Photoprotective effects of bucillamine against UV-induced damage in an SKH-1 hairless mouse model.
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.
Anwar
Adil
A
Department of Dermatology, School of Medicine, University of Colorado Health Sciences Center, Anschutz Medical Campus, Aurora, CO, USA.
Gu
Mallikarjuna
M
Brady
Sara
S
Qamar
Lubna
L
Behbakht
Kian
K
Shellman
Yiqun G
YG
Agarwal
Rajesh
R
Norris
David A
DA
Horwitz
Lawrence D
LD
Fujita
Mayumi
M
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D051379:Mice; D008812:Mice, Hairless; D023421:Models, Animal; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014466:Ultraviolet Rays
D000975:Antioxidants; D011837:Radiation-Protective Agents; D016159:Tumor Suppressor Protein p53; D003545:Cysteine; C026535:bucillamine