Shahin Nancy N, Mohamed Maha M
Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Department of Home Economics, Faculty of Women for Arts, Science and Education, Ain Shams University, Cairo, Egypt.
Toxicol Appl Pharmacol. 2017 Nov 1;334:129-141. doi: 10.1016/j.taap.2017.08.014. Epub 2017 Aug 26.
This study investigated the effect of short-term oral exposure to nano-sized titanium dioxide (nTiO) on Wistar rat prostate and testis, and the associating reproductive-related alterations. The study also evaluated the potential ameliorative effect of the natural flavonoid, morin, on nTiO-induced aberrations. Intragastric administration of nTiO (50mg/kg/day for 1, 2 and 3weeks) increased testicular gamma-glutamyltransferase (γ-GT) activity and decreased testicular steroidogenic acute regulatory protein (StAR) and c-kit gene expression, serum testosterone level and sperm count. nTiO-treated rats also exhibited prostatic and testicular altered glutathione levels, elevated TNF-α levels, up-regulated Fas, Bax and caspase-3 gene expression, down-regulated Bcl-2 gene expression and enhanced prostatic lipid peroxidation. Sperm malformation and elevated testicular acid phosphatase (ACP) activity and malondialdehyde level, serum prostatic acid phosphatase activity, prostate specific antigen (PSA), gonadotrophin and estradiol levels occurred after the 2 and 3week regimens. Morin (30mg/kg/day administered intragastrically for 5weeks) mitigated nTiO-induced prostatic and testicular injury as evidenced by lowering serum PSA level, testicular γ-GT and ACP activities and TNF-α level, along with hampering both intrinsic and extrinsic apoptotic pathways. Moreover, morin alleviated prostatic lipid peroxidation, raised prostatic glutathione level, and relieved testicular reductive stress. Additionally, morin increased testicular StAR and c-kit mRNA expression, raised the sperm count, reduced sperm deformities and modified the altered hormone profile. Histopathological evaluation supported the biochemical findings. In conclusion, morin could ameliorate nTiO-induced prostatic and testicular injury and the corresponding reproductive-related aberrations via redox regulatory, anti-inflammatory and anti-apoptotic mechanisms, promoting steroidogenesis and spermatogenesis, and improving sperm count and morphology.
本研究调查了短期经口暴露于纳米二氧化钛（nTiO）对Wistar大鼠前列腺和睾丸的影响以及相关的生殖系统改变。该研究还评估了天然黄酮类化合物桑色素对nTiO诱导的异常变化的潜在改善作用。经口给予nTiO（50mg/kg/天，持续1、2和3周）会增加睾丸γ-谷氨酰转移酶（γ-GT）活性，降低睾丸类固醇生成急性调节蛋白（StAR）和c-kit基因表达、血清睾酮水平和精子数量。经nTiO处理的大鼠还表现出前列腺和睾丸中谷胱甘肽水平改变、TNF-α水平升高、Fas、Bax和caspase-3基因表达上调、Bcl-2基因表达下调以及前列腺脂质过氧化增强。在2周和3周给药方案后出现精子畸形、睾丸酸性磷酸酶（ACP）活性和丙二醛水平升高、血清前列腺酸性磷酸酶活性、前列腺特异性抗原（PSA）、促性腺激素和雌二醇水平升高。桑色素（经口给予30mg/kg/天，持续5周）减轻了nTiO诱导的前列腺和睾丸损伤，表现为血清PSA水平降低、睾丸γ-GT和ACP活性以及TNF-α水平降低，同时阻碍了内源性和外源性凋亡途径。此外，桑色素减轻了前列腺脂质过氧化，提高了前列腺谷胱甘肽水平，并缓解了睾丸还原应激。此外，桑色素增加了睾丸StAR和c-kit mRNA表达，提高了精子数量，减少了精子畸形，并改善了激素水平的改变。组织病理学评估支持了生化结果。总之，桑色素可通过氧化还原调节、抗炎和抗凋亡机制改善nTiO诱导的前列腺和睾丸损伤以及相应的生殖系统相关异常，促进类固醇生成和精子发生，并改善精子数量和形态。
