Abstract:

Objective To investigate the protective effect and potential mechanism of iridium-doped carbon dot (Ir-CDs) nanozymes on cadmium-induced kidney injury so as to provide a new strategy for intervention against renal damage caused by the heavy metal cadmium.

Methods Ir-CDs were synthesized, and their enzyme-like activity was evaluated. The cytotoxicity of Ir-CDs on HK-2 cells and their reactive oxygen species (ROS) scavenging ability were investigated in vitro. Fifteen mice were randomly divided into five groups (n = 3): control group, Ir-CDs group, Cd group, Cd+CDs group, and Cd+Ir-CDs group.A kidney injury model was established by administering cadmium injections for seven consecutive days. Meanwhile, the corresponding groups (Ir-CDs group and Cd+Ir-CDs group) received Ir-CDs treatment on days 1, 3, 5, and 7. The levels of renal reactive oxygen species (ROS) and renal function indicators including creatinine (CREA), urea (UREA), and uric acid (UA) were measured. The intervention effects were evaluated through renal histopathology using HE staining and DHE staining, as well as routine blood tests and multi-organ tissue examinations. The additional 6 mice were randomly divided into 2 groups (blank control group and 4 mg/kg Ir-CDs group) to assess the biocompatibility and biosafety of the materials.

Results The synthesized CDs and Ir-CDs exhibited a uniform morphology. Ir-CDs had an average diameter of (9.2 ± 3.32) nm. They effectively scavenged hydrogen peroxide (H₂O₂) and hydroxyl radicals (·OH) (P < 0.001). Cell viability results showed that, compared with the control group, there were no statistically significant differences in cell survival rates among the CDs and Ir-CDs groups (all P ≥ 0.05), except for the 40 μg/mL Ir-CDs group, where cell survival rate decreased to 79.88% ± 5.52%. Furthermore, Ir-CDs significantly reduced cadmium-induced intracellular ROS levels (P < 0.05). In animal models, the results of serum renal function tests (CREA, UREA, and UA) in mice showed that, compared with the control group, CREA and UREA levels were both reduced in the Cd group (P < 0.05), while UA levels were elevated (P < 0.05); in the Ir-CDs group, there were no statistically significant differences in the three renal function indicators (all P > 0.05); compared with the Cd group, the CREA and UREA levels in the Cd+Ir-CDs group were increased (both P < 0.01), and UA levels decreased (P < 0.05). Additionally, compared with the normal mice in the control group, there were no statistically significant differences in various hematological indicators in the Ir-CDs group (all P > 0.05). Ir-CDs had good biocompatibility.

Conclusions Ir-CDs significantly protect against cadmium-induced kidney injury by inhibiting oxidative stress, improving renal function, and alleviating tissue damage, with good biocompatibility. This study provides new experimental evidence and a potential strategy for intervention in cadmium-induced renal injury.