Isoflavone genistein: photoprotection and clinical implications in dermatology.

Genistein is a soybean isoflavone with diverse biological activities. It is a potent antioxidant, a specific inhibitor of protein tyrosine kinase, and a phytoestrogen. In recent years, increasing evidence has accumulated that this natural ingredient shows preventative and therapeutic effects for breast and prostate cancers, postmenopausal syndrome, osteoporosis, and cardiovascular diseases in animals and humans. In the past decade we have conducted a series of studies and demonstrated that genistein has significant antiphotocarcinogenic and antiphotoaging effects. Genistein substantially inhibits skin carcinogenesis and cutaneous aging induced by ultraviolet (UV) light in mice, and photodamage in humans. The mechanisms of action involve protection of oxidative and photodynamically damaged DNA, downregulation of UVB-activated signal transduction cascades, and antioxidant activities. In this article, we review the biological activities of genistein, as well as published and unpublished research from our laboratory. In addition, we discuss the potential application of genistein to clinical dermatology.

Interleukin balance and early recovery from anesthesia in elderly surgical patients exposed to beta-adrenergic antagonism.

STUDY OBJECTIVE: To determine whether proinflammatory and antiinflammatory cytokines, as measured in blood specimens, would correlate with improved SF-36 physical composite scores observed in elderly surgical patients who were administered perioperative atenolol. DESIGN: Post hoc analysis of data from a randomized clinical study. SETTING: Department of Anesthesiology, Mount Sinai Medical School, New York. PATIENTS: 59 ASA physical status II, III, and IV patients > or =65 years of age, who were scheduled for major elective noncardiac surgery. INTERVENTIONS: Patients were randomized to one of three anesthetic regimens to receive 1) perioperative management without beta-adrenergic antagonism, 2) preoperative and postoperative administration of atenolol, or 3) intraoperative atenolol as a major component of the anesthetic regimen. MEASUREMENTS AND MAIN RESULTS: Blood samples were drawn perioperatively at seven different time points. Interleukin-1 beta, interleukin-6, interleukin-1ra, and interleukin-10 were measured using enzyme-linked immunosorbent assay (ELISA) kits. Also, recovery from anesthesia and physical/mental well-being (SF-36 questionnaire) were determined perioperatively. Compared with control patients, atenolol-treated patients experienced improved postoperative physical well-being, which paralleled the previously reported faster recovery from anesthesia and a decreased need for perioperative analgesics. Improved postoperative physical well-being of atenolol-treated patients was specifically caused by an ameliorated bodily pain score, a major component of the physical composite score of the SF-36 questionnaire. The cytokine response of these elderly surgical patients was similar to that of younger patients, and the perioperative profile of proinflammatory and antiinflammatory cytokines was not affected by atenolol. CONCLUSIONS: Perioperative administration of atenolol to elderly surgical patients markedly improves physical sense of well-being, which coincides with improved postoperative pain control and decreased analgesic requirements. This improvement experienced by patients receiving atenolol is not related to alterations in perioperative cytokine response.

Synergistic enhancement of H2O2 production in human epidermoid carcinoma cells by Benzo[a]pyrene and ultraviolet A radiation.

Benzo[a]pyrene (BaP) is an ubiquitous environmental pollutant with potential carcinogenecity. It was shown that BaP, upon irradiation by UV A, enhanced the formation of 8-hydroxy-2'-deoxyguanosine in purified DNA and in cultured cells. The purpose of this present study was to determine whether BaP and UV radiation synergistically generate reactive oxygen species (ROS) that consequently result in the oxidation of DNA bases. In this study, the levels of H(2)O(2) were measured as an indicator of ROS in A431 cells and primary human keratinocytes treated with BaP plus UV radiation. Production of H(2)O(2) significantly increased from cells treated with BaP plus UVB or UVA, with the latter having a much greater effect. The responses of A431 cells and primary human keratinocytes to BaP and UVA irradiation were similar in generation of extracellular H(2)O(2). Also, H(2)O(2) production proportionally correlated with UVA and UVB dose, but was independent of time or BaP concentration. Treatment with catalase and general ROS scavengers significantly decreased H(2)O(2) production from cells treated with BaP plus UVA, whereas scavengers of *O2-, *OH, and (1)O(2) had minimal effects. These results demonstrate that BaP synergistically enhances the production of H(2)O(2) from cultured cells by UVA and, to a lesser extent, by UVB, supporting the hypothesis that interaction of BaP and UVA can generate ROS and further substantiate oxidative DNA damage that may lead to carcinogenesis.

Effects of the isoflavone 4',5,7-trihydroxyisoflavone (genistein) on psoralen plus ultraviolet A radiation (PUVA)-induced photodamage.

Long-term psoralen plus ultraviolet A radiation (PUVA) therapy is associated with an increased risk of squamous cell carcinoma and malignant melanoma. Genistein (4',5,7-trihydroxyisoflavone), a major isoflavone in soybeans and a specific inhibitor of protein tyrosine kinase, has been shown to inhibit UVB induced skin carcinogenesis in hairless mice. For this study we examined the protective effects of topical genistein on PUVA-induced photodamage. In two separate experiments, genistein in a dimethyl sulfoxide/acetone (1:9) solution was applied to SKH-1 female mice 1 h post 8-methoxy-psoralen dosing and 1 h prior to UVA irradiation. Application of genistein significantly decreased PUVA-induced skin thickening, and greatly diminished cutaneous erythema and ulceration in a dose-dependent manner. Histological examination showed that PUVA treatment of mouse skin induced dramatic inflammatory changes throughout the epidermis; topical genistein prevented these changes without noticeable adverse effects. Cells containing cleaved poly(ADP-ribose) polymerase (PARP) and active caspase-3 were significantly increased in PUVA-treated skin (P < 0.05 and P < 0.0001, respectively) as compared with unexposed control skin. Topical genistein completely inhibited cleavage of PARP and caspase-3. Proliferating cell nuclear antigen (PCNA) positive cells were observed in suprabasal areas of the epidermis and were significantly decreased in PUVA-treated skin compared with both control samples and samples treated with PUVA plus topical genistein (P < 0.005). These results indicate that genistein protects the skin from PUVA-induced photodamage.