摘要
Itch（pruritus） is one of the most disabling syndromes in patients suffering from skin, liver, or kidney diseases. Our previous study highlighted a key role of oxidative stress in acute itch. Here, we evaluated the effects of antioxidants in mouse models of acute and chronic itch and explored the potential mechanisms. The effects of systemic administration of the antioxidants N-acetyl-Lcysteine（NAC） and N-tert-butyl-a-phenylnitrone（PBN）were determined by behavioral tests in mouse models of acute itch induced by compound 48/80 or chloroquine, and chronic itch by treatment with a mixture of acetonediethyl-ether-water. We found that systemic administration of NAC or PBN significantly alleviated compound 48/80-and chloroquine-induced acute itch in a dose-dependent manner, attenuated dry skin-induced chronic itch, and suppressed oxidative stress in the affected skin.Antioxidants significantly decreased the accumulation of intracellular reactive oxygen species directly induced by compound 48/80 and chloroquine in the cultured dorsal root ganglia-derived cell line ND7-23. Finally, the antioxidants remarkably inhibited the compound 48/80-induced phosphorylation of extracellular signal-regulated kinase in the spinal cord. These results indicated that oxidative stress plays a critical role in acute and chronic itch in the periphery and spinal cord and antioxidant treatment may be a promising strategy for anti-itch therapy.
Itch（pruritus） is one of the most disabling syndromes in patients suffering from skin, liver, or kidney diseases. Our previous study highlighted a key role of oxidative stress in acute itch. Here, we evaluated the effects of antioxidants in mouse models of acute and chronic itch and explored the potential mechanisms. The effects of systemic administration of the antioxidants N-acetyl-Lcysteine（NAC） and N-tert-butyl-a-phenylnitrone（PBN）were determined by behavioral tests in mouse models of acute itch induced by compound 48/80 or chloroquine, and chronic itch by treatment with a mixture of acetonediethyl-ether-water. We found that systemic administration of NAC or PBN significantly alleviated compound 48/80-and chloroquine-induced acute itch in a dose-dependent manner, attenuated dry skin-induced chronic itch, and suppressed oxidative stress in the affected skin.Antioxidants significantly decreased the accumulation of intracellular reactive oxygen species directly induced by compound 48/80 and chloroquine in the cultured dorsal root ganglia-derived cell line ND7-23. Finally, the antioxidants remarkably inhibited the compound 48/80-induced phosphorylation of extracellular signal-regulated kinase in the spinal cord. These results indicated that oxidative stress plays a critical role in acute and chronic itch in the periphery and spinal cord and antioxidant treatment may be a promising strategy for anti-itch therapy.
基金
supported by grants from the National Natural Science Foundation of China(31371179 and 81300968)
the Natural Science Foundation of Jiangsu Province,China(BK20140372)
supported by funding from Jiangsu Province,China(2015-JY-029)
supported by a grant from Jiangsu Province,China(201310285096X)
subject to the second affiliated hospital of Soochow University Preponderant Clinic Discipline Group Project Funding(XKQ2015007)
a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions
