Myricetin-Loaded Nanomicelles Protect against Cisplatin-Induced Acute Kidney Injury by Inhibiting the DNA Damage-cGAS–STING Signaling Pathway

• DOI: 10.1021/acs.molpharmaceut.2c00520
• Publication Date: 2022-11-03T13:44:17Z
• Authors: Xueju Qi; Jing Wang; Fengshu Fei; Xintao Gao; Xiaochen Wu; Dayong Shi; Chuanlong Guo
• Keywords: Myricetin; myr

Acute kidney injury (AKI) is the most common side effect of anti-cancer drug cisplatin, and currently, no effective preventive measures are available in clinical practice. Oxidative stress DNA damage mechanisms may be involved cisplatin-induced AKI. In this study, we prepared Kolliphor HS15-based myricetin-loaded (HS15-Myr) nanomicelles explored mechanism protection against vitro results showed that HS15-Myr enhanced antioxidant activity myricetin (Myr) inhibited proliferation inhibition HK-2 cells. Moreover, reactive oxygen species accumulation, mitochondrial membrane potential reduction, damage, which might related to cyclic GMP–AMP synthase (cGAS)─stimulating interferon gene (STING) signaling pathway. vivo mice significant reductions body weight renal indices increased blood urea nitrogen serum creatinine levels induced by cisplatin could significantly reversed pretreating with nanomicelles. Furthermore, nanomicelle pretreatment altered activities enzymes (e.g., GSH, MDA, SOD) cisplatin. addition, inflammatory responses mouse tissue were found nanomicelles, such as IL-1β TNF-α expression. The also activation damage-cGAS–STING pathway tissues. Together, our findings suggest Myr-loaded nephroprotective drugs.