Objective. To investigate the role of inflammatory reactions and oxidative stress injury in the mechanisms of ceftriaxone calcium crystal-induced acute kidney injury (AKI) both in vivo and in vitro. Methods. Male Sprague Dawley rats were randomly divided into five groups of ten each according to different concentrations of ceftriaxone and calcium. Based on the levels of serum creatinine (Scr) and blood urea nitrogen (BUN), the AKI group was chosen for the subsequent experiments. Kidney histological examination and immunohistochemistry were performed. The expression of NLRP3 and IL-1β protein and the concentrations of oxidative stress markers such as ROS, MDA, and H₂O₂ in kidney tissues were estimated. In parallel, HK-2 human renal proximal tubule cells were exposed to ceftriaxone calcium crystals. The mRNA expression levels of NLRP3 and IL-1β and the concentrations of oxidative stress markers were evaluated. Finally, cell viability and rat survival were also assessed. Results. The results showed that significantly increased Scr and BUN levels, consistent with morphological changes and kidney stones, were found in the rats that received the highest concentration of ceftriaxone (1000 mg/kg) combined with calcium (800 mg/kg). The activation of the NLRP3 inflammasome axis and the marked elevation of MDA, H₂O₂, and ROS levels were observed both in vivo and in vitro. High expression of Nrf2, HO-1, and NQO1 was also documented. In addition, cell apoptosis and rat mortality were promoted by ceftriaxone calcium crystals. Conclusions. Notably, we found that ceftriaxone-induced urolithiasis was associated with a high risk of AKI and NLRP3-mediated inflammasome and oxidative stress injury were of major importance in the pathogenesis.

中文翻译：

---

头孢曲松钙晶体通过 NLRP3 介导的炎症和氧化应激损伤诱导急性肾损伤。

客观。探讨炎症反应和氧化应激损伤在头孢曲松钙晶体致急性肾损伤（AKI）的体内外机制中的作用。方法。雄性Sprague Dawley大鼠根据头孢曲松和钙的不同浓度随机分为5组，每组10只。根据血清肌酐（Scr）和血尿素氮（BUN）水平，选择AKI组进行后续实验。进行肾脏组织学检查和免疫组织化学检查。NLRP3、IL- 1β蛋白的表达及ROS、MDA、H ₂ O _{2等氧化应激标志物的浓度}估计在肾组织中。同时，将 HK-2 人肾近端小管细胞暴露于头孢曲松钙晶体。评估NLRP3和IL- 1β的mRNA表达水平以及氧化应激标志物的浓度。最后，还评估了细胞活力和大鼠存活率。结果。结果表明，在接受最高浓度的头孢曲松（1000 mg/kg）联合钙（800 mg/kg）的大鼠中，Scr 和 BUN 水平显着增加，与形态变化和肾结石一致。NLRP3炎性体轴的激活和MDA、H ₂ O _{2的显着升高}, 并且在体内和体外均观察到 ROS 水平。还记录了 Nrf2、HO-1 和 NQO1 的高表达。此外，头孢曲松钙晶体可促进细胞凋亡和大鼠死亡率。结论。值得注意的是，我们发现头孢曲松诱导的尿石症与 AKI 的高风险相关，NLRP3 介导的炎性体和氧化应激损伤在发病机制中具有重要意义。