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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. [ABSTRACT FROM AUTHOR]

Highly transparent, flexible and conductive networks of carbon nanotubes-silver nanowire networks were formed on polyethylene terephthalate (PET) substrates. The high temperature and humidity tests reveal that our CNT-AgNW composite networks maintain high durability and reliability in the electrical and optical properties under high temperature (85 °C) and relative humidity (85% R.H.). When bent and flexed over 1000 cycles; the films did not show significant degradation in sheet resistance compared to Ag films and ITOs on the same flexible substrates; demonstrating the superior mechanical stability of our CNT-AgNWs networks. The composite films on PET were employed for supercapacitor electrodes. The supercapacitors demonstrate a mass specific capacitance of 143 Fg−1 with a stable charge-discharge (3000 cycles) and low internal resistance (16 Ω). Furthermore; the supercapacitors showed high durability under harsh climatic conditions and mechanical bending. Our works indicate that the CNT-AgNWs could be promising transparent conductive electrodes for the applications in flexible optoelectronics and energy storage devices. [ABSTRACT FROM AUTHOR]