Đurašević Siniša, Pejić Snežana, Grigorov Ilijana, Nikolić Gorana, Mitić-Ćulafić Dragana, Dragićević Milan, Đorđević Jelena, Todorović Vukotić Nevena, Đorđević Neda, Todorović Ana, Drakulić Dunja, Veljković Filip, Pajović Snežana B, Todorović Zoran
Faculty of Biology, University of Belgrade, Studentski Trg 16, 11000 Belgrade, Serbia.
"Vinča" Institute of Nuclear Sciences, National Institute of the Republic of Serbia, University of Belgrade, Mike Petrovića Alasa 12-14, 11000 Belgrade, Serbia.
Antioxidants (Basel). 2021 Jun 4;10(6):911. doi: 10.3390/antiox10060911.
Thioacetamide (TAA) is widely used to study liver toxicity accompanied by oxidative stress, inflammation, cell necrosis, fibrosis, cholestasis, and hepatocellular carcinoma. As an efficient free radical's scavenger, C60 fullerene is considered a potential liver-protective agent in chemically-induced liver injury. In the present work, we examined the hepatoprotective effects of two C60 doses dissolved in virgin olive oil against TAA-induced hepatotoxicity in rats. We showed that TAA-induced increase in liver oxidative stress, judged by the changes in the activities of SOD, CAT, GPx, GR, GST, the content of GSH and 4-HNE, and expression of HO-1, MnSOD, and CuZnSOD, was more effectively ameliorated with a lower C60 dose. Improvement in liver antioxidative status caused by C60 was accompanied by a decrease in liver HMGB1 expression and an increase in nuclear Nrf2/NF-κB p65 ratio, suggesting a reduction in inflammation, necrosis and fibrosis. These results were in accordance with liver histology analysis, liver comet assay, and changes in serum levels of ALT, AST, and AP. The changes observed in gut microbiome support detrimental effects of TAA and hepatoprotective effects of low C60 dose. Less protective effects of a higher C60 dose could be a consequence of its enhanced aggregation and related pro-oxidant role.
硫代乙酰胺（TAA）被广泛用于研究伴有氧化应激、炎症、细胞坏死、纤维化、胆汁淤积和肝细胞癌的肝毒性。作为一种高效的自由基清除剂，C60富勒烯被认为是化学诱导肝损伤中一种潜在的肝脏保护剂。在本研究中，我们检测了溶解在初榨橄榄油中的两种C60剂量对TAA诱导的大鼠肝毒性的肝脏保护作用。我们发现，通过超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GPx）、谷胱甘肽还原酶（GR）、谷胱甘肽S-转移酶（GST）的活性变化、谷胱甘肽（GSH）和4-羟基壬烯醛（4-HNE）的含量以及血红素加氧酶-1（HO-1）、锰超氧化物歧化酶（MnSOD）和铜锌超氧化物歧化酶（CuZnSOD）的表达来判断，TAA诱导的肝脏氧化应激增加，用较低剂量的C60能更有效地改善。C60引起的肝脏抗氧化状态改善伴随着肝脏高迁移率族蛋白B1（HMGB1）表达的降低和核内Nrf2/NF-κB p65比值的增加，表明炎症、坏死和纤维化减少。这些结果与肝脏组织学分析、肝脏彗星试验以及血清谷丙转氨酶（ALT）、谷草转氨酶（AST）和碱性磷酸酶（AP）水平的变化一致。在肠道微生物群中观察到的变化支持了TAA的有害作用和低剂量C60的肝脏保护作用。较高剂量的C60保护作用较小可能是其聚集增强和相关促氧化作用导致的。
