Cao Pei, Li Yaqian, Zhang Zhiqing
Department of Pharmacy, The Second Hospital of Hebei Medical University, Shijiazhuang, 050051, P. R. China.
Iran J Basic Med Sci. 2024;27(10):1243-1250. doi: 10.22038/ijbms.2024.75089.16343.
Prior research has indicated that hydroxycitric acid (HCA) can impede the formation of calcium oxalate (CaOx) crystals, yet the specific mechanisms underlying its therapeutic effects remain unclear. In this study, we delved into the protective effects of HCA against glyoxylate-induced renal stones in rats and sought to elucidate the underlying metabolic pathways.
Forty rats were randomly assigned to five groups: control group, model group, L-HCA-treated group, M-HCA-treated group, and H-HCA-treated group. Von Kossa staining was conducted on renal sections, and blood urea nitrogen and serum creatinine were determined by biochemical analysis. Meanwhile, body weight and urine volume were also measured. We subjected urine samples from the rats to analysis using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Next, we employed a metabolomic approach to scrutinize the metabolic profiles of each group.
HCA significantly reduced blood urea nitrogen and serum creatinine, and increased body weight and urine volume. It also reduced CaOx crystal deposition. A total of 24 metabolites, exhibiting a significant reversal pattern following HCA administration, were identified as urine biomarkers indicative of HCA's preventive effects against CaOx crystal-induced renal injury. These metabolites are primarily associated with glycine, serine, and threonine metabolism; phenylalanine metabolism; tricarboxylic acid cycle; taurine and hypotaurine metabolism; and tryptophan metabolism.
It was demonstrated that HCA has a protective effect against CaOx crystal-induced kidney injury in rats by modulating various metabolic pathways. Additionally, results suggest that HCA holds promise as a potential clinical therapeutic drug for both the prevention and treatment of renal stones.
先前的研究表明,羟基柠檬酸(HCA)可阻碍草酸钙(CaOx)晶体的形成,但其治疗效果的具体机制仍不清楚。在本研究中,我们深入探讨了HCA对乙醛酸诱导的大鼠肾结石的保护作用,并试图阐明其潜在的代谢途径。
将40只大鼠随机分为五组:对照组、模型组、低剂量HCA治疗组、中剂量HCA治疗组和高剂量HCA治疗组。对肾脏切片进行冯·科萨染色,并通过生化分析测定血尿素氮和血清肌酐。同时,还测量了体重和尿量。我们使用超高效液相色谱-四极杆飞行时间质谱对大鼠的尿液样本进行分析。接下来,我们采用代谢组学方法来仔细研究每组的代谢谱。
HCA显著降低了血尿素氮和血清肌酐,并增加了体重和尿量。它还减少了CaOx晶体沉积。共鉴定出24种代谢物,在给予HCA后呈现出显著的逆转模式,这些代谢物被确定为尿液生物标志物,表明HCA对CaOx晶体诱导的肾损伤具有预防作用。这些代谢物主要与甘氨酸、丝氨酸和苏氨酸代谢;苯丙氨酸代谢;三羧酸循环;牛磺酸和亚牛磺酸代谢;以及色氨酸代谢有关。
结果表明,HCA通过调节多种代谢途径对CaOx晶体诱导的大鼠肾损伤具有保护作用。此外,结果表明HCA有望成为预防和治疗肾结石的潜在临床治疗药物。