Inhibition of UVB radiation-induced tissue swelling and immune suppression by nicotinamide riboside and pterostilbene

Abstract

Background: Environmental ultraviolet radiation has deleterious effects on humans, including sunburn and immune perturbations. These immune changes are involved in skin carcinogenesis.

Objectives: To determine whether nicotinamide riboside and/or pterostilbene administered systemically inhibits inflammatory and immune effects of exposure to mid-range ultraviolet radiation.

Methods: To examine UVB radiation-induced inflammatory effects, mice were fed standard chow/water, 0.04% pterostilbene in chow and 0.2% nicotinamide riboside in drinking water, diet with nicotinamide riboside alone, or diet with pterostilbene alone. After 4 weeks, mice were exposed to UVB radiation (3500 J/m²), and 24-/48-h ear swelling was assessed. We also asked if each agent or the combination inhibits UVB radiation suppression of contact hypersensitivity in two models. Mice were fed standard diet/water or chow containing 0.08% pterostilbene, water with 0.4% nicotinamide riboside, or both for 4 weeks. Low-dose: Half the mice in each group were exposed on the depilated dorsum to UVB radiation (1700 J/m²) daily for 4 days, whereas half were mock-irradiated. Mice were immunized on the exposed dorsum to dinitrofluorobenzene 4 h after the last irradiation, challenged 7 days later on the ears with dinitrofluorobenzene, and 24-h ear swelling assessed. High dose: 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 days later.

Results: Nicotinamide riboside and pterostilbene together inhibited UVB-induced skin swelling more than either alone. Pterostilbene alone and both given together could inhibit UVB-induced immune suppression in both the low-dose and high-dose models while nicotinamide riboside alone was more effective in the low-dose model than the high-dose model.

Conclusion: Nicotinamide riboside and pterostilbene have protective effects against UVB radiation-induced tissue swelling and immune suppression.

Keywords: animal model; immunity; inflammation; ultraviolet radiation.

Figure 1. Ear Swelling in response to UVB radiation after diet supplemented with and without PS/NR.

Mice were exposed to 3500 J/m² UVB radiation after four weeks of feeding. The graphs shown are a comparison of ear thicknesses at different time points after irradiation less baseline ear thicknesses. Data represent N=10 per group from 2 experiments, mean+/− SEM. **p<0.01, ***p< 0.001 (experimental diet groups compared to standard diet). Abbreviations: PT, pterostilbene; NR, nicotinamide riboside.

Figure 2.. Ear swelling in response to UVB radiation after diet supplemented with and without PT/NR.

Mice were exposed to 3500 J/m² UVB radiation after four weeks of feeding. The graphs shown are a comparison of ear thicknesses at different time points after irradiation less baseline ear thicknesses. Data represent N=10 per group from 2 experiments, mean +/− SEM. ***p<0.001 (other diet groups compared to 0% NR/0% PS). Abbreviations: PT, pterostilbene; NR, nicotinamide riboside.

Figure 3.. Effect of PT/NR on suppression of contact hypersensitivity by UVB radiation in the local model.

Mice were exposed to 1700 J/m² UVB radiation on four consecutive days after four weeks of feeding, then immunized at the irradiated site with DNFB and CHS was elicited subsequently. The graphs shown are a comparison of ear thicknesses at different time points after irradiation minus baseline ear thicknesses. Data represent N=10 per group from 2 experiments, except std, UV-, DNFB- group is N=5 from one experiment mean +/− SEM. NS= not significant, ***p<0.001 (compared to standard diet group). Abbreviations: std, standard; UV, ultraviolet; PT, pterostilbene, NR, nicotinamide riboside; DNFB, dinitrofluorobenzene.

Figure 4.. Effect of PT/NR or each agent alone on suppression of contact hypersensitivity by UVB radiation in the local model.

Mice were exposed to 1700 J/m² UVB radiation on four consecutive days after four weeks of feeding, then immunized on the irradiated site with DNFB and CHS was elicited subsequently. The graphs shown are a comparison of ear thicknesses at different time points after irradiation minus baseline ear thicknesses. Data represent N=10 per group from 2 experiments, mean +/− SEM. NS=not significant, *p<0.05, ***p<0.001 (compared to standard diet group). Abbreviations: NR, nicotinamide riboside; ultraviolet; PT, pterostilbene; UV, ultraviolet; std, standard; DNFB, dinitrofluorobenzene.

Figure 5.. Effect of PT/NR or each agent alone on suppression of contact hypersensitivity by UVB radiation in the systemic model.

Mice were exposed to 10,000 J/m² UVB radiation on the dorsum after four weeks of feeding; then, mice were immunized on a non-irradiated site (abdomen) with DNFB and CHS was elicited subsequently. The graphs shown are a comparison of ear thicknesses at different time points after irradiation minus baseline ear thicknesses. Data represent N=10 per group from 2 experiments except N=9 from 2 experiments for the std UV−, DNFB− group, mean +/− SEM. NS=not significant, **p< 0.01, ***p<0.001 (compared to standard diet group). Abbreviations: std, standard; UV, ultraviolet; NR, nicotinamide riboside; PT, pterostilbene; DNFB, dinitrofluorobenzene.