Mendonça Graziela Hermínia Andrade, Reis Aline Chaves, Konig Isaac Filipe Moreira, Brito Gabriela Pereira, Rodrigues José Henrique Silva, Guimarães Camila Souza de Oliveira, Mati Vitor Luís Tenório, Remedio Rafael Neodini
Department of Medicine, Federal University of Lavras, Minas Gerais, Brazil.
Department of Veterinary Medicine, Federal University of Lavras, Minas Gerais, Brazil.
Toxicol Rep. 2024 Nov 26;13:101834. doi: 10.1016/j.toxrep.2024.101834. eCollection 2024 Dec.
Carvacrol, a phenolic monoterpene found in essential oils of plants of the Lamiaceae family, emerges as an alternative acaricide of plant origin. Its acetylation was proposed to obtain a derivative compound with a better pharmacological profile and lower toxicity to non-target organisms. The present study aimed to assess the preclinical safety of acetylcarvacrol after dermal application in Wistar rats, through the examination of hematological and biochemical parameters, as well as histopathological analysis of the skin, liver and kidney. For this, twenty rats were distributed into four groups with five animals each. Three groups received treatment with different concentrations of the substance (26, 52, and 104 µL/mL) based on the lethal concentration for ticks, and one group (Control) received only the vehicle. Acetylcarvacrol was applied daily to a trichotomized skin area for 21 days. No changes in hematological parameters were observed. Regarding biochemical analysis, a slight increase in urea and alanine transaminase levels was noted. No significant changes were observed in the kidney and liver, although the rats had developed cumulative irritant contact dermatitis at the application site, as corroborated by the histopathological analysis of the skin. In general, the results showed that the dermal application of acetylcarvacrol in the experimental conditions described here is safe. However, it can cause signs of mild systemic toxicity and skin irritation at high concentrations, suggesting that this product should be used in lower therapeutic doses and that the development of less aggressive formulations, including the combination with other acaricides, is desirable.
香芹酚是一种在唇形科植物精油中发现的酚类单萜，是一种植物源杀螨剂替代品。有人提出对其进行乙酰化以获得一种药理特性更好且对非靶标生物毒性更低的衍生物。本研究旨在通过检测血液学和生化参数以及对皮肤、肝脏和肾脏进行组织病理学分析，评估在Wistar大鼠中经皮应用乙酰香芹酚后的临床前安全性。为此，将20只大鼠分为四组，每组五只。三组分别接受基于对蜱的致死浓度的不同浓度该物质（26、52和104µL/mL）的处理，一组（对照组）仅接受赋形剂。每天将乙酰香芹酚应用于三分的皮肤区域，持续21天。未观察到血液学参数变化。关于生化分析，注意到尿素和丙氨酸转氨酶水平略有升高。尽管通过皮肤组织病理学分析证实大鼠在应用部位出现了累积刺激性接触性皮炎，但在肾脏和肝脏中未观察到显著变化。总体而言，结果表明在此处描述的实验条件下经皮应用乙酰香芹酚是安全的。然而，高浓度时它会引起轻度全身毒性和皮肤刺激迹象，这表明该产品应以较低治疗剂量使用，并且开发刺激性较小的制剂，包括与其他杀螨剂联合使用，是可取的。
