Objective:

2

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

Methods:

2

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:

2

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:

2

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.