母亲的镉(Cd)暴露会导致新生儿的呼吸问题,但确切的毒性机制尚未完全了解。镉暴露大鼠维生素D缺乏与组织中镉积累增加有关。寻找一种对身体至关重要的具有成本效益的药物,同时还可以减少中毒的影响,这对于治疗中毒至关重要。探讨镉致肺毒性的机制,我们研究了怀孕前雌性大鼠长时间暴露Cd对新生儿肺部健康的影响,关注血清TNF-α水平,肺P53,Foxo1mRNA,和肺VEGF,和BMP-4蛋白水平。将50只大鼠分为对照组,Cd,Cd+维生素D,Cd+Mg,和Cd+维生素D+Mg组。Cd暴露导致血清TNF-α水平升高,P53mRNA水平显着升高。此外,出血的发生,炎性细胞浸润,用维生素DMg治疗后,肺泡壁的增厚减少。虽然Cd没有影响新生儿的体重,它确实损害了他们的肺功能。这些发现表明Cd诱导的P53基因表达的增加可以通过维生素D和Mg来缓解。随着VEGF和BMP-4蛋白和Foxo1基因表达的升高。研究表明,环境毒素有时会伤害分子和蛋白质,导致关键胎儿组织受损。然而,这些问题可以通过基本补充剂来缓解。结构摘要:Cd在许多生物和分子实体的不稳定行为中的作用越来越大,特别是胎儿肺组织的发育,研究Cd暴露对孕妇和胎儿器官发育可能产生的不利影响,本能分子事件发生的地方。鼓励研究人员创造新的方面的药物,以减少临床症状,提高由于接触金属毒素的生活质量,特别是在工业化国家。本研究旨在评估由母体Cd中毒引起的胎儿肺的组织病理学和分子修饰,并评估维生素D和Mg单独以及与胎儿肺发育异常联合的可能改善作用。其次是母体毒素诱导,可以推广到人类。50只雌性Wistar大鼠从伊朗巴斯德研究所购买。为了诱导模型,在交配前28天(一周内注射后5天),以2mg/kg体重的剂量向雌性大鼠腹膜内注射镉。之后,将雌性大鼠随机分为IV型聚碳酸酯笼,并与健康雄性大鼠交配。通过对阴道斑块的观察证实了妊娠,随后被观察到,并计算了胚胎形成的天数。随后,怀孕的大鼠被分配到以下组,并接受PBS,维生素D,Mg,或维生素D+Mg。在9天治疗期结束时(怀孕第6天至第14天),新生儿是阴道出生的,记录他们的体重和死亡率。评估各组新生儿匀浆化肺左叶和右叶的P53和Foxo1基因表达水平。通过ELISA在从新生儿收集的血清中检测到TNF-α。将分离的左右肺组织在放射免疫沉淀测定(RIPA)缓冲液中进行匀浆,并收集上相,通过Lowry法测定总蛋白含量以及VEGF和BMP-4蛋白水平。将从新生大鼠获得的肺样品固定在10%福尔马林溶液中用于组织处理。将固定的样品包埋在石蜡中,并制备连续的石蜡切片用于苏木精和伊红染色。这项研究是首次研究母体Cd暴露如何影响胎儿肺发育并评估怀孕期间处方Mg和维生素D的影响。本研究评估了怀孕前4周重复剂量的Cd对接受维生素D和Mg治疗的母亲所生的新生大鼠肺发育的影响。结果显示,P53基因在模型组中过度表达,而Foxo1基因表达下调,对胎儿的肺结构和发育指数产生负面影响。因此,维生素D和Mg的摄入可能通过调节肺部炎症和粘膜分泌来改善Cd引起的肺损伤的各个阶段,同时也对存活后代的数量产生积极影响。
Cadmium (Cd) exposure in mothers can cause respiratory issues in newborns, but the exact toxicity mechanisms are not fully understood. Vitamin D deficiency in Cd-exposed rats is associated with increased cadmium accumulation in tissues. Finding a cost-effective medication that is vital for the body while also reducing the effects of poisoning is crucial in treating poisonings. To investigate the mechanisms of Cd-induced lung toxicity, we examined the impact of prolonged Cd exposure in female rats before pregnancy on newborn lung health, focusing on sera TNF-α level, lung P53, Foxo1 mRNA, and lung VEGF, and BMP-4 protein level. A total of 50 rats were divided into control, Cd, Cd+Vitamin D, Cd+Mg, and Cd + Vitamin D+Mg groups. Cd exposure resulted in higher serum TNF-α levels and a significant rise in P53 mRNA levels. Additionally, the occurrence of hemorrhage, inflammatory cell infiltration, and thickening of alveolar walls decreased following treatment with vitamin D + Mg. Although Cd did not affect the newborns\' body weight, it did impair their lung function. These findings suggest that the Cd-induced increase in the P53 gene expression could be alleviated by vitamin D and Mg, along with the elevation of VEGF and BMP-4 proteins and Foxo1 gene expression. The study revealed that environmental toxins can sometimes harm molecules and proteins, leading to damage in critical fetal tissues. However, these issues can be mitigated through essential supplements. STRUCTURED ABSTRACT: The increasing role of Cd in the erratic behavior of numerous biological and molecular entities, notably the development of fetal lung tissue, has made it beneficial to