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Zinc l-Carnosine Protects CCD-18co Cells from l-Buthionine Sulfoximine–Induced Oxidative Stress via the Induction of Metallothionein and Superoxide Dismutase 1 Expression

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Abstract

Zinc l-carnosine (ZnC) is the chelate form of zinc and l-carnosine and is one of the zinc supplements available in the market. This study aims to determine the protective effects of ZnC against l-buthionine sulfoximine (BSO)–induced oxidative stress in CCD-18co human normal colon fibroblast cell line. CCD-18co cells were pretreated with ZnC (0–100 μM) for 24 h before the induction of oxidative stress by BSO (1 mM) for another 24 h. Results from this present study demonstrated that ZnC up to the concentration of 100 μM was not cytotoxic to CCD-18co cells. Induction with BSO significantly increased the intracellular reactive oxygen species (ROS) levels and reduced the intracellular glutathione (GSH) levels in CCD-18co cells. Pretreatment with ZnC was able to attenuate the increment in intracellular ROS level in CCD-18co cells significantly in a concentration-dependent manner. However, ZnC did not have any effects on intracellular GSH levels and Nrf2 activation. Mechanistically, pretreatment with ZnC was able to upregulate the expression of metallothionein (MT) and superoxide dismutase 1 (SOD1) in CCD-18co cells. Results from dual-luciferase reporter gene assay reported that ZnC was able to increase the MRE-mediated relative luciferase activities in a concentration-dependent manner, suggesting that the induction of MT expression by ZnC was due to the activation of MTF-1 signaling pathway. Taken together, our current findings suggest that ZnC can protect CCD-18co cells from BSO-induced oxidative stress via the induction of MT and SOD1 expression.

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Acknowledgments

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

Funding

This study was funded by the Fundamental Research Grant Scheme, Ministry of Education Malaysia (FRGS/1/2013/SKK03/UKM/03/1), and the Universiti Kebangsaan Malaysia (DIP-2012-024).

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Authors and Affiliations

  1. Center for Healthy Ageing & Wellness, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300, Kuala Lumpur, Malaysia

    Theng Choon Ooi & Razinah Sharif

  2. Environmental Health and Industrial Safety Programme, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300, Kuala Lumpur, Malaysia

    Kok Meng Chan

  3. Biocompatibility Laboratory, Centre for Research and Instrumentation, Universiti Kebangsaan Malaysia, 43600, UKM Bangi, Selangor Darul Ehsan, Malaysia

    Razinah Sharif

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  1. Theng Choon Ooi
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Correspondence to Razinah Sharif.

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Ooi, T.C., Chan, K.M. & Sharif, R. Zinc l-Carnosine Protects CCD-18co Cells from l-Buthionine Sulfoximine–Induced Oxidative Stress via the Induction of Metallothionein and Superoxide Dismutase 1 Expression. Biol Trace Elem Res 198, 464–471 (2020). https://doi.org/10.1007/s12011-020-02108-9

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