501 Administration of nicotinamide riboside (NR) or pterostilbene (PT) to mice inhibits suppression of contact hypersensitivity (CHS) by mid-range ultraviolet radiation (UVR)

Abstract

Topical administration of PT inhibits some acute effects of mid-range UVR (UVBR, 280-320 nm) in mouse skin and oral nicotinamide reduces the rate of new non-melanoma skin cancers in high-risk patients. NR+PT inhibits UVBR-induced tissue swelling in mice and does so more effectively than either agent at the dose tested. We have now asked if NR, PT or the combination can inhibit UVBR suppression of CHS in 2 models. In the low-dose model, mice receive a UVBR dose too low to cause gross changes in skin, followed by immunization at the irradiated site, resulting in suppressed CHS. In the high-dose model, mice receive a dose sufficient to cause gross skin changes followed by immunization at an unirradiated site, also with suppressed CHS. C3H mice were placed in groups that were fed standard diet/water or chow containing 0.08% PT, water with 0.4% NR or both for 4 wks. In low-dose experiments, mice in each group had their dorsa shaved and depilated. Half in each group were exposed to 1,700 J/m2 of UVBR daily for 4 d while the other half were mock-irradiated. Mice were immunized on the exposed dorsum with 25 μl of 0.5% dinitrofluorobenzene (DNFB) 4 h after the last irradiation. Mice were challenged 7 d later with 10 μl of 0.2% DNFB to each ear and 24-h ear swelling assessed. CHS in mice not given PT, NR or both was significantly reduced by UVBR exposure compared to mock-irradiated mice. In mice fed NR, PT, or both the UVBR effect was significantly less pronounced. In a preliminary high-dose experiment, groups of mice were treated similarly except that a single dose of 10,000 J/m2 of radiation was administered and immunization was performed on the unirradiated shaved abdomen 3 d later. In this experiment, the UVBR effect was also significantly less pronounced in the NR, PT or NR+PT groups. NR and PT both inhibited UVB-induced immune suppression at the doses administered as did the combination.