Department of Pharmacology & Toxicology, Faculty of Pharmacy, MTI University, Cairo, Egypt.
Department of Pharmacology & Toxicology, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt.
Toxicology. 2021 Jun 15;457:152808. doi: 10.1016/j.tox.2021.152808. Epub 2021 May 15.
We have addressed in the current study the potential of L-carnitine (LC) to extenuate the reproductive toxic insults of carbendazim (CBZ) in male rats, and the molecular mechanisms whereby carnitine would modify the spermatogenic and steroidogenic derangements invoked by the endocrine disruptor. Herein, animals received daily doses of carbendazim (100 mg/kg) by gavage for 8 weeks. Another CBZ-challenged group was co-supplemented with LC (500 mg/kg, IP) twice weekly for 8 weeks. Sperm quantity and quality (morphology, motility and viability), serum testosterone and gonadotropins, and thyroid hormone levels were assessed. Serum tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10) concentrations were determined by ELISA. Oxidant/antioxidant status in rat testis was investigated via measuring testicular contents of malondialdehyde (MDA) and reduced glutathione (GSH), as well as the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx). Immunohistochemical localizations of the junctional protein; occludin, and inflammatory markers; inducible nitric oxide synthase (iNOS) and nuclear factor kappa beta (NF-κB) were further analyzed. A host of transduction genes that regulate spermatogenic and steroidogenic pathways, and their encoded proteins namely, Steroidogenic Acute Regulatory Protein (StAR), Fatty acid binding protein 9 (FABP9) and P38-mitogen activated protein kinase (P38-MAPK) were assessed by real time quantitative (RT-qPCR) and Western blot. LC improved rat spermiogram, testicular histological alterations and endocrine perturbances, and modulated genes' expressions and their respective proteins. In conclusion, LC effects appear to reside for the most part on its endocrine-preserving, anti-oxidant and anti-inflammatory properties through a myriad of interlaced signal transductions that ultimately recapitulated its beneficial effects on spermatogenesis and steroidogenesis.
我们在当前的研究中探讨了左旋肉碱（LC）减轻咪鲜胺（CBZ）对雄性大鼠生殖毒性损伤的潜力，以及肉碱通过何种分子机制来调节内分泌干扰物引起的精子发生和类固醇生成紊乱。在此，动物通过灌胃每天接受 100mg/kg 的咪鲜胺 8 周。另一组 CBZ 处理的动物每周两次接受 500mg/kg 的 LC 腹腔注射共 8 周。评估精子数量和质量（形态、活力和活力）、血清睾酮和促性腺激素以及甲状腺激素水平。通过 ELISA 测定血清肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和白细胞介素-10（IL-10）的浓度。通过测量睾丸丙二醛（MDA）和还原型谷胱甘肽（GSH）的含量以及超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GPx）的活性来研究大鼠睾丸的氧化应激/抗氧化状态。进一步分析连接蛋白；occludin 和炎症标志物；诱导型一氧化氮合酶（iNOS）和核因子 kappa beta（NF-κB）的免疫组织化学定位。通过实时定量（RT-qPCR）和 Western blot 评估调节精子发生和类固醇生成途径的一系列转导基因及其编码蛋白，即类固醇急性调节蛋白（StAR）、脂肪酸结合蛋白 9（FABP9）和 P38-有丝分裂原激活蛋白激酶（P38-MAPK）。LC 改善了大鼠精子图谱、睾丸组织学改变和内分泌紊乱，并调节了基因的表达及其各自的蛋白。总之，LC 的作用似乎主要通过其内分泌保护、抗氧化和抗炎特性来实现，通过一系列相互交织的信号转导，最终再现了其对精子发生和类固醇生成的有益作用。
