Cancer Biology Laboratory, Department of Zoology, School of Biological Sciences, Dr. Harisingh Gour Central University, Sagar, India.
Department of Biochemistry, University of Lucknow, Lucknow, India.
J Biochem Mol Toxicol. 2024 Oct;38(10):e23850. doi: 10.1002/jbt.23850.
Hepatocellular carcinoma (HCC) is caused by various factors including toxic substances and xenobiotics. Numerous treatment strategies are used to address toxicity to the liver and HCC, yet their adverse effects are drawbacks. This study aimed to assess the effect of DEN/CCl on morphological changes in the liver, body weight, tumor incidence, and hematological tumor incidence, hematological parameters, hepatic markers, and histopathological analysis in mice following a preventive measure by using β-caryophyllene (BCP). Adult Balb/c mice were administered a single dose of DEN 1-mg/kg body weight and 0.2-mL CCl/kg body weight intraperitoneal twice a week (i.p.) for 22 weeks. BCP was treated in one group of mice at 30-mg/kg body weight, intraperitoneal, for 7 weeks. BCP alone was treated in one group of mice at 300-mg/kg body weight intraperitoneal for 22 weeks. DEN/CCl caused a reduction in mice's body weight, which was significantly attenuated by BCP administration. BCP supplementation attenuated the tumor incidence DEN/CCl (100%) to about 25%. DEN/CCl caused alterations in the hematological parameters, serum total protein albumin globulin, A/G ratio, liver function markers (AST, ALT, ALP, GGT, ACP, and bilirubin), and lipid profile markers that were significantly reinstated by BCP administration. Oxidative stress markers (MDA, SOD, CAT, NO, LDH, and GST) were reduced by DEN/CCl which were significantly increased in BCP-treated groups. The liver histopathology alterations caused by DEN/CCl were amended considerably by BCP treatment. Immunohistochemical studies suggest that AFP, caspase-3, and COX-2 were chronically overexpressed in DEN/CCl-exposed mice, notably attenuated by BCP administration. BCP suppressed tumor incidence by downregulating inflammation and inducing caspase-3-mediated apoptosis. Conclusively, BCP appears to be a potent natural supplement capable of repressing liver inflammation and carcinoma through the mitigation of oxidative stress and inflammation pathways.
肝细胞癌（HCC）是由各种因素引起的，包括有毒物质和外源性物质。有许多治疗策略用于解决肝脏毒性和 HCC，但它们的不良反应是其缺点。本研究旨在评估 DEN/CCl 对肝脏形态变化、体重、肿瘤发生率和血液肿瘤发生率、血液参数、肝标志物和组织病理学分析的影响，以及使用β-石竹烯（BCP）进行预防措施后的小鼠。成年 Balb/c 小鼠单次腹腔注射 DEN 1-mg/kg 体重和 0.2-mL CCl/kg 体重，每周两次（ip）共 22 周。BCP 在一组小鼠中以 30-mg/kg 体重腹腔注射，共 7 周。BCP 单独在一组小鼠中以 300-mg/kg 体重腹腔注射，共 22 周。DEN/CCl 导致小鼠体重减轻，BCP 给药可显著减轻。BCP 补充剂可将 DEN/CCl 引起的肿瘤发生率（100%）降低至约 25%。DEN/CCl 引起的血液参数、血清总蛋白、白蛋白、球蛋白、A/G 比值、肝功能标志物（AST、ALT、ALP、GGT、ACP 和胆红素）和脂质谱标志物的改变，经 BCP 给药后可显著恢复。氧化应激标志物（MDA、SOD、CAT、NO、LDH 和 GST）被 DEN/CCl 降低，而 BCP 处理组显著增加。BCP 治疗可显著改善 DEN/CCl 引起的肝组织病理学改变。免疫组织化学研究表明，AFP、caspase-3 和 COX-2 在 DEN/CCl 暴露的小鼠中持续过表达，BCP 给药可显著减弱。BCP 通过下调炎症和诱导 caspase-3 介导的细胞凋亡来抑制肿瘤发生率。总之，BCP 似乎是一种有效的天然补充剂，能够通过减轻氧化应激和炎症途径来抑制肝脏炎症和癌。
