Abstract
Cu-Zn superoxide dismutase (Sod1) loss causes a redox imbalance as it leads to excess superoxide generation, which results in the appearance of various aging-related phenotypes, including skin atrophy. Noble metal nanoparticles, such as palladium (Pd) and platinum (Pt) nanoparticles, are considered to function as antioxidants due to their strong catalytic activity. In Japan, a mixture of Pd and Pt nanoparticles called PAPLAL has been used to treat chronic diseases over the past 60 years. In the present study, we investigated the protective effects of PAPLAL against aging-related skin pathologies in mice. Transdermal PAPLAL treatment reversed skin thinning associated with increased lipid peroxidation in Sod1 −/− mice. Furthermore, PAPLAL normalized the gene expression levels of Col1a1, Mmp2, Has2, Tnf-α, Il-6, and p53 in the skin of the Sod1 −/− mice. Pt nanoparticles exhibited marked SOD and catalase activity, while Pd nanoparticles only displayed weak SOD and catalase activity in vitro. Although the SOD and catalase activity of the Pt nanoparticles significantly declined after they had been oxidized in air, a mixture of Pd and Pt nanoparticles continued to exhibit SOD and catalase activity after oxidation. Importantly, a mixture of Pd and Pt nanoparticles with a molar ratio of 3 or 4 to 1 continued to exhibit SOD and catalase activity after oxidation, indicating that Pd nanoparticles prevent the oxidative deterioration of Pt nanoparticles. These findings indicate that PAPLAL stably suppresses intrinsic superoxide generation both in vivo and in vitro via SOD and catalase activity. PAPLAL is a potentially powerful tool for the treatment of aging-related skin diseases caused by oxidative damage.
Highlights
Skin aging induced by chronological or intrinsic factors leads to skin atrophy [1]
In order to investigate the beneficial effects of PAPLAL on the skin symptoms seen in Sod12/2 mice, PAPLAL was transdermally administered to the skin on the backs of Sod12/2 and wild-type (Sod1+/+) mice daily for four weeks, beginning at four months of age
The administration of a low concentration of PAPLAL improved the skin atrophy observed in the Sod12/2 mice compared with that seen in the Sod12/2 mice treated with vehicle
Summary
Skin aging induced by chronological or intrinsic factors leads to skin atrophy [1]. The amounts of skin collagen components fall in an age-dependent manner in both males and females, resulting in age-related skin thinning in older individuals [2,3]. Evidence suggests that oxidatively modified proteins, DNA, and lipids in the skin and other organs progressively accumulate during aging [4], indicating that reactive oxygen species (ROS) are strongly associated with skin aging. Complex organisms possess multiple antioxidative and repair systems for mitigating oxidative damage. Superoxide dismutase (SOD) plays a central role in antioxidative systems due to its ability to catalyze the conversion of cellular superoxide (O22) to hydrogen peroxide (H2O2). Copper/zinc superoxide dismutase (SOD1) is localized to react with intracellular O2 in the cytoplasm. Our previous studies have demonstrated that Sod1-deficient (Sod12/2)
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