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槲皮素和开环异落叶松脂醇内酯治疗肝阿米巴脓肿发展的毒理学评价

Toxicological Evaluation of Kaempferol and Linearolactone as Treatments for Amoebic Liver Abscess Development in .

机构信息

Facultad de Ciencias Químicas (FCQ), Universidad Autónoma de Chihuahua (UACH), Chihuahua 31125, CP, Mexico.

Unidad de Investigación Médica en Farmacología, Hospital de Especialidades UMAE-CMNSXXI-IMSS, Ciudad de México 06725, CP, Mexico.

出版信息

Int J Mol Sci. 2024 Oct 2;25(19):10633. doi: 10.3390/ijms251910633.

Abstract

Several studies with kaempferol (KP) and linearolactone (LL) have demonstrated their antiparasitic activity. However, the toxicity of these treatments is unknown. Therefore, this study aimed to evaluate the possible toxicological effects of intraperitoneal (i.p.) administration of KP or LL on the amoebic liver abscess model (ALA) in . An ALA was induced in male hamsters with 1.5 × 10 () trophozoites inoculated in the left hepatic lobe. The lesion evolved for 4 days, and then KP (5 mg/kg body weight/day) or LL (10 mg/kg body weight/day) was administered for 4 consecutive days. Then, magnetic resonance imaging (MRI), paraclinical analyses, and necropsy for histopathological evaluation were performed. There was similar ALA inhibition by KP (19.42%), LL (28.16%), and metronidazole, the antiamoebic control (20.87%) ( ≤ 0.05, analysis of variance [ANOVA]). There were hepatic and renal biochemical alterations in all treatment groups, mainly for KP (aspartate aminotransferase: 347.5 ± 37.5 U/L; blood urea nitrogen: 19.4 ± 1.9 g/dL; ≤ 0.05, ANOVA). Lesions found in the organs were directly linked to the pathology. In conclusion, KP and LL decreased ALA development and exerted fewer toxicological effects compared with metronidazole. Therefore, both compounds exhibit therapeutic potential as an alternative treatment of amoebiasis caused by . However, additional clinical studies in different contexts are required to reaffirm this assertion.

摘要

几项关于山奈酚 (KP) 和线性内酯 (LL) 的研究已经证明了它们的抗寄生虫活性。然而,这些治疗方法的毒性尚不清楚。因此,本研究旨在评估腹腔内 (i.p.) 给予 KP 或 LL 对. 的阿米巴肝脓肿模型 (ALA) 的可能毒理学影响。用 1.5 × 10 () 滋养体接种在左肝叶中诱导 ALA。病变在 4 天内进展,然后连续 4 天给予 KP(5 mg/kg 体重/天)或 LL(10 mg/kg 体重/天)。然后进行磁共振成像 (MRI)、临床前分析和尸检以进行组织病理学评估。KP(19.42%)、LL(28.16%)和甲硝唑(抗阿米巴对照,20.87%)对 ALA 的抑制作用相似(≤0.05,方差分析 [ANOVA])。所有治疗组均存在肝肾功能生化改变,主要是 KP(天门冬氨酸氨基转移酶:347.5 ± 37.5 U/L;血尿素氮:19.4 ± 1.9 g/dL;≤0.05,ANOVA)。在器官中发现的病变与病理学直接相关。总之,与甲硝唑相比,KP 和 LL 降低了 ALA 的发展并产生了较少的毒理学作用。因此,这两种化合物都具有作为. 引起的阿米巴病替代治疗的潜在治疗作用。然而,需要在不同背景下进行更多的临床研究来证实这一说法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2a9/11477209/e224c9d5e5c2/ijms-25-10633-g001.jpg

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