Honeysuckle-Derived Exosome-Like Nanovesicles Alleviate Cisplatin-Induced Acute Kidney Injury by Anti-Inflammation and Mitochondrial Function Protection

Objective: To explore the potential of honeysuckle-derived exosome-like nanovesicles (HELNVs) for preventing cisplatin-induced acute kidney injury (AKI).

Methods: The renoprotective efficacy of HELNVs against cisplatin-induced AKI was assessed in human kidney cell-2 (HK-2) cells exposed to 100 μmol/L cisplatin for 24 h, followed by HELNVs (50-200 μg/mL) for another 24 h; the optimal therapeutic concentration was determined as 100 μg/mL. At this concentration, oxygen species (ROS) levels were measured by flow cytometry. Male C57BL/6 mice received a single intraperitoneal injection of cisplatin (30 mg/kg) to establish an AKI model and were then computer-randomized into 3 groups (n=6 per group): control group, daily intraperitoneal administration of normal saline (0.9% NaCl); the cisplatin-injured group, same NaCl regimen; the HELNVs treatment group, daily intraperitoneal administration of HELNVs (30 mg/kg) for 5 consecutive days, with euthanasia on day 6. Renal accumulation of HELNVs was tracked by small-animal multispectral imaging (peak uptake at 8-10 h). Functional assessment included serum creatinine and blood urea nitrogen (BUN) quantified with an automated biochemical analyzer. Molecular analyses included enzyme-linked immunosorbent assay (ELISA) quantification of interleukin (IL)-1β, IL-6, IL-10, and tumor necrosis factor-α (TNF-α).

Results: HELNVs significantly reduced ROS, inflammatory responses, and Apoptosis in cisplatin-treated HK-2 cells (P<0.01). In cisplatin-induced AKI mice, HELNVs were efficiently absorbed by kidney cells, effectively prevented oxidative damage and mitochondrial dysfunction (P<0.01). Following treatment with 30 mg/kg HELNVs, serum creatinine and BUN levels were markedly reduced (P<0.01). ELISA results showed decreased levels of IL-1β, IL-6, and TNF-α, along with up-regulated IL-10 (P<0.01).

Conclusion: HELNVs may serve as a promising therapeutic approach for ameliorating cisplatin-induced AKI, offering a potential novel treatment option for managing this condition in clinical settings.

anti-apoptosis; antiinflammation; cisplatin-induced acute kidney injury; honeysuckle-derived exosome-like nanovesicles; mitochondrial function protection.