Abstract：
2-Methyl-4-nitroaniline (MNA), an intermediate in the synthesis of azo dyes, is widely distributed in various environmental media and organisms. Although there is speculation regarding MNA\'s potential to be hepatotoxic, the underlying mechanisms of its hepatotoxicity and its definitive diagnostic process remain largely unexplored. In this research. In the present study, we initially predicted the toxicity and possible toxic effect pathways of MNA using ProTox-II, and found that MNA binds to the PPARγ receptor (binding energy －6.118 kcal/mol) with a potential PPARγ agonist effect. Subsequently, in vivo exposure evaluation was conducted on Wistar rats to assess the impact of MNA after a 90-day exposure period, by detecting serum biochemical indexes, hematological indexes, urinary indexes, inflammatory factors, liver histopathological observations and liver tissue PPARγ mRNA expression. The results showed that MNA causes liver function abnormalities, liver histopathological changes and inflammatory response, along with a pronounced increase in PPARγ mRNA levels. This study suggests that the hepatotoxic mechanism of MNA may be related to its possible upregulation of PPARγ expression, increased liver dysfunction and inflammatory responses. Based on these results, the benchmark dose lower limit (BMDL) of 1.503 mg/kg for male Wistar rats was also established, providing a vital benchmark for determining the safety threshold of MNA. Our data highlight the hepatotoxic mechanism of MNA and contribute to a better understanding of its potential etiological diagnosis.
摘要：
2-甲基-4-硝基苯胺(MNA),偶氮染料合成的中间体，广泛分布于各种环境介质和生物体中。虽然有关于MNA可能具有肝毒性的猜测，肝毒性的潜在机制及其明确的诊断过程仍未被研究.在这项研究中。在本研究中,我们最初使用ProTox-II预测了MNA的毒性和可能的毒性作用途径，并发现MNA与PPARγ受体（结合能-6.118kcal/mol）结合，具有潜在的PPARγ激动剂作用。随后，对Wistar大鼠进行体内暴露评估，以评估90天暴露期后MNA的影响，通过检测血清生化指标，血液学指标,尿指标,炎症因子，肝组织病理学观察及肝组织PPARγmRNA表达。结果显示MNA导致肝功能异常,肝脏组织病理学改变和炎症反应，随着PPARγmRNA水平的显着增加。本研究提示MNA的肝毒性机制可能与其上调PPARγ表达有关,增加肝功能障碍和炎症反应。基于这些结果,还建立了雄性Wistar大鼠的基准剂量下限（BMDL）为1.503mg/kg，为确定MNA的安全阈值提供了重要的基准。我们的数据突出了MNA的肝毒性机制，并有助于更好地了解其潜在的病因诊断。
