Role of Vitamin D and Other Compounds in the Protection of Skin Cells from UV
Access status:
USyd Access
Type
ThesisThesis type
Doctor of PhilosophyAuthor/s
Tongkao-on, WannitAbstract
My studies have further extended our knowledge about the photoprotective roles of vitamin D-like compounds and another agent, eicosapentaenoic acid. My findings indicate that males compared with females, estrogen receptor (ER) knockout females compared with wild type C57Bl/6 mice ...
See moreMy studies have further extended our knowledge about the photoprotective roles of vitamin D-like compounds and another agent, eicosapentaenoic acid. My findings indicate that males compared with females, estrogen receptor (ER) knockout females compared with wild type C57Bl/6 mice and female mice treated with an ER antagonist compared with vehicle, are less sensitive to the protective effects of topical 1,25-dihydroxyvitamin D3 (1,25(OH)2D), in reducing DNA damage in UVR-exposed mouse skin and immunosuppression. This study also showed that the protective effects of 1,25(OH)2D were not only seen in Skh:hr1 mice. I confirmed the potential anti-photocarcinogenic role of 20-hydroxyvitamin D3 (20OHD), a vitamin D metabolite which does not depend on 1α-hydroxylation for production. 20OHD reduced UV-induced DNA damage and immune suppression in mice in short-term studies. I then examined an alternative agent, eicosapentaenoic acid (EPA), an omega-3 fatty acid known for its anti-inflammatory activity, and found that long-term use of topical EPA in mice could reduce, to some extent, the severity of photocarcinogenesis. These results were consistent with the evidence I have presented of significant protection by EPA in short-term studies. Finally, the anti-photocarcinogenic role of tetrahydrocurcumin (THC), an anti-oxidative substance which is derived from curcumin, was investigated. THC is proposed to bind to an alternative site on the vitamin D receptor and may act as a vitamin D-like compound, able to stimulate the vitamin D signalling and to mediate photoprotection. I found that THC has photoprotective properties like 1,25(OH)2D at nanomolar concentrations. Protective effects of THC were demonstrated against acute UV-induced skin damage and were also evident in a chronic study. THC substantially reduced the number of squamous cell carcinomas in mice after chronic UV exposure. Overall, the work described in this thesis has translational potential for prevention of skin cancer.
See less
See moreMy studies have further extended our knowledge about the photoprotective roles of vitamin D-like compounds and another agent, eicosapentaenoic acid. My findings indicate that males compared with females, estrogen receptor (ER) knockout females compared with wild type C57Bl/6 mice and female mice treated with an ER antagonist compared with vehicle, are less sensitive to the protective effects of topical 1,25-dihydroxyvitamin D3 (1,25(OH)2D), in reducing DNA damage in UVR-exposed mouse skin and immunosuppression. This study also showed that the protective effects of 1,25(OH)2D were not only seen in Skh:hr1 mice. I confirmed the potential anti-photocarcinogenic role of 20-hydroxyvitamin D3 (20OHD), a vitamin D metabolite which does not depend on 1α-hydroxylation for production. 20OHD reduced UV-induced DNA damage and immune suppression in mice in short-term studies. I then examined an alternative agent, eicosapentaenoic acid (EPA), an omega-3 fatty acid known for its anti-inflammatory activity, and found that long-term use of topical EPA in mice could reduce, to some extent, the severity of photocarcinogenesis. These results were consistent with the evidence I have presented of significant protection by EPA in short-term studies. Finally, the anti-photocarcinogenic role of tetrahydrocurcumin (THC), an anti-oxidative substance which is derived from curcumin, was investigated. THC is proposed to bind to an alternative site on the vitamin D receptor and may act as a vitamin D-like compound, able to stimulate the vitamin D signalling and to mediate photoprotection. I found that THC has photoprotective properties like 1,25(OH)2D at nanomolar concentrations. Protective effects of THC were demonstrated against acute UV-induced skin damage and were also evident in a chronic study. THC substantially reduced the number of squamous cell carcinomas in mice after chronic UV exposure. Overall, the work described in this thesis has translational potential for prevention of skin cancer.
See less
Date
2015-06-29Licence
The author retains copyright of this thesis. It may only be used for the purposes of research and study. It must not be used for any other purposes and may not be transmitted or shared with others without prior permission.Faculty/School
Sydney Medical SchoolDepartment, Discipline or Centre
Discipline of PhysiologyAwarding institution
The University of SydneyShare