Jang Kyu Won, Kim Young Suk, Kim Min Jeong, Kim Seo Rin, Lee Dong Won, Lee Soo Bong, Kim Il Young
Department of Internal Medicine, Pusan National University School of Medicine, Yangsan, Republic of Korea.
Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea.
Kidney Res Clin Pract. 2024 Jul;43(4):444-456. doi: 10.23876/j.krcp.23.351. Epub 2024 Jun 5.
Time-restricted feeding (TRF), devoid of calorie restriction, is acknowledged for promoting metabolic health and mitigating various chronic metabolic diseases. While TRF exhibits widespread benefits across multiple tissues, there is limited exploration into its impact on kidney function. In this study, our aim was to investigate the potential ameliorative effects of TRF on kidney damage in a mouse model of cisplatin-induced acute kidney injury (AKI).
Cisplatin-induced AKI was induced through intraperitoneal injection of cisplatin into C57BL/6 male mice. Mice undergoing TRF were provided unrestricted access to standard chow daily but were confined to an 8-hour feeding window during the dark cycle for 2 weeks before cisplatin injection. The mice were categorized into four groups: control, TRF, cisplatin, and TRF + cisplatin.
The tubular damage score and serum creatinine levels were significantly lower in the TRF + cisplatin group compared to the cisplatin group. The TRF + cisplatin group exhibited reduced expression of phosphorylated nuclear factor kappa B, inflammatory cytokines, and F4/80-positive macrophages compared to the cisplatin group. Furthermore, oxidative stress markers for DNA, protein, and lipid were markedly decreased in the TRF + cisplatin group compared to the cisplatin group. TUNEL-positive tubular cells, cleaved caspase-3 expression, and the Bax/Bcl-2 ratio in the TRF + cisplatin group were lower than those in the cisplatin group.
TRF, without calorie restriction, effectively mitigated kidney damage by suppressing inflammatory reactions, oxidative stress, and tubular apoptosis in a mouse model of cisplatin-induced AKI. TRF holds promise as a novel dietary intervention for preventing cisplatin-induced AKI.
限时进食（TRF），即不进行热量限制，因能促进代谢健康并减轻各种慢性代谢性疾病而得到认可。虽然TRF在多个组织中都显示出广泛的益处，但对其对肾功能影响的研究却很有限。在本研究中，我们的目的是探讨TRF对顺铂诱导的急性肾损伤（AKI）小鼠模型肾损伤的潜在改善作用。
通过向C57BL/6雄性小鼠腹腔注射顺铂诱导顺铂诱导的AKI。接受TRF的小鼠每天可无限制地获取标准食物，但在注射顺铂前2周的黑暗周期内被限制在8小时的进食窗口。小鼠被分为四组：对照组、TRF组、顺铂组和TRF +顺铂组。
与顺铂组相比，TRF +顺铂组的肾小管损伤评分和血清肌酐水平显著降低。与顺铂组相比，TRF +顺铂组磷酸化核因子κB、炎性细胞因子和F4/80阳性巨噬细胞的表达降低。此外，与顺铂组相比，TRF +顺铂组DNA、蛋白质和脂质的氧化应激标志物明显减少。TRF +顺铂组TUNEL阳性肾小管细胞、裂解的半胱天冬酶-3表达和Bax/Bcl-2比值均低于顺铂组。
在顺铂诱导的AKI小鼠模型中，不进行热量限制的TRF通过抑制炎症反应、氧化应激和肾小管凋亡有效地减轻了肾损伤。TRF有望成为预防顺铂诱导的AKI的一种新型饮食干预措施。
