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Photoprotective Effects of Bucillamine Against UV-induced Damage in an SKH-1 Hairless Mouse Model

Authors

  • Adil Anwar,

    1. Department of Dermatology, School of Medicine, University of Colorado Health Sciences Center, Anschutz Medical Campus, Aurora, CO
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  • Mallikarjuna Gu,

    1. Department of Pharmaceutical Sciences, University of Colorado Health Sciences Center, School of Pharmacy, Denver, CO
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  • Sara Brady,

    1. Department of Dermatology, School of Medicine, University of Colorado Health Sciences Center, Anschutz Medical Campus, Aurora, CO
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  • Lubna Qamar,

    1. Department of Obstetrics and Gynecology, School of Medicine, University of Colorado Health Sciences Center, Anschutz Medical Campus, Aurora, CO
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  • Kian Behbakht,

    1. Department of Obstetrics and Gynecology, School of Medicine, University of Colorado Health Sciences Center, Anschutz Medical Campus, Aurora, CO
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  • Yiqun G. Shellman,

    1. Department of Dermatology, School of Medicine, University of Colorado Health Sciences Center, Anschutz Medical Campus, Aurora, CO
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  • Rajesh Agarwal,

    1. Department of Pharmaceutical Sciences, University of Colorado Health Sciences Center, School of Pharmacy, Denver, CO
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  • David A. Norris,

    1. Department of Dermatology, School of Medicine, University of Colorado Health Sciences Center, Anschutz Medical Campus, Aurora, CO
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  • Lawrence D. Horwitz,

    1. Division of Cardiology, Department of Medicine, University of Colorado Health Sciences Center, Anschutz Medical Campus, Aurora, CO
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  • Mayumi Fujita

    Corresponding author
    1. Department of Dermatology, School of Medicine, University of Colorado Health Sciences Center, Anschutz Medical Campus, Aurora, CO
      *Corresponding author email: mayumi.fujita@uchsc.edu (Mayumi Fujita)
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  • This paper is part of a special issue dedicated to Professor Hasan Mukhtar on the occasion of his 60th birthday.

*Corresponding author email: mayumi.fujita@uchsc.edu (Mayumi Fujita)

Abstract

UVB exposure of skin results in various biologic responses either through direct or indirect damage to DNA and non-DNA cellular targets via the formation of free radicals, reactive oxygen species (ROS) and inflammation. Bucillamine [N-(2-mercapto-2-methylpropionyl)-l-cysteine] is a cysteine-derived compound that can replenish endogenous glutathione due to its two donatable thiol groups, and functions as an antioxidant. In this study, we investigated the effects of bucillamine on UVB-induced photodamage using the SKH-1 hairless mouse model. We have demonstrated that UVB exposure (two consecutive doses, 230 mJ cm−2) on the dorsal skin of SKH-1 mice induced inflammatory responses (edema, erythema, dermal infiltration of leukocytes, dilated blood vessels) and p53 activation as early as 6 h after the last UVB exposure. Bucillamine pretreatment (20 mg kg−1 of body weight, administered subcutaneously) markedly attenuated UVB-mediated inflammatory responses and p53 activation. We have also demonstrated that the stabilization and upregulation of p53 by UVB correlated with phosphorylation of Ser-15 and Ser-20 residues of p53 protein and that bucillamine pretreatment attenuated this effect. We propose that bucillamine has potential to be effective as a photoprotective agent for the management of pathologic conditions elicited by UV exposure.

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