Abstract：
Recent population and animal studies have revealed a correlation between fat content and the severity of benzene-induced hematologic toxicity. However, the precise impact of lipid deposition on benzene-induced hematotoxicity and the underlying mechanisms remain unclear. In this study, we established a mouse model with moderate lipid accumulation by subjecting the mice to an 8-week high-fat diet (45% kcal from fat, HFD), followed by 28-day inhalation of benzene at doses of 0, 1, 10, and 100 ppm. The results showed that benzene exposure caused a dose-dependent reduction of peripheral white blood cell (WBC) counts in both diet groups. Notably, this reduction was less pronounced in the HFD-fed mice, suggesting that moderate lipid accumulation mitigates benzene-related hematotoxicity. To investigate the molecular basis for this effect, we performed bioinformatics analysis of high-throughput transcriptome sequencing data, which revealed that moderate lipid deposition alters mouse metabolism and stress tolerance towards xenobiotics. Consistently, the expression of key metabolic enzymes, such as Cyp2e1 and Gsta1, were upregulated in the HFD-fed mice upon benzene exposure. Furthermore, we utilized a real-time exhaled breath detection technique to monitor exhaled benzene metabolites, and the results indicated that moderate lipid deposition enhanced metabolic activation and increased the elimination of benzene metabolites. Collectively, these findings demonstrate that moderate lipid deposition confers reduced susceptibility to benzene-induced hematotoxicity in mice, at least in part, by accelerating benzene metabolism and clearance.
摘要：
最近的人群和动物研究表明，脂肪含量与苯引起的血液学毒性的严重程度之间存在相关性。然而,脂质沉积对苯诱导的血液毒性的确切影响及其潜在机制尚不清楚.在这项研究中,我们通过对小鼠进行为期8周的高脂饮食（来自脂肪的45％千卡，HFD),然后以0、1、10和100ppm的剂量吸入苯28天。结果表明，苯暴露导致两个饮食组中外周血白细胞（WBC）计数的剂量依赖性减少。值得注意的是,这种减少在HFD喂养的小鼠中不太明显，表明适度的脂质积累减轻了苯相关的血液毒性。为了研究这种效应的分子基础，我们对高通量转录组测序数据进行了生物信息学分析，这表明适度的脂质沉积会改变小鼠的代谢和对外源性物质的应激耐受性。始终如一，关键代谢酶的表达，例如Cyp2e1和Gsta1在苯暴露后在HFD喂养的小鼠中上调。此外，我们利用实时呼气检测技术来监测呼出的苯代谢物，结果表明，适度的脂质沉积增强了代谢活化，增加了苯代谢物的消除。总的来说，这些发现表明，适度的脂质沉积使小鼠对苯诱导的血液毒性的敏感性降低，至少在某种程度上,通过加速苯的代谢和清除。
