联合疗法与烟酰胺单一疗法在预防紫外线辐射诱发皮肤癌方面的疗效对比。

IF 3 3区医学 Q2 DERMATOLOGY

Dermatology Pub Date : 2024-04-10 DOI:10.1159/000538445

Celina Pihl, F. Andersen, Peter Bjerring, M. Haedersdal, C. Lerche

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引用次数: 0

摘要

简介紫外线辐射（UVR）是角质细胞癌（KC）的主要风险因素。据报道，口服烟酰胺（NAM；NAM-mono）可减少新的 KC 的形成。NAM 的光保护作用是通过增强 DNA 修复来实现的。我们希望探索将 NAM 与抗增殖（二甲双胍；Met）或抗氧化（氯葡萄糖醇；PG）化合物结合使用是否有可能增强其光保护作用。方法用标准剂量的 NAM 单药（600 毫克/千克）或 NAM（400 毫克/千克）与 Met（200 毫克/千克）（NAM-Met）或 PG（75 毫克/千克）（NAM-PG）联合口服治疗无毛小鼠（C3.Cg-Hrhr/TifBomTac）。每周用 3.5 标准红斑剂量的紫外线照射小鼠三次，以诱导肿瘤发生。光保护作用基于 i) 前三个肿瘤的发病情况；ii) 皮肤光损伤；iii) DNA 损伤（环丁烷嘧啶二聚体 [CPDs] 和嘧啶-嘧啶酮（6-4）光产物 [6-4PPs]）。结果与紫外线对照组相比，所有接受 NAM 治疗的小鼠的肿瘤发病时间均有所推迟，肿瘤负荷也有所减轻（NAM、NAM-Met、NAM-PG 与紫外线对照组相比：P ≤ 0.015）。NAM-mono 和 NAM-PG 延长了所有三种肿瘤的生长时间，但它们之间没有差异，这表明它们的光保护程度相似。与紫外线对照组相比，NAM-mono 对 DNA 损伤没有影响（p > 0.05），而与 NAM-mono 相比，NAM-PG 可减少 6-4PP 病变（p < 0.01），但不能减少 CPD（p > 0.05）。与紫外线对照组相比，NAM-Met 可延缓第三个肿瘤的发生，但与 NAM-mono 相比，NAM-Met 的发生速度更快，这表明与烟酰胺单一疗法相比，NAM-PG 的光保护效果更差。6-4PP 病变的减少可能表明，NAM-PG 的光保护机制比 NAM-mono 更为适合。NAM-mono 优于 NAM-Met，这表明 NAM 的光保护作用与剂量有关。这些结果凸显了结合光保护化合物以增强光保护作用的潜力。

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Efficacy of combinational treatment versus nicotinamide monotherapy in the prevention of ultraviolet radiation-induced skin cancer.

INTRODUCTION Ultraviolet radiation (UVR) is the primary risk factor for keratinocyte carcinomas (KC). Oral supplementation with nicotinamide (NAM; NAM-mono) is reported to reduce the formation of new KCs. NAM's photoprotection is mediated by enhanced DNA repair. We wanted to explore whether NAM in combination with anti-proliferative (Metformin; Met) or antioxidant (Phloroglucinol; PG) compounds could potentially enhance its photoprotective effects. METHODS Hairless mice (C3.Cg-Hrhr/TifBomTac) were treated orally with either a standard dose of NAM monotherapy (600 mg/kg), or NAM (400 mg/kg) combined with Met (200 mg/kg) (NAM-Met) or PG (75 mg/kg) (NAM-PG). Mice were irradiated with 3.5 standard erythema doses of UVR three times per week to induce tumour development. Photoprotective effects were based on i) tumour onset of the first three tumours, ii) skin photodamage, and iii) DNA damage (cyclobutane pyrimidine dimers [CPDs] and pyrimidine-pyrimidone (6-4) photoproducts [6-4PPs]). RESULTS All mice treated with NAM demonstrated a delay in tumour onset and reduced tumour burden compared to the UV control group (NAM, NAM-Met, NAM-PG vs. UV control: p ≤ 0.015). NAM-mono and NAM-PG increased time until all three tumours with no difference between them, indicating a similar degree of photoprotection. NAM-mono had no effect on DNA damage compared to the UV control group (p > 0.05), whereas NAM-PG reduced 6-4PP lesions (p < 0.01), but not CPDs (p > 0.05) compared to NAM-mono. NAM-Met delayed the onset of the third tumour compared to the UV control but demonstrated a quicker onset compared to NAM-mono, suggesting inferior photoprotection compared to nicotinamide monotherapy. CONCLUSION NAM-PG was as effective in delaying UVR-induced tumour onset as NAM-mono. The reduction in 6-4PP lesions may indicate that the mechanism of NAM-PG is better suited for photoprotection than NAM-mono. NAM-mono was superior to NAM-Met, indicating a dose-dependency of NAM's photoprotection. These results highlight a potential for combining photoprotective compounds to enhance photoprotection.

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来源期刊

Dermatology 医学-皮肤病学

CiteScore

6.40

自引率

2.90%

发文量

审稿时长

1 months

期刊介绍： Published since 1893, ''Dermatology'' provides a worldwide survey of clinical and investigative dermatology. Original papers report clinical and laboratory findings. In order to inform readers of the implications of recent research, editorials and reviews prepared by invited, internationally recognized scientists are regularly featured. In addition to original papers, the journal publishes rapid communications, short communications, and letters to ''Dermatology''. ''Dermatology'' answers the complete information needs of practitioners concerned with progress in research related to skin, clinical dermatology and therapy. The journal enjoys a high scientific reputation with a continually increasing impact factor and an equally high circulation.