트라메티닙（Trametinib）이 시스플라틴（Cisplatin）에 의해 발생한 급성 신손상을 완화하는 기능 : 쥐 연구에서 염증, 산화 스트레스 및 세포사멸 억제 = Efficacy of Trametinib in Alleviating Cisplatin-Induced Acute Kidney Injury: Inhibition of Inflammation, Oxidative Stress, and Tubular Cell Death in a Mouse Model

다국어 초록 (Multilingual Abstract)

Cisplatin, a platinum-based chemotherapeutic, is effective against various solid tumors, but its use is often limited by its nephrotoxic effects. This study evaluated the protective effects of trametinib, an FDA-approved selective inhibitor of mitogen-activated protein kinase kinase 1/2 （MEK1/2）, against cisplatin-induced acute kidney injury （AKI） in mice. The experimental design included four groups, control, trametinib, cisplatin, and a combination of cisplatin and trametinib, each consisting of eight mice. Cisplatin was administered intraperitoneally at a dose of 20 mg/kg to induce kidney injury, while trametinib was administered via oral gavage at 3 mg/kg daily for three days. Assessments were conducted 72 h after cisplatin administration. Our results demonstrate that trametinib significantly reduces the phosphorylation of MEK1/2 and extracellular signal-regulated kinase 1/2 （ERK1/2）, mitigated renal dysfunction, and ameliorated histopathological abnormalities. Additionally, trametinib significantly decreased macrophage infiltration and the expression of pro-inflammatory cytokines in the kidneys. It also lowered lipid peroxidation by-products, restored the reduced glutathione/oxidized glutathione ratio, and downregulated NADPH oxidase 4. Furthermore, trametinib significantly inhibited both apoptosis and necroptosis in the kidneys. In conclusion, our data underscore the potential of trametinib as a therapeutic agent for cisplatin-induced AKI, highlighting its role in reducing inflammation, oxidative stress, and tubular cell death.

목차 (Table of Contents)

• Abstract
• Ⅰ. 서론 1
• Ⅱ. 결과 3
• Ⅲ. 논의 15
• Ⅳ. 재료 및 방법 20
• Ⅴ. 결론 26
• Ⅵ. 참고문헌 27