Protective effects of zinc L-carnosine against hydrogen peroxide-induced DNA damage and micronucleus formation in CCD-18co human colon fibroblast cells

Abstract

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.

Keywords:

• Antioxidant
• DNA damage
• micronucleus
• metallothionein
• zinc L-carnosine

Acknowledgments

The authors would like to acknowledge the Centre for Research and Instrumentation Management (CRIM), UKM, for providing the gel photo documentation system and flow cytometer facility.

Disclosure statement

The authors report no conflict of interest.

Additional information

Funding

This work was supported by the Ministry of Higher Education Malaysia under Grant FRGS/1/2013/SKK03/UKM/03/1 and Universiti Kebangsaan Malaysia under Grant DIP-2012-024.