Abstract：
There are various substances that can disrupt the homeostatic mechanisms of the body, defined as endocrine-disrupting chemicals (EDCs). The persistent nature of microplastics (MPs) is a cause for concern due to their ability to accumulate in food chains and widespread use, making their toxic effects particularly alarming. The potential of MPs for disrupting the endocrine system was observed in multiple tissues. Moreover, the adrenal gland is known to be extremely sensitive to EDCs, while with the effect of MPs on the adrenal gland has not previously been studied. This study aimed to highlight the potential polyethylene microplastics (PE-MPs) induced adreno-toxic effects rather than exploring the implicated mechanisms and concluding if melatonin (Mel) can afford protection against PE-MPs induced adreno-toxicity. To fulfill the goal, six groups of rats were used; control, Mel, PE-MPs (3.75 mg/kg), PE-MPs (15 mg/kg), PE-MPs (3.75 mg/kg) +Mel, and PE-MPs (15 mg/kg) +Mel. PE-MPs induced toxic changes in the adrenal cortex, which was evident by increased adrenal weight, histopathological examination, and ultrastructural changes detected by electron microscope. A reduction in serum cortisol and an increase in serum adrenocorticotropic hormone resulted from the adreno-toxic effects of PE-MPs. Mechanisms may include the reduction of steroidogenesis-related genes, as PE-MPs drastically reduce mRNA levels of StAR, Nr0b1, Cyp11A1, as well as Cyp11B1. Also, oxidative stress that results from PE-MPs is associated with higher rates of lipid peroxidation and decreased superoxide dismutase and glutathione. PE-MPs inflammatory effect was illustrated by elevated expression of IL-1β and NF-ķB, detected by immunohistochemical staining, in addition to increased expression of caspase-3 and mRNA of Bax, markers of proapoptotic activity. The impacts of PE-MPs were relatively dose-related, with the higher dose showing more significant toxicity than the lower one. Mel treatment was associated with a substantial amelioration of PE-MPs-induced toxic changes. Collectively, this study fills the knowledge gap about the MPs-induced adrenal cortex and elucidates various related toxic mechanisms. It also supports Mel\'s potential protective activity through antioxidant, anti-inflammatory, anti-apoptotic, and gene transcription regulatory effects.
摘要：
有各种物质可以破坏身体的稳态机制，定义为内分泌干扰化学物质（EDCs）。由于微塑料（MPs）在食物链中积累和广泛使用的能力，其持久性是令人担忧的。使它们的毒性效应尤其令人担忧。在多个组织中观察到MPs破坏内分泌系统的潜力。此外，已知肾上腺对EDC极其敏感,而与MPs对肾上腺的影响以前还没有研究过。这项研究旨在强调潜在的聚乙烯微塑料（PE-MPs）诱导的肾上腺毒性作用，而不是探索相关机制，并得出结论褪黑激素（Mel）是否可以提供对PE-MPs诱导的肾上腺毒性的保护。为了实现目标，使用六组大鼠；对照组，梅尔,PE-MPs（3.75mg/kg），PE-MPs（15mg/kg），PE-MPs（3.75mg/kg）+Mel，和PE-MPs(15mg/kg)+Mel。PE-MPs诱导肾上腺皮质毒性变化，肾上腺重量增加很明显，组织病理学检查,电子显微镜检测到超微结构变化。PE-MPs的肾上腺毒性作用导致血清皮质醇减少和血清促肾上腺皮质激素增加。机制可能包括减少类固醇生成相关基因，随着PE-MPs大幅降低StAR的mRNA水平，Nr0b1，Cyp11A1，以及Cyp11B1。此外，由PE-MPs引起的氧化应激与较高的脂质过氧化率以及降低的超氧化物歧化酶和谷胱甘肽相关。通过IL-1β和NF-κB的表达升高说明PE-MPs的炎症作用。通过免疫组织化学染色检测，除了caspase-3和BaxmRNA的表达增加外，促凋亡活性的标志物。PE-MPs的影响是相对剂量相关的，较高的剂量比较低的剂量显示出更显著的毒性。Mel治疗与PE-MPs引起的毒性变化的实质性改善有关。总的来说，这项研究填补了有关MPs诱导的肾上腺皮质的知识空白，并阐明了各种相关的毒性机制。它还通过抗氧化剂支持梅尔的潜在保护活性，抗炎,抗凋亡，和基因转录调节作用。
