Department of Urology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, China (mainland).
Department of Urology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China (mainland).
Med Sci Monit. 2019 May 17;25:3662-3667. doi: 10.12659/MSM.913637.
BACKGROUND Hydroxycitric acid is a potential lithontriptic agent for calcium oxalate (CaOx) stones in the kidneys. This study aimed to evaluate the safety and efficiency of hydroxycitric acid tripotassium (K-HCA) against CaOx crystal formation using Drosophila melanogaster hyperoxaluria models. MATERIAL AND METHODS Wild-type D. melanogaster were fed standard medium with ethylene glycol or sodium oxalate added to induce hyperoxaluria. Their Malpighian tubules were dissected and observed under a microscope every 3 days. Crystal deposit score of each Malpighian tubule were evaluated under a magnification of ×200. Using hyperoxaluria Drosophila models, we investigated the inhibitory efficiency of hydroxycitrate acid tripotassium and citric acid tripotassium (K-CA) against CaOx crystal formation. The survival rate of each group was also assessed. RESULTS When fed with 0.05% NaOx, the CaOx formation in Malpighian tubules increased significantly, without reduction of life span. Therefore, we selected 0.05% NaOx-induced hyperoxaluria models for the further investigations. After treatment, the stone scores showed that K-CA and K-HCA both significantly inhibit the formation of CaOx crystals in a dose-dependent manner, and with smaller dosage (0.01%), K-HCA was more efficient than K-CA. Moreover, after treatment of K-CA or K-HCA, the life span in different groups did not change, reflecting the safety to life. CONCLUSIONS The hyperoxaluria Drosophila models fed on 0.05% NaOx diet might be a useful tool to screen novel agents for the management of CaOx stones. K-HCA may be a promising agent for the prevention CaOx stones, with satisfying efficiency and acceptable safety.
羟基柠檬酸是一种潜在的肾结石治疗药物,可用于治疗肾脏中的草酸钙(CaOx)结石。本研究旨在利用黑腹果蝇高草酸尿症模型评估羟基柠檬酸三钾(K-HCA)对 CaOx 晶体形成的安全性和有效性。
将野生型黑腹果蝇喂食含乙二醇或草酸钠的标准培养基,以诱导高草酸尿症。每隔 3 天解剖其马氏管并在显微镜下观察。在 200 倍放大倍数下评估每个马氏管的晶体沉积物评分。利用高草酸尿症果蝇模型,研究了羟基柠檬酸三钾和柠檬酸三钾(K-CA)对 CaOx 晶体形成的抑制效率。还评估了每组的存活率。
当喂食 0.05% NaOx 时,马氏管中的 CaOx 形成显著增加,但寿命没有缩短。因此,我们选择 0.05% NaOx 诱导的高草酸尿症模型进行进一步研究。治疗后,结石评分显示 K-CA 和 K-HCA 均能以剂量依赖性方式显著抑制 CaOx 晶体的形成,且低剂量(0.01%)时,K-HCA 比 K-CA 更有效。此外,在 K-CA 或 K-HCA 处理后,不同组的寿命没有变化,反映了对生命的安全性。
喂食 0.05% NaOx 饮食的高草酸尿症果蝇模型可能是筛选用于治疗 CaOx 结石的新型药物的有用工具。K-HCA 可能是预防 CaOx 结石的一种有前途的药物,具有令人满意的疗效和可接受的安全性。