Dexmedetomidine improves septic acute kidney injury by inhibiting inflammation and oxidative stress through the activation of the Pink1/Park2 autophagy pathway.

Abstract

Impaired autophagy is a key factor in the development of septic acute kidney injury (SAKI). Dexmedetomidine-an α₂ adrenergic agonist widely used as a sedative-exerts protective effects in SAKI. However, its correlation with autophagy remains unclear. Consequently, this study aimed to investigate whether the protective effect of dexmedetomidine against SAKI is related to the Pink1/Park2 autophagy pathway. Dexmedetomidine was intraperitonally administered to mice before inducing SAKI with lipopolysaccharide. Subsequently, kidney structure, inflammatory markers, renal function, oxidative stress levels, mitochondrial 16S rRNA expression, autophagy-related protein levels (Pink1, Park2, and Optineurin), and renal cell apoptosis rates were evaluated. Dexmedetomidine reduced inflammatory factors, such as tumor necrosis factor-α, interleukin (IL)-18, IL-6, and IL-1β, and improved kidney function by decreasing serum cystatin C, creatinine, blood urea nitrogen, kidney injury molecule-1, and neutrophil gelatinase-associated lipocalin. Furthermore, it also alleviated kidney tissue damage. Additionally, dexmedetomidine enhanced mitochondrial function; reduced kidney tissue levels of reactive oxygen species, catalase, malondialdehyde, and glutathione; increased superoxide dismutase activity; upregulated mt16S expression; promoted the expression of autophagy-related proteins (Pink1, Park2, and Optineurin); and reduced renal cell apoptosis rates. Notably, all results were statistically significant. Overall, our findings revealed that dexmedetomidine may mitigate inflammation, oxidative stress, and renal dysfunction in mice with SAKI by upregulating the Pink1/Park2-mediated autophagy pathway. These preliminary findings highlight dexmedetomidine's potential role in SAKI management and warrant further validation in large scale studies.