investigate the possible adverse effects of Cd exposure in pregnant mothers and fetal organ development, where instinctive molecular events occur. Researchers are encouraged to create new aspects of medications to reduce clinical symptoms and improve the quality of life due to exposure to metal toxins, particularly in industrialized countries. The present study aimed to evaluate histopathological and molecular modifications of fetal lungs caused by maternal Cd toxicosis and evaluate the possible ameliorating effects of vitamin D and Mg alone and in combination with fetal lung developmental abnormalities, followed by maternal toxin induction, which can be generalized to humans. Fifty female Wistar rats were purchased from the Pasteur Institute of Iran. To induce the model, cadmium at a dose of 2 mg/kg body weight was injected intraperitoneally into the female rats over 28 days before mating (5 days after injection in a week). Afterward, the female rats were randomly divided into type IV polycarbonate cages and mated with healthy male rats. The pregnancy was confirmed by observation of the vaginal plaque, which was subsequently observed, and the number of days of embryo formation was calculated. Subsequently, the pregnant rats were assigned to the following groups and received PBS, vitamin D, Mg, or vitamin D + Mg. At the end of the nine-day treatment period (the 6th day of pregnancy to the 14th day), the neonates were born vaginally, and their body weight and mortality were recorded. The P53 and Foxo1 gene expression levels in the left and right lobes of the homogenized lungs of the newborns in each group were assessed. TNF-alpha was detected in the sera collected from the newborns by ELISA. The isolated left and right lung tissues were homogenized in radioimmunoprecipitation assay (RIPA) buffer and the superior phase was collected to determine the total protein content by Lowry\'s method and VEGF and BMP-4 protein levels. The obtained lung samples from newborn rats were fixed in a 10% formalin solution for tissue processing. The fixed samples were embedded in paraffin, and serial paraffin sections were prepared for hematoxylin and eosin staining. This study is the first to examine how maternal Cd exposure affects fetal lung development and to estimate the impact of prescribing Mg and vitamin D during pregnancy. The present study assessed the effects of a repeated dose of Cd for 4 weeks before pregnancy on the lung development of newborn rats born to mothers treated with vitamin D and Mg. The results showed that the P53 gene was overexpressed in the model group, while Foxo1 gene expression was downregulated, negatively impacting the lung structure and developmental indices of the fetuses. Therefore, the intake of vitamin D and Mg may contribute to improving the various stages of Cd-induced lung injury by modulating lung inflammation and mucosal secretion while also positively influencing the number of surviving offspring.