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Ameliorative mechanism of dietary vitamin d and magnesium on newborn's pulmonary toxicity induced by cadmium. 膳食维生素 d 和镁对镉引起的新生儿肺中毒的改善机制
Paria Amanpour, Zohre Eftekhari, Akram Eidi, Parvin Khodarahmi

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 vitam

母亲接触镉(Cd)会导致新生儿呼吸道问题,但确切的毒性机制尚不完全清楚。暴露于镉的大鼠缺乏维生素 D 与镉在组织中的蓄积增加有关。找到一种既对身体至关重要,又能减轻中毒影响的经济有效的药物,对于治疗中毒至关重要。为了探究镉诱导肺毒性的机制,我们研究了雌性大鼠孕前长期接触镉对新生儿肺健康的影响,重点关注血清TNF-α水平、肺P53、Foxo1 mRNA、肺血管内皮生长因子和BMP-4蛋白水平。50只大鼠被分为对照组、镉组、镉+维生素D组、镉+镁组和镉+维生素D+镁组。镉暴露导致血清 TNF-α 水平升高,P53 mRNA 水平显著升高。此外,使用维生素 D+Mg 治疗后,出血、炎症细胞浸润和肺泡壁增厚的发生率均有所下降。虽然镉不会影响新生儿的体重,但会损害他们的肺功能。这些研究结果表明,维生素 D 和镁可以缓解镉引起的 P53 基因表达的增加,以及血管内皮生长因子和 BMP-4 蛋白和 Foxo1 基因表达的升高。研究显示,环境毒素有时会伤害分子和蛋白质,导致胎儿关键组织受损。不过,这些问题可以通过必要的补充剂来缓解。结构式摘要:镉在许多生物和分子实体的不稳定行为(特别是胎儿肺组织的发育)中的作用越来越大,这使得研究镉暴露对怀孕母亲和胎儿器官发育可能产生的不利影响变得有益,因为在胎儿器官发育过程中会发生本能的分子事件。人们鼓励研究人员开发新的药物,以减少因接触金属毒素而引起的临床症状,提高生活质量,尤其是在工业化国家。本研究旨在评估母体镉中毒对胎儿肺部造成的组织病理学和分子改变,并评估在母体毒素诱导后,维生素 D 和镁单独或联合使用对胎儿肺部发育异常可能产生的改善作用,从而推广到人类。50 只雌性 Wistar 大鼠购自伊朗巴斯德研究所。为了诱导该模型,在交配前 28 天(一周内注射 5 天),向雌性大鼠腹腔注射 2 毫克/千克体重的镉。然后,将雌性大鼠随机分入 IV 型聚碳酸酯笼中,与健康雄性大鼠交配。随后通过观察阴道斑块确认怀孕,并计算胚胎形成的天数。随后,怀孕大鼠被分配到以下组别,分别接受 PBS、维生素 D、Mg 或维生素 D + Mg 的治疗。在为期九天的治疗期(怀孕第 6 天至第 14 天)结束时,新生大鼠经阴道出生,并记录其体重和死亡率。评估各组新生儿匀浆肺左叶和右叶的 P53 和 Foxo1 基因表达水平。用酶联免疫吸附法检测新生儿血清中的 TNF-α。用放射免疫沉淀法(RIPA)缓冲液匀浆分离左肺和右肺组织,收集上相,用 Lowry 法测定总蛋白含量以及 VEGF 和 BMP-4 蛋白水平。将获得的新生大鼠肺部样本固定在 10% 福尔马林溶液中进行组织处理。将固定好的样本包埋在石蜡中,制备连续石蜡切片进行苏木精和伊红染色。这项研究首次探讨了母体镉暴露如何影响胎儿肺部发育,并估算了孕期服用镁和维生素 D 的影响。本研究评估了妊娠前4周重复剂量的镉对服用维生素D和镁的母亲所生新生大鼠肺部发育的影响。结果显示,模型组中 P53 基因表达过高,而 Foxo1 基因表达下调,对胎儿的肺部结构和发育指标产生了负面影响。因此,维生素 D 和镁的摄入可通过调节肺部炎症和粘膜分泌来改善镉诱导的肺损伤的各个阶段,同时对后代存活数量产生积极影响。
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Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)
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