioxidant status, glutathione content and antioxidant enzymes (superoxide dismutase and catalase), concomitant with the elevation of the percentage abnormal sperm morphology, as well as testicular lipid peroxides and nitrite/nitrate levels. Histopathological examination showed spermatogenesis disorders after the BPA rats exposure. The immunohistochemical study showed up-regulation of the P-gp as evident by increasing immunoreactivity in interstitial cells, with positive localization in some spermatogonia cells. The BPA-treated rats showed positive immunoreactivity against caspase-3. The co-intake of Cr (200 mg/kg b.w./day, i.p. 14 days) along with the BPA, significantly ameliorated all the mentioned parameters, boosted histopathological image, fell the caspase-3 up-regulation, and perched the P-gp expression. We showed that, Cr promotes P-gp as an approach to nurture the testicles against the BPA toxicity. In conclusion; Cr lessens the oxidative stress conditions to safeguard rats from the BPA-induced testicular toxicity and sex hormones abnormalities, reducing apoptosis and up-regulating P-gp.

摘要

双酚 A (BPA) 通过在大鼠纹状体中产生羟基自由基和耗尽附睾精子中的内源性抗氧化剂,引起睾丸毒性。多药耐药外排载体; P-糖蛋白 (P-gp) 将 BPA 从睾丸中排出,并通过使许多外源性物质失活来负责睾丸保护。在我们的研究中,我们研究了通过给予抗氧化剂;藏红花酸 (Cr) 是否可以避免 BPA 引起的睾丸毒性。还研究了 P-gp 表达的含义。给予 BPA(10mg/kg b.w. 口服 14 天)的大鼠体重、睾丸/体重比、总蛋白含量、睾酮、卵泡刺激素、黄体生成素和精子活力和计数、总抗氧化状态、谷胱甘肽含量和抗氧化酶(超氧化物歧化酶和过氧化氢酶)下降,同时异常精子形态的百分比升高,以及睾丸脂质过氧化物和亚硝酸盐/硝酸盐水平升高。组织病理学检查显示 BPA 暴露后精子发生障碍。免疫组织化学研究表明 P-gp 上调,间质细胞的免疫反应性增加,一些精原细胞呈阳性定位。BPA 处理的大鼠显示 caspase-3 阳性免疫反应性。与 BPA 一起摄入藏红花酸(200mg/kg b.w./天,腹腔注射 14 天),显着改善了所有上述参数,降低了 caspase-3 的上调,并抑制了 P-gp 的表达。我们表明,Cr 促进 P-gp 作为一种滋养睾丸免受 BPA 毒性的方法。总之;Cr 减轻氧化应激条件,保护大鼠免受 BPA 引起的睾丸毒性和性激素异常,减少细胞凋亡并上调 P-gp。

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