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  • [Mar Drugs.] Topical Application of Phlorotannins from Brown Seaweed Mitigates Radiation Dermatitis in a Mouse Model

    [Mar Drugs.] Topical Application of Phlorotannins from Brown Seaweed Mitigates Radiation Dermatitis in a Mouse Model

    성균관의대 / 양경미, 김신영, 박희철*, 최창훈*

  • 출처
    Mar Drugs.
  • 등재일
    2020 Jul 22
  • 저널이슈번호
    18(8):E377. doi: 10.3390/md18080377.
  • 내용

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    Abstract
    Radiation dermatitis (RD) is one of the most common side effects of radiotherapy; its symptoms progress from erythema to dry and moist desquamation, leading to the deterioration of the patients' quality of life. Active metabolites in brown seaweed, including phlorotannins (PTNs), show anti-inflammatory activities; however, their medical use is limited. Here, we investigated the effects of PTNs in a mouse model of RD in vivo. X-rays (36 Gy) were delivered in three fractions to the hind legs of BALB/c mice. Macroscopic RD scoring revealed that PTNs significantly mitigated RD compared with the vehicle control. Histopathological analyses of skin tissues revealed that PTNs decreased epidermal and dermal thickness compared with the vehicle control. Western blotting indicated that PTNs augmented nuclear factor erythroid 2-related factor 2 (NRF2)/heme oxygenase-1 (HO-1) pathway activation but attenuated radiation-induced NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) and inflammasome activation, suggesting the mitigation of acute inflammation in irradiated mouse skin. PTNs also facilitated fast recovery, as indicated by increased aquaporin 3 expression and decreased γH2AX (histone family member X) expression. Our results indicate that topical PTN application may alleviate RD symptoms by suppressing oxidative stress and inflammatory signaling and by promoting the healing process. Therefore, PTNs may show great potential as cosmeceuticals for patients with cancer suffering from radiation-induced inflammatory side effects such as RD.

     

     

    Figure 1. Effects of the topical application of phlorotannins (PTNs) on radiation dermatitis: (a) Schematic of the experimental procedures. Right hind legs were irradiated with X-rays at a dose of 12 Gy per day for three consecutive days (total, 36 Gy). PTNs were dissolved at the indicated concentrations in sesame oil and topically applied to the irradiated skin area starting on the irradiation day. An rhEGF solution was used as the positive control. (b) Representative photographs of the irradiated skin treated with topical PTNs or rhEGF. (c) Time-course of changes in RD score: Data are shown as mean ± SD from three independent experiments. Difference was evaluated using one-way analysis of variance (ANOVA), followed by Bonferroni’s multiple comparison test. *p < 0.05; **p < 0.01; ***p < 0.001.

     

    Figure 2. Phlorotannins (PTNs) reduce the radiation-induced thickening of the epidermis and dermis. (a,b) Representative images of hematoxylin and eosin (H&E) and Masson’s trichrome staining of the irradiated skin tissues; The skin area was topically treated with 0%, 0.05%, and 0.5% PTN or EGF. The skin tissues were collected 14 (a) and 21 (b) days after irradiation. (c,d) Measurement of the epidermal and dermal thickness in the skin tissues collected 14 (c) and 21 (d) days after irradiation: Data are shown as mean ± SD. (n ≥ 40). Difference was evaluated using one-way ANOVA followed by Bonferroni’s multiple comparison test. **p < 0.01; ***p < 0.001.

     

    Figure 3. Phlorotannins (PTNs) mitigate radiation dermatitis by modulating the NRF2 and NF-kB signaling pathways: Skin tissue samples were collected 14 and 21 days after irradiation and subjected to western blotting. (a) Western blotting revealed that PTNs further enhanced the radiation-induced increase in NRF2/HO-1 expression on day 14. (b) PTNs attenuated the radiation-induced activation of the NF-kB pathway and inflammasome. (c) PTNs augmented radiation-induced aquaporin 3 (AQP3) expression but suppressed γH2AX expression in the irradiated tissues. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was used as a loading control.

     

     

    Affiliations

    Kyungmi Yang  1   2 , Shin-Yeong Kim  1 , Ji-Hye Park  2   3 , Won-Gyun Ahn  1 , Sang Hoon Jung  1 , Dongruyl Oh  1   2 , Hee Chul Park  1   2 , Changhoon Choi  1
    1 Department of Radiation Oncology, Samsung Medical Center, Seoul 06351, Korea.
    2 School of Medicine, Sungkyunkwan University, Seoul 06351, Korea.
    3 Department of Dermatology, Samsung Medical Center, Seoul 06351, Korea.

  • 키워드
    inflammation; mouse model; phlorotannins; radiation dermatitis.
  • 연구소개
    방사선 피부염은 방사선 치료로 인한 가장 흔한 부작용 중의 하나로, 방사선치료를 받는 동안 혹은 그 이후 통증, 작열감과 같은 증상을 야기하고 환자의 삶의 질을 떨어뜨리는 요인으로 작용합니다. 이를 예방하거나 치료하기 위해 임상에서는 경험적으로 스테로이드 연고 혹은 일반적인 스킨 케어를 적용하고 있고, 최근 rhEGF 등과 같은 유효성분을 포함한 제품들이 환자들을 대상으로 한 임상연구를 바탕으로 출시되어 코스메슈티컬(cosmeceuticals)로 자리 잡았습니다. 그러나 현존하는 치료제 혹은 스킨케어 제품들에 대한 방사선피부염 예방/치료의 근거와 효과는 여전히 미흡한 상황입니다. 이에 본 연구에서는 갈조류에서 추출한 천연 물질인 Phlorotannin이 항산화, 항염증 작용이 있는 것에 착안하여 방사선피부염을 줄일 수 있는지에 대한 동물실험을 진행하였습니다. 마우스모델에 방사선조사 후 Phlorotannin을 도포했을 때 방사선피부염의 발생 강도가 더 낮았으며 또한 조기 회복하였고, 염증 및 부종으로 인한 표피 및 진피의 두께 증가 역시 적었습니다. 그리고 Phlorotannin 도포 시 NRF2의 증가, AQP3 증가, NF-κB 감소 등을 확인하여, 방사선으로 인한 염증 반응을 낮추고 산화 스트레스를 줄이는 기전을 증명하였습니다. 본 연구는 Phlorotannin의 방사선피부염 예방 및 치료제, 혹은 코스메슈티컬의 유효물질로서의 가능성을 확인한 것에 의의를 둘 수 있습니다.
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