Protective effects of 1,25 dihydroxyvitamin D₃ and its analogs on ultraviolet radiation-induced oxidative stress: a review

ABSTRACT

The active vitamin D compound, 1,25-dihydroxyvitamin D3 (1,25D) is produced in skin cells following exposure to ultraviolet radiation (UV) from the sun. However, there are many harmful effects of UV which include DNA damage caused by direct absorption of UV, as well as that caused indirectly via UV-induced reactive oxygen species (ROS). Interestingly, 1,25D and analogs have been shown to reduce both direct and indirect UV-induced DNA damage in skin cells. This was accompanied by reductions in ROS and in nitric oxide products with 1,25D following UV. Moreover, following acute UV exposure, 1,25D has been demonstrated to increase p53 levels in skin, which would presumably allow for repair of cells with damaged DNA, or apoptosis of cells with irreparably damaged DNA. Previous studies have also shown that p53 reduces intracellular ROS. Furthermore, 1,25D has been shown to induce metallothioneins, which are potent free radical scavengers. In addition to these protective effects, 1,25D has been demonstrated to inhibit stress-activated c-Jun N-terminal kinases following UV exposure, and to increase levels of the stress-induced protein heme oxygenase-1 in a model of oxidative stress. Herein, we discuss the protective effects of 1,25D and analogs in the context of UV, oxidative stress and skin cancer.

KEYWORDS:

• Vitamin D
• 1,25-dihydroxyvitamin D3 (1,25D)
• oxidative stress
• reactive oxygen species (ROS)
• p53
• metallothionein (MT)
• DNA damage
• c-Jun N-terminal kinases (JNK)

Disclosure statement

No potential conflict of interest was reported by the author(s).

Notes on contributors

Shemani Jagoda graduated from The University of Sydney with a Bachelor’s degree in Science, majoring in Immunology. She is currently pursuing a Doctor of Medicine degree, also at the University of Sydney, where she continues to be involved in oncological research particularly concerning the role of perivascular macrophages in the tumour microenvironment.

Dr. Dixon graduated from The University of Sydney in 2008 with a PhD on the photoprotective effects of vitamin D compounds, under Prof. Rebecca Mason. She is now an academic at the University of Sydney with main research interests in vitamin D, photobiology, cancer cell signalling, melanoma and non-melanoma skin cancers.