Institute of Biomineralization and Lithiasis Research, College of Chemistry and Materials Science, Jinan University, Guangzhou 510632, China.
Biomolecules. 2023 Jun 27;13(7):1044. doi: 10.3390/biom13071044.
This study explored the effects of polysaccharides (RAPD) extracted from the traditional anti-stone Chinese medicine and their carboxymethylated derivatives (RAPs) on the crystal phase, morphology, and size of calcium oxalate (CaOx). It also determined the damaging ability of the regulated crystals on human renal tubular epithelial cells (HK-2).
RAPD carboxymethylation with a carboxyl group (-COOH) content of 3.57% was carried out by the chloroacetic acid solvent method. The effects of -COOH content in RAPs and RAP concentration on the regulation of CaOx crystal growth were studied by controlling the variables. Cell experiments were conducted to explore the differences in the cytotoxicity of RAP-regulated crystals.
The -COOH contents of RAPD, RAP1, RAP2, and RAP3 were 3.57%, 7.79%, 10.84%, and 15.33%, respectively. RAPs can inhibit the growth of calcium oxalate monohydrate (COM) and induce the formation of calcium oxalate dihydrate (COD). When the -COOH content in RAPs was high, their ability to induce COD formation was enhanced. In the crystals induced by RAPs, a high COD content can lower the damage to cells. In particular, the cytotoxicity of the crystals induced by RAP3 was the lowest. When the concentration of RAP3 increased, the cytotoxicity gradually increased due to the reduced size of the formed COD crystals. An interaction was observed between RAPs and crystals, and the number of RAPs adsorbed in the crystals was positively correlated with the -COOH content in RAPs.
RAPs can reduce the damage of CaOx to HK-2 cells by regulating the crystallization of CaOx crystals and effectively reducing the risk of kidney stone formation. RAPs, especially RAP3 with a high carboxyl group content, has the potential to be developed as a novel green anti-stone drug.
本研究探讨了从传统抗石中药中提取的多糖（RAPD）及其羧甲基化衍生物（RAPs）对草酸钙（CaOx）晶体相、形态和大小的影响。还测定了调节晶体对人肾小管上皮细胞（HK-2）的损伤能力。
采用氯乙酸溶剂法对 RAPD 进行羧甲基化，羧基（-COOH）含量为 3.57%。通过控制变量研究 RAPs 中的 -COOH 含量和 RAP 浓度对调节 CaOx 晶体生长的影响。进行细胞实验以探讨 RAP 调节晶体的细胞毒性差异。
RAPD、RAP1、RAP2 和 RAP3 的 -COOH 含量分别为 3.57%、7.79%、10.84%和 15.33%。RAPs 可以抑制一水合草酸钙（COM）的生长并诱导二水合草酸钙（COD）的形成。当 RAPs 中的 -COOH 含量较高时，其诱导 COD 形成的能力增强。在 RAPs 诱导的晶体中，高 COD 含量可以降低对细胞的损伤。特别是 RAP3 诱导的晶体毒性最低。随着 RAP3 浓度的增加，由于形成的 COD 晶体尺寸减小，细胞毒性逐渐增加。观察到 RAPs 与晶体之间存在相互作用，吸附在晶体中的 RAPs 数量与 RAPs 中的 -COOH 含量呈正相关。
RAPs 可以通过调节 CaOx 晶体的结晶来降低 CaOx 对 HK-2 细胞的损伤，并有效降低肾结石形成的风险。RAPs，特别是高羧基含量的 RAP3，具有开发新型绿色抗石药物的潜力。
