Dimethyl fumarate ameliorates oxidative stress-induced acute kidney injury after traumatic brain injury by activating Keap1-Nrf2/HO-1 signaling pathway

作者：Mei-zhu Gao, Jing-Yi Zeng, Xue-jing Chen, Shi Lan, Fu‐Yuan Hong, Miao Lin, Jie-wei Luo, Han Chen · 发表于：Heliyon · 年份：2024 · DOI：10.1016/j.heliyon.2024.e32377 · 被引用次数：8 · 研究领域：Acute Kidney Injury Research、Traumatic Brain Injury and Neurovascular Disturbances、Heme Oxygenase-1 and Carbon Monoxide

Acute kidney injury (AKI) frequently emerges as a consequential non-neurological sequel to traumatic brain injury (TBI), significantly contributing to heightened mortality risks. The intricate interplay of oxidative stress in the pathophysiology of TBI underscores the centrality of the Keap1-Nrf2/HO-1 signaling pathway as a pivotal regulator in this context. This study endeavors to elucidate the involvement of the Keap1-Nrf2/HO-1 pathway in modulating oxidative stress in AKI subsequent to TBI and concurrently explore the therapeutic efficacy of dimethyl fumarate (DMF). A rat model of TBI was established via the Feeney free-fall method, incorporating interventions with varying concentrations of DMF. Assessment of renal function ensued through measurements of serum creatinine and neutrophil gelatinase-associated lipocalin. Morphological evaluation of renal pathology was conducted employing quantitative hematoxylin and eosin staining. The inflammatory response was scrutinized by quantifying interleukin (IL)-6, IL-1β, and tumor necrosis factor-α levels. Oxidative stress levels were discerned through quantification of malondialdehyde and superoxide dismutase. The apoptotic cascade was examined via the terminal deoxynucleotidyl transferase dUTP deletion labeling assay. Western blotting provided insights into the expression dynamics of proteins affiliated with the Keap1-Nrf2/HO-1 pathway and apoptosis. The findings revealed severe kidney injury, heightened oxidative stress, inflamma...