Photoaged skin caused by chronic ultraviolet radiation (UVR) is characterised clinically with hyperpigmentation, coarse skin texture and deep wrinkles; the worst outcome is skin cancer. Histological investigation of the alteration within major extracellular matrices (ECM; elastic fibres, fibrillar collagens) is essential study to understand the cellular effect on skin structure from UVR. This thesis used an acute dose of radiation to examine in humans in vivo the effect of UVR on ECM components before assessing whether a dietary intervention could protect skin from UVR damage. Green tea catechins (GTCs) have anti-oxidant properties and may be an interesting option as a systemic photoprotection agent. Hence this thesis assesses: 1) the effect of acute irradiation of skin on dermal ECM damage to see whether it mimics the changes observed in photoageing and; 2) whether dietary supplementation with GTC will provide dermal ECM protection. UV-induced change in elastic fibre network. Initially, the effect of two different UV light sources on elastic fibre protein (elastic fibres, fibrillin-rich microfibrils and fibulin-2 and -5 microfibrils) remodelling was performed. The effect of ultraviolet B vs full-spectrum solar simulated radiation (SSR) were investigated in a small sample of healthy Caucasian volunteers (n = 6 per group). At 24 hour after 3× MED irradiation, Weigert's resorcin–fuchsin stained elastic fibres showed a significant reduction regardless of irradiation protocol (UVB, P<0.01; SSR P<0.05). Specific components were identified by immunohistochemistry; a significant reduction in fibrillin-rich microfibrils (FRM) was observed in UVB-irradiated skin (P<0.05), whilst fibulin-5-positive microfibrils were only affected by SSR (P<0.05). The data revealed, therefore, differential effects on UV wavelength on ECM remodelling. SSR, the more physiologically relevant light source was used in subsequent studies Supplement effect in SSR-induced damage in elastic fibre. Fifty healthy volunteers were recruited to this randomised control trial to investigate whether GTC can protect skin from photodamage. Volunteers were randomized to GTC (1080 mg plus 100 mg vitamin C; n=25) or placebo (maltodextrin; n = 25) daily for 12-weeks with compliance assessed biochemically in urine samples. Of the n = 50 recruited, 44 volunteers completed the study. In baseline, UVR challenge resulted in a significant remodeling of the cutaneous elastic fiber system (P<0.001), particularly fibulin-2 and fibulin-5-positive microfibrils at 24-hr after 3×MED irradiation. In post-supplementation, fibulin-5 positive microfibrils were protected from UVR remodeling (% staining, mean ± SE; no UV, 18.1±0.89; UVR, 17.1±0.61; P=0.30) whilst no protection was seen in the placebo group (no UVR, 19.41±0.79; UVR, 17.69±0.61; P<0.05). Supplement effect in SSR-induced damage in collagenous matrix. In the identical experiment, collagenous matrices including synthesis of procollagen I was also examined as fibrillar collagens are the major ECM components providing strength within dermis. The fibrillar collagen and newly synthesised procollagen I were stained by Picrosirius red and immunohistochemistry respectively. At baseline, acute irradiation significantly reduced papillary dermal fibrillar collagens (P<0.001) and induced deposition of newly synthesised pro-collagen I (P=0.02). In post-supplementation, GTC enhanced the deposition of thin collagen fibres in the dermis. Whilst placebo showed no effect on the altered organisation of fibrillar collagens or deposition of pro-collagen I following the irradiation challenge, GTC protected the organisation of fibrillar collagens in the papillary dermis (P=0.97).This novel in vivo human study may be used to recapitulate elastic fibre and collagen changes associated with photoageing and may be useful for dissecting out the mechanisms underlying extracellular matrix damage in response to chronic sunlight exposure. Furthermore, in a randomized control trial, dietary GTC protected fibulin-5 microfibrils and collagen fibres in the papillary dermis from UV-mediated degradation. The mechanism by which this protection occurs requires further study.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:697802 |
| Date | January 2016 |
| Creators | Charoenchon, Nisamanee |
| Contributors | Watson, Rachel ; Rhodes, Lesley ; Farrar, Mark |
| Publisher | University of Manchester |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | https://www.research.manchester.ac.uk/portal/en/theses/can-green-tea-catechin-supplement-protect-against-photoageing(64eefb5f-ef37-4900-9c03-3477c8a74e50).html |
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