Effect of adenosine triphosphate on ribociclib-induced skin toxicity in rats.

IF 1.6 4区医学 Q3 OPHTHALMOLOGY

Cutaneous and Ocular Toxicology Pub Date : 2023-03-01 DOI:10.1080/15569527.2023.2166524

Nergis Akbaş, Emin Murat Akbaş, Zeynep Süleyman, Betül Çiçek, Ahmet Gökhan Ağgül, Behzad Mokhtare, Halis Süleyman

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引用次数: 1

Abstract

Purpose: Ribociclib is a CDK4/6 inhibitor approved for the treatment of breast cancer; it inhibits the activity of CDK4/6 by competitively binding to adenosine 5'-triphosphate (ATP) binding sites. Although generally well-tolerated, ribociclib has been connected to a number of serious dermatologic complications. This study explored the effects of ATP on ribociclib-induced skin damage.

Materials and methods: Using a rat model, ATP 25 mg/kg was injected intraperitoneally in the ATP + Ribociclib (ATR) group (n = 6). Distilled water as solvent was applied to the healthy control (HC) group (n = 6) and ribociclib (RCB) group (n = 6). One hour after ATP and solvent administration, ribociclib (200 mg/kg) suspension prepared in distilled water was administered to the stomach by gavage (ATR and RCB groups). This was repeated once a day for 15 d. After that period, biochemical markers were studied in the skin tissues and histopathological evaluations were conducted.

Results: In the histopathological evaluation of the RCB group, dermal necrosis, degeneration in hair follicles, and pycnosis in keratinocytes were observed. Only mild degeneration was observed in the ATR group; the HC group had a normal histological appearance. The malondialdehyde (MDA) values were significantly higher and the superoxide dismutase (SOD), catalase (CAT), and total glutathione (tGSH) levels were significantly lower in the RCB group in comparison to the HC group (p < .001). ATP reduced the ribociclib-induced increases in the MDA values and decreased the SOD, CAT, and tGSH levels in the ATR group (p < .001).

Conclusion: ATP may be useful in the treatment of ribociclib-induced skin damage.

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三磷酸腺苷对核环苷所致大鼠皮肤毒性的影响。

目的:Ribociclib是一种被批准用于治疗乳腺癌的CDK4/6抑制剂;它通过竞争性结合腺苷5'-三磷酸(ATP)结合位点来抑制CDK4/6的活性。虽然一般耐受性良好，但核糖环尼与许多严重的皮肤并发症有关。本研究探讨了ATP在核环苷诱导的皮肤损伤中的作用。材料与方法:采用大鼠模型，ATP + Ribociclib (ATR)组(n = 6)腹腔注射ATP 25 mg/kg。健康对照(HC)组(n = 6)和核糖环苷(RCB)组(n = 6)采用蒸馏水作为溶剂。ATP和溶剂给药1小时后，用蒸馏水配制的核糖素(200 mg/kg)混悬液灌胃(ATR组和RCB组)。每天重复一次，持续15 d。在此之后，研究皮肤组织中的生化标志物并进行组织病理学评价。结果:RCB组的组织病理学观察结果为真皮坏死、毛囊变性、角化细胞增生。ATR组仅轻度退变;HC组组织学外观正常。与HC组相比，RCB组丙二醛(MDA)值显著升高，超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和总谷胱甘肽(tGSH)水平显著降低(p)。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cutaneous and Ocular Toxicology 医学-毒理学

CiteScore

3.30

自引率

6.20%

发文量

审稿时长

1 months

期刊介绍： Cutaneous and Ocular Toxicology is an international, peer-reviewed journal that covers all types of harm to cutaneous and ocular systems. Areas of particular interest include pharmaceutical and medical products; consumer, personal care, and household products; and issues in environmental and occupational exposures. In addition to original research papers, reviews and short communications are invited, as well as concise, relevant, and critical reviews of topics of contemporary significance.