SKINCARE
was correlated with the concentration of the peroxide.19,20
Other skin conditions There is evidence from studies in experimental animals that lipid peroxides can cause apoptosis (programmed cell death) of hair follicle cells in alopecia, and increased concentrations have been described in the lesions of seborrheic dermatitis, acne rosacea, and psoriasis.
Implications for skincare The collective evidence from laboratory, experimental, and clinical studies clearly points to a significant contribution of lipid peroxidation products to the development of at least four skin conditions – the ageing changes, sunburn, skin cancers, and acne vulgaris. Yet there is currently no skincare technology
that directly targets them. The UK start-up company Kutanios, an alumnus of the SOSV Indie Bio Accelerator in New York, was created with the aim of developing skincare molecules that block the harmful effects of lipid peroxides. In an example of technology transfer from
cardiovascular medicine to skincare, the starting point was to take small peptides that were already known to protect cultured vascular cells from lipid peroxides by binding them with high affinity. When the first ones tested by Kutanios were found to have properties that rendered them unsuitable for skincare, modifications were made, leading eventually to the development of their lead peptide LipoxErase™. In proof-of-concept studies, the peptide
protected cultured skin cells from all the measured harmful effects of UV-irradiation, despite having no intrinsic anti-oxidant activity in the non-cellular ORAC assay. In fibroblasts, addition of the peptide to the medium substantially reduced the UV-induced increases in the secretion rates of MMP-1 and inflammatory cytokines. In UV-irradiated keratinocytes, the formation of 8-OHdG in DNA, the production of MDA, and the production of protein adducts with 4-HNE were all blocked (Figure 2). A preliminary clinical study in subjects with
acne also yielded positive results. In 24 subjects aged 15-41 years, a statistically significant reduction in the number of comedones was observed after daily application of the peptide in a simple cosmetic serum for 28 days. In a post hoc analysis of the 18 subjects
who were 30 years of age or less, statistically significant reductions of about 25% were observed also in the total perimeter, surface area, and elevation of the comedones, quantified using a 3D structured-light scanner (Figure 3). The peptide has been shown to be non-
allergenic, is completely biodegradable, and will be manufacturable by green technology. Patents are pending. The company is planning to enter commercialisation by 2024.
PC
References 1. Zastrow L, Lademann J. Light - instead of UV Protection: new requirements for skin cancer prevention. Anticancer Res. 2016; 36: 1389-94
www.personalcaremagazine.com 150 p<0.01 100 24 SUBJECTS
61
50
0 Day 0 Day 28
Figure 3: Effects of LipoxErase peptide on the number of comedones in subjects with acne vulgaris. The peptide was applied twice daily in a simple cosmetic serum for 28 days. Results are expressed relative to the group mean on Day 0
2. Fussell JC, Kelly FJ. Oxidative contribution of air pollution to extrinsic skin ageing. Free Rad. Biol. Med. 2020; 151: 111-22
3. Iuchi K, Takai T, Hisatomi H. Cell death via lipid peroxidation and protein aggregation. Biology (Basel). 2021. doi: 10.3390/ biology10050399
4. Hiraoka K, Sasaguri Y, Komiya S, Zenmyo M, Inoue A, Morimatsu M. Effects of lipid peroxide on production of matrix metalloproteinase 1 (tissue collagenase) and 3 (stromelysin) and tissue inhibitor metalloproteinase 1 by human rheumatoid synovial fibroblasts. Exp. Mol. Pathol. 1993. doi: 10.1006/exmp.1993.1036
5. Ansary TM, Hossain R, Kamiya K, Komine M, Ohtsuki M. Inflammatory molecules associated with ultraviolet radiation- mediated skin aging. Int. J. Mol. Sci. 2021.
https://doi.org/10.3390/ijms22083974
6. Sisignano M, Angioni C, Ferreiros N et al. Synthesis of lipid mediators during UVB- induced inflammatory hyperalgesia in rats and mice. PLoS ONE. 2013. doi: 10.1371/ journal.pone.0081228
7. Moan J, Dahlback A. The relationship between skin cancers, solar radiation and ozone depletion. Br. J. Cancer. 1992; 65: 916-21
8. Valavanidis A, Vlachogianni T, Fiotakis C. 8-hydroxy-2’ -deoxyguanosine (8-OHdG): a critical biomarker of oxidative stress and carcinogenesis. J. Environ. Sci. Health C. Environ. Carcinog. Ecotoxicol. Rev. 2009. doi: 10.1080/10590500902885684
9. Huang H, Kozekov ID, Kozekova A. DNA Cross-links Induced by trans-4- Hydroxynonenal. Environ. Mol. Mutagen. 2010; 51: 625-34. doi: 10.1002/em.20599
10. Chang D, Shain AH. The landscape of driver mutations in cutaneous squamous cell carcinoma. Genom. Med. 2021. doi: 10.1038/ s41525-021-00226-4
11. Heppt MV, Siepmann T, Engel J et al. Prognostic significance of BRAF and NRAS mutations in melanoma: a German study
from routine care. BMC Cancer. 2017. doi: 10.1186/s12885-017-3529-5
12. Pellegrini C, Maturo MG, Di Nardo L et al. Understanding the molecular genetics of basal cell carcinoma. Int. J. Mol. Sci. 2017. doi: 10.3390/ijms18112485
13. Heidenreich B, Denisova E, Rachakonda S et al. Genetic alterations in seborrheic keratoses. Oncotarget. 2017. doi: 10.18632/ oncotarget.16698
14. McLaughlin J, Watterson S, Layton AM et al. Propionibacterium acnes and acne vulgaris: new insights from the integration of population genetic, multi-omic, biochemical and host-microbe studies. Microorganisms. 2019. doi: 10.3390/microorganisms7050128
15. Tochio T, Tanaka H, Nakata S, Ikeno H. Accumulation of lipid peroxide in the content of comedones may be involved in the progression of comedogenesis and inflammatory changes in comedones. J. Cos. Derm. 2009; 8: 152-8
16. Capitanio B, Lora V, Ludovici M et al. Modulation of sebum oxidation and interleukin-1α levels associates with clinical improvement of mild comedonal acne. JEADV. 2014. doi: 10.1111/jdv.12431
17. Ottaviani M, Alestas T, Fiori E, Mastrofrancesco A, Zouboulis C, Picardo M. Peroxidated squalene induces the production of inflammatory mediators in HaCaT keratinocytes: a possible role in acne vulgaris. J. Invest. Derm. 2006; 126: 2430-7
18. Picardo M, Zompetta C, De Luca C et al. Squalene peroxides may contribute to ultraviolet light-induced immunological effects. Photoderm. Photoimmunol. Photomed. 1991; 8:105-10
19. Chiba K, Yoshizawa K, Makino I, Kawakami K, Onoue M. Comedogenicity of squalene mono-hydroperoxide in the skin after topical application. J. Tox. Sci. 2000; 25: 77-83. doi: 10.2131/jts.25.77
20. Motoyoshi K. Enhanced comedo formation in rabbit ear skin by squalene and oleic acid peroxides. Br. J. Dermatol. 1983; 109: 191-8
March 2023 PERSONAL CARE
Number of comedones
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