Laboratory of Computational Modeling of Drugs, Higher Medical and Biological School, South Ural State University, 454008 Chelyabinsk, Russia.
Natural Product Drug Discovery Laboratory, Department of Pharmaceutical Sciences, Sam Higginbottom University of Agriculture, Technology and Sciences, Prayagraj 211007, India.
Molecules. 2022 Jul 14;27(14):4499. doi: 10.3390/molecules27144499.
The current study was conducted to exemplify the effect of debelalactone on tissue protection, chronic hepatic inflammation, hepatic protection and oxidative stress induced by diethyl nitrosamine in Wistar rats. Therefore, DEN (200 mg/kg) was used for the induction the hepatocellular carcinoma (HCC) and the level of serum alpha fetoprotein was used for the estimation and confirmation of HCC. The study illustrated that debelalactone (DL) significantly downregulated the hepatic, non-hepatic parameters such as aspartate aminotransferase, alanine aminotransferase, alpha fetoprotein, NO levels, total protein, albumin, blood urea nitrogen, total bilirubin, and direct bilirubin in dose dependent manner, as well as noticeably improving the body weight, of treated animals. The macroscopically observation of DEN-induced rat liver showed the formation of informalities in liver tissue, which was reduced with treatment of DL at dose dependent manner. However, antioxidant markers and inflammatory mediators such as lipid peroxidation, catalase, superoxide dismutase, glutathione peroxidase and transferase, TNF-α, IL-1β, IL-6, and NF-kB restored up to the normal level by DL. The histopathology studies showed that the treated group of animals returned to a normal status. Collectively, it can be concluded that debelalactone mediated chemoprevention in the DEN-induced rats via an increase in the activities of endogenous enzymes and/or inhibition the precancerous cells.
本研究旨在举例说明 debelalactone 对二乙基亚硝胺诱导的 Wistar 大鼠组织保护、慢性肝炎症、肝保护和氧化应激的影响。因此，使用 DEN（200mg/kg）诱导肝细胞癌（HCC），并使用血清甲胎蛋白水平来估计和确认 HCC。研究表明，debelalactone（DL）以剂量依赖的方式显著下调了肝、非肝参数，如天冬氨酸转氨酶、丙氨酸转氨酶、甲胎蛋白、NO 水平、总蛋白、白蛋白、血尿素氮、总胆红素和直接胆红素，以及明显改善了动物的体重。DEN 诱导的大鼠肝脏的宏观观察显示，肝脏组织中出现不规则现象，这种现象随着 DL 的剂量依赖性治疗而减少。然而，抗氧化标记物和炎症介质，如脂质过氧化、过氧化氢酶、超氧化物歧化酶、谷胱甘肽过氧化物酶和转移酶、TNF-α、IL-1β、IL-6 和 NF-kB，通过 DL 恢复到正常水平。组织病理学研究表明，动物的治疗组恢复到正常状态。总之，可以得出结论，debelalactone 通过增加内源性酶的活性和/或抑制癌前细胞，介导 DEN 诱导的大鼠化学预防。
