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二萜异松油醇的协同抗真菌作用及其体内毒性研究

Synergistic Antifungal Effect and In Vivo Toxicity of a Monoterpene Isoespintanol Obtained from Diels.

机构信息

Biology Department, Faculty of Basic Sciences, University of Córdoba, Montería 230002, Colombia.

Chemistry Department, Faculty of Basic Sciences, University of Córdoba, Montería 230002, Colombia.

出版信息

Molecules. 2024 Sep 17;29(18):4417. doi: 10.3390/molecules29184417.

DOI:10.3390/molecules29184417
PMID:39339412
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11433975/
Abstract

sp. infections are a threat to global health, with high morbidity and mortality rates due to drug resistance, especially in immunocompromised people. For this reason, the search for new alternatives is urgent, and in recent years, a combined therapy with natural compounds has been proposed. Considering the biological potential of isoespintanol (ISO) and continuing its study, the objective of this research was to assess the effect of ISO in combination with the antifungals fluconazole (FLZ), amphotericin B (AFB) and caspofungin (CASP) against clinical isolates of and to evaluate the cytotoxic effect of this compound in the acute phase (days 0 and 14) and chronic phase (days 0, 14, 28, 42, 56, 70 and 84) in female mice () of the Balb/c lineage. The results show that ISO can potentiate the effect of FLZ, AFB and CASP, showing synergism with these antifungals. An evaluation of the mice via direct observation showed no behavioral changes or variations in weight during treatment; furthermore, an analysis of the cytokines IFN-γ and TNF in plasma, peritoneal cavity lavage (PCL) and bronchoalveolar lavage (BAL) indicated that there was no inflammation process. In addition, histopathological studies of the lungs, liver and kidneys showed no signs of toxicity caused by ISO. This was consistent with an analysis of oxaloacetic transaminases (GOT) and pyruvic transaminases (GPT), which remained in the standard range. These findings indicate that ISO does not have a cytotoxic effect at the doses evaluated, placing it as a monoterpene of interest in the search for compounds with pharmacological potential.

摘要

种感染是全球健康的威胁,由于耐药性,发病率和死亡率很高,尤其是在免疫功能低下的人群中。出于这个原因,寻找新的替代品迫在眉睫,近年来,已经提出了天然化合物的联合治疗方法。考虑到异艾杜醇(ISO)的生物潜力并继续对其进行研究,本研究的目的是评估 ISO 与抗真菌药物氟康唑(FLZ)、两性霉素 B(AFB)和卡泊芬净(CASP)联合使用对种临床分离株的作用,并评估该化合物在急性相(第 0 天和第 14 天)和慢性相(第 0 天、第 14 天、第 28 天、第 42 天、第 56 天、第 70 天和第 84 天)对雌性小鼠()的细胞毒性作用。结果表明,ISO 可以增强 FLZ、AFB 和 CASP 的作用,与这些抗真菌药物表现出协同作用。通过直接观察对小鼠进行评估,在治疗过程中没有观察到行为变化或体重变化;此外,对血浆、腹腔灌洗(PCL)和支气管肺泡灌洗(BAL)中的 IFN-γ 和 TNF 细胞因子进行分析表明,没有炎症过程。此外,肺、肝和肾的组织病理学研究显示,ISO 没有引起毒性的迹象。这与草酰乙酸转氨酶(GOT)和丙酮酸转氨酶(GPT)的分析结果一致,它们仍在标准范围内。这些发现表明,在评估的剂量下,ISO 没有细胞毒性作用,这使其成为具有药理潜力的化合物研究中具有潜力的单萜。

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