Zinc L-carnosine (ZnC) is a chelated compound of zinc and L-carnosine. The present study aims to determine the protective effects of ZnC against hydrogen peroxide (H₂O₂)-induced oxidative stress and genomic damage in CCD-18co human normal colon fibroblast cells. Generally, cells were pretreated with ZnC (0–100 µM) for 24 h before challenged with 20 µM of H₂O₂ for 1 h to induce oxidative damage. Results showed that pretreatment with ZnC was able to reduce the intracellular ROS level in CCD-18co cells after being challenged with H₂O₂. Moreover, pretreatment with ZnC demonstrated protection from H₂O₂-induced DNA strand breaks and micronucleus formation. Our current findings revealed that pretreatment with ZnC could induce the activation of MTF-1 signaling pathway and expression of metallothionein (MT) in a dose-dependent manner. However, ZnC did not have any effects on Nrf2 signaling pathway and the expression of glutathione, superoxide dismutase 1, and glutamate-cysteine ligase catalytic subunit (GCLC). Furthermore, pretreatment with ZnC did not induce the expression of OGG1 and PARP-1 in CCD-18co cells, suggesting that these two DNA repairing enzymes are not related to the genoprotective effects of ZnC. Since the expression of MT has been demonstrated to protect cells from oxidative DNA damage induced by various genotoxic agents, the genoprotective effects of ZnC might be due to the ability of ZnC to induce the expression of MT. In conclusion, ZnC pretreatment was able to protect CCD-18co cells from H₂O₂-induced genomic damage via the activation of the MTF-1 signalling pathway and the induction of MT expression.

锌L-肌肽（ZnC）是锌和L-肌氨酸的螯合化合物。本研究旨在确定ZnC对CCD-18co人正常结肠成纤维细胞中过氧化氢（H ₂ O ₂）诱导的氧化应激和基因组损伤的保护作用。通常，将细胞用ZnC（0–100 µM）预处理24 h，然后用20 µM H ₂ O ₂刺激1 h以诱导氧化损伤。结果显示，ZnC预处理能够在受到H ₂ O ₂攻击后降低CCD-18co细胞的细胞内ROS水平。此外，用ZnC进行预处理可防止H ₂ O ₂-诱导的DNA链断裂和微核形成。我们目前的发现表明，用ZnC进行预处理可以以剂量依赖的方式诱导MTF-1信号通路的激活和金属硫蛋白（MT）的表达。但是，ZnC对Nrf2信号通路和谷胱甘肽，超氧化物歧化酶1和谷氨酸半胱氨酸连接酶催化亚基（GCLC）的表达没有任何影响。此外，用ZnC预处理不会诱导CCD-18co细胞中OGG1和PARP-1的表达，这表明这两种DNA修复酶与ZnC的基因保护作用无关。由于已经证明MT的表达可以保护细胞免受各种遗传毒性剂诱导的DNA氧化损伤，因此ZnC的基因保护作用可能是由于ZnC诱导MT表达的能力所致。₂ O ₂通过激活MTF-1信号通路和诱导MT表达来诱导基因组损伤。