ABSTRACT

This study aimed to investigate the relationship between endogenous antioxidant system, 8-hydroxydeoxyguanosine adduct (8-OHdG) repair, and apoptosis in mice treated with chromium(VI) alone and in the presence of the antigenotoxic compound (-)-epigallocatechin-3-gallate (EGCG). Groups of 5 Hsd:ICR male mice were divided and treated as follows: (1) control, vehicle only; (2) EGCG, 8.5 mg/kg by gavage alone; (3) CrO₃, 20 mg/kg intraperitoneally alone; and (4) EGCG combined with CrO₃, EGCG was administered 4 hr prior to CrO₃. Peripheral blood parameters were analyzed before treatment administration (time 0), and 48 hr after exposure. The administration of EGCG increased 8-OHdG levels and superoxide dismutase (SOD) activity. Treatment with CrO₃ increased number of micronucleus (MN) presence, elevated apoptotic/necrotic cells frequencies, decreased 8-OHdG levels, diminished total antioxidant capacity (TAC), increased glutathione (GSH) total levels, and lowered SOD activity. Administration of EGCG prior to treatment with CrO₃ resulted in lower concentrations of MN, reduced apoptotic and necrotic cell number, and restored TAC and SOD activity to control levels. It is conceivable that the dose of EGCG plays an important role in the genotoxic damage protection pathways. Thus, this study confirms the action of EGCG as an antigenotoxic agent against chromium(VI)-induced oxidative insults and demonstrates potential protective pathways for EGCG actions to counteract genotoxic damage induced by this metal.

摘要

本研究旨在研究内源性抗氧化系统、8-羟基脱氧鸟苷加合物 (8-OHdG) 修复与单独使用铬 (VI) 和存在反基因毒性化合物 (-)-epigallocatechin-3- 处理的小鼠细胞凋亡之间的关系。没食子酸酯（EGCG）。将 5 只 Hsd:ICR 雄性小鼠分成几组并进行如下处理：(1) 对照，仅载体；(2) EGCG，8.5 mg/kg 单独灌胃；(3) CrO ₃ , 20 mg/kg 单独腹腔注射；(4)EGCG联合CrO ₃，EGCG在CrO ₃前4小时给药。在治疗给药前（时间 0）和暴露后 48 小时分析外周血参数。EGCG 的给药增加了 8-OHdG 水平和超氧化物歧化酶 (SOD) 活性。CrO ₃处理微核 (MN) 数量增加、凋亡/坏死细胞频率升高、8-OHdG 水平降低、总抗氧化能力 (TAC) 降低、谷胱甘肽 (GSH) 总水平增加和 SOD 活性降低。在用 CrO ₃处理之前施用 EGCG导致较低浓度的 MN，减少凋亡和坏死细胞数量，并将 TAC 和 SOD 活性恢复到控制水平。可以想象，EGCG的剂量在基因毒性损伤保护途径中起重要作用。因此，本研究证实了 EGCG 作为抗铬 (VI) 诱导的氧化损伤的抗原毒性剂的作用，并证明了 EGCG 作用的潜在保护途径，以抵消由该金属诱导的基因毒性损伤。