Exposure to light at night, pineal gland impairment, and the environmental pollutant trichloroethylene (TCE) have serious implications for health and contribute to illness, including liver cancer. The adverse effect of the association of continuous exposure to light with decreased melatonin levels and TCE-induced toxicity is not disclosed in target organs. This work explored the role of light and pineal impairment in increasing susceptibility to liver toxicity and cancer upon exposure to TCE. Male albino mice were divided into groups as follows: control group (12-h light/12-h dark cycle), constant light (24-h light), pinealectomized (Pnx) mice, sham surgically treated group, TCE-treated groups subjected to two doses (500 and 1000 mg/kg) at two different light regimens, and combination of Pnx and TCE-treated mice kept at a 12-h light/12-h dark cycle. Melatonin levels were significantly decreased in both Pnx mice and TCE-treated animals at both light regimens. Aspartate transaminase, alanine aminotransferase, activities, and serum bilirubin levels were significantly elevated, whereas albumin levels were markedly decreased in Pnx mice, TCE-treated mice, and the combination group. Histopathological investigations reflected changes in liver function parameters indicating liver injury and induction of cancer. These effects were accompanied by significant increase of the liver cancer biomarker alpha-fetoprotein and the expression of the metastatic markers CD44, TGFβ-1, and VEGF, along with increased oxidative stress indicators and inflammatory cytokines (IL-6, IL-1β, and TNF-α) in both Pnx and TCE-treated mice and the combination group at both light regimens. Taken together, our findings indicated that low melatonin levels, exposure to constant light, and the combination of both factors increases susceptibility to the toxic and carcinogenic effects of TCE on the liver.

夜间暴露在光线下、松果体受损和环境污染物三氯乙烯 (TCE) 对健康有严重影响，并导致包括肝癌在内的疾病。靶器官中未公开持续暴露于光与褪黑激素水平降低和 TCE 诱导的毒性相关的不利影响。这项工作探讨了光和松果体损伤在增加接触 TCE 后对肝毒性和癌症的易感性中的作用。雄性白化病小鼠分组如下：对照组（12 小时光照/12 小时黑暗循环）、恒定光照（24 小时光照）、松果体切除（Pnx）小鼠、假手术治疗组、TCE 治疗组以两种不同的光照方案进行两次剂量（500 和 1000 mg/kg），Pnx 和 TCE 处理的小鼠的组合保持在 12 小时光照/12 小时黑暗循环。在两种光照方案下，Pnx 小鼠和 TCE 治疗动物的褪黑激素水平均显着降低。天冬氨酸转氨酶、丙氨酸转氨酶、活性和血清胆红素水平显着升高，而 Pnx 小鼠、TCE 治疗小鼠和联合组的白蛋白水平显着降低。组织病理学研究反映了肝功能参数的变化，表明肝损伤和癌症的诱发。这些影响伴随着肝癌生物标志物甲胎蛋白的显着增加和转移性标志物 CD44、TGFβ-1 和 VEGF 的表达，以及氧化应激指标和炎性细胞因子（IL-6、IL-1β、和 TNF-α) 在 Pnx 和 TCE 治疗的小鼠以及在两种光照方案的组合组中。综上所述，我们的研究结果表明，低褪黑激素水平、暴露于恒定光照以及这两种因素的结合会增加 TCE 对肝脏的毒性和致癌作用的敏感性。