Protective Effect of Indole-3-Pyruvate against Ultraviolet B-Induced Damage to Cultured HaCaT Keratinocytes and the Skin of Hairless MiceReport as inadecuate




Protective Effect of Indole-3-Pyruvate against Ultraviolet B-Induced Damage to Cultured HaCaT Keratinocytes and the Skin of Hairless Mice - Download this document for free, or read online. Document in PDF available to download.

Previous investigations demonstrated that pyruvate protects human keratinocytes against cell damage stemming from exposure to ultraviolet B UVB radiation. This study endeavoured to elucidate the protective capacity of aromatic pyruvates e.g., phenylpyruvate PPyr, 4-hydroxyphenylpyruvate HPPyr, and indole-3-pyruvate IPyr against UVB-induced injury to skin cells, both in vitro and in vivo. Cultured human HaCaT keratinocytes were irradiated with UVB light 60 mJ-cm2 and maintained with or without test compounds 1–25 mM. In addition, the dorsal skin of hairless mice HR-1 was treated with test compounds 100 µmol and exposed to UVB light 1 J-cm2 for two times. The ability of the test compounds to ameliorate UVB-induced cytotoxicity and inflammation was then assessed. Aromatic pyruvates reduced cytotoxicity in UVB-irradiated HaCaT keratinocytes, and also diminished the expression of interleukin 1β IL-1β and interleukin 6 IL-6. IPyr was more efficacious than either PPyr or HPPyr. Furthermore, only IPyr inhibited cyclooxygenase-2 Cox-2 expression at both the mRNA and the protein level in UVB-treated keratinocytes. Topical application of IPyr to the dorsal skin of hairless mice reduced the severity of UVB-induced skin lesions, the augmentation of dermal thickness, and transepithelial water loss. Overproduction of IL-1β and IL-6 in response to UVB radiation was also suppressed in vivo by the topical administration of IPyr. These data strongly suggest that IPyr might find utility as a UVB-blocking reagent in therapeutic strategies to lessen UVB-induced inflammatory skin damage.



Author: Reiji Aoki, Ayako Aoki-Yoshida, Chise Suzuki, Yoshiharu Takayama

Source: http://plos.srce.hr/



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