Topically Applied Eicosapentaenoic Acid Protects Against Local Immunosuppression Induced by UVB Irradiation, cis-Urocanic Acid and Thymidine Dinucleotides¶

Abstract

UVB‐induced immunosuppression, a promoter of photocarcinogenesis, involves the formation of pyrimidine dimers and cis‐urocanic acid (cis‐UCA), but reactive oxygen species (ROS) also plays an important role. Eicosapentaenoic acid (EPA) can inhibit photocarcinogenesis, but due to its polyunsaturated nature it is susceptible to oxidative damage by ROS. The antioxidant defense system may therefore be challenged upon ultraviolet‐B (UVB) irradiation in the presence of EPA. We investigated whether topically applied EPA in mice could protect against local immunosuppression (contact hypersensitivity response to dinitrofluorobenzene) induced by UVB radiation (1.5 J/cm2), or topically applied cis‐UCA (150 nmol/cm2) or thymidine dinucleotides (pTpT) (5 nmol/cm2). The influence of EPA on epidermal lipid peroxidation and antioxidant status was also measured. UVB irradiation, cis‐UCA and pTpT all caused 70% immunosuppression. Topical pretreatment of mice with EPA partially protected against immunosuppression; the EPA dose needed to accomplish this was 10 nmol/cm2 for UVB irradiation, 100 nmol/cm2 for cis‐UCA and 1000 nmol/cm2 for pTpT. Higher EPA doses caused higher UVB‐induced lipid peroxidation and lower vitamin C levels. Glutathione only decreased with the highest EPA dose whereas vitamin E was not decreased after UVB irradiation. In conclusion, topically applied EPA protects against UVB‐, cis‐UCA‐ and pTpT‐induced immunosuppression and maintenance of an adequate antioxidant defense seems to be an important prerequisite for the protective action by EPA.

Randomized controlled trial of oral omega-3 PUFA in solar-simulated radiation-induced suppression of human cutaneous immune responses

“…Our findings were consistent with supplementation studies in animals (14,31) and epidemiologic surveys (8,9) and highlighted a mechanism whereby n23 PUFA supplementation may act to reduce UVR-induced skin cancer risk in humans (32). This study was pertinent because traditional topical sunscreens are less effective at protecting against photoimmunosuppression than against UVR-induced erythema, as indicated by the sun protection factor (33), and they are generally applied inadequately, as well as infrequently, outside of vacation periods (34,35).…”

Dietary, but not Topical, Alpha-linolenic Acid Suppresses UVB-induced Skin Injury in Hairless Mice when Compared with Linoleic Acid¶

“…1). Consistently, Moison et al (21) have shown that topically applied EPA protected against immune suppression, but increased doses of EPA resulted in decreased vitamin C and glutathione levels after UVB irradiation. These results indicate that maintaining an adequate antioxidant defense system is important for the protective effects of PUFA against UVB irradiation.…”

Reversal of ultraviolet B‐induced immunosuppression by inhibition of the extracellular signal‐regulated mitogen‐activated protein kinase

“…The residues of the undecomposed PD in group A or B penetrating into the dermis would probably be insufficient to inhibit phospho‐ERK1/2 MAPK as opposed to PD in group C, which exerted a reversible role against local UVB‐induced immuno‐suppression. Thus, besides vitamins E and C (33), eicosapentaenoic acid (32) and caffeic acid (42), the ERK1/2‐specific inhibitor PD or its analogues might be used potentially against UVB‐induced immunosuppression.…”

“…In our system, previous studies have suggested the protocols of the mouse model of UVB‐induced local immunosuppression (32–36), and the key point on the dose of UVB ranges from 8 to 15 kJ/m 2 (32–34, 37). Thus, different doses of UVB (6, 8, 10, 12, 14 and 16 kJ/m 2 ) were used for irradiation on the depilated abdominal skin in UVB‐tested groups, for an appropriate dose of UVB to induce local immunosuppression in our system.…”