Molecular hydrogen reduces dermatitis-induced itch, diabetic itch and cholestatic itch by inhibiting spinal oxidative stress and synaptic plasticity via SIRT1-β-catenin pathway in mice
Chronic itch which is primarily associated with dermatologic, systemic, or metabolic disorders is often refractory to most current antipruritic medications, thus highlighting the need for improved therapies. Oxidative damage is a novel determinant of spinal pruriceptive sensitization and synaptic pl...
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Elsevier
2025-02-01
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| Series: | Redox Biology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231724004506 |
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| author | Linlin Zhang Fangshi Zhao Yize Li Zhenhua Song Lingyue Hu Yuanjie Li Rui Zhang Yonghao Yu Guolin Wang Chunyan Wang |
| author_facet | Linlin Zhang Fangshi Zhao Yize Li Zhenhua Song Lingyue Hu Yuanjie Li Rui Zhang Yonghao Yu Guolin Wang Chunyan Wang |
| author_sort | Linlin Zhang |
| collection | DOAJ |
| description | Chronic itch which is primarily associated with dermatologic, systemic, or metabolic disorders is often refractory to most current antipruritic medications, thus highlighting the need for improved therapies. Oxidative damage is a novel determinant of spinal pruriceptive sensitization and synaptic plasticity. The resolution of oxidative insult by molecular hydrogen has been manifested. Herein, we strikingly report that both hydrogen gas (2 %) inhalation and hydrogen-rich saline (5 mL/kg, intraperitoneal) injection prevent and alleviate persistent dermatitis-induced itch, diabetic itch and cholestatic itch. Hydrogen therapy reverses the decrease of spinal SIRT1 expression and antioxidant enzymes (SOD, GPx and CAT) activity after dermatitis, diabetes and cholestasis. Furthermore, hydrogen reduces spinal ROS generation, oxidation products (MDA, 8-OHdG and 3-NT) accumulation, β-catenin acetylation and dendritic spine density in persistent itch models. Spinal SIRT1 inhibition eliminates antipruritic and antioxidative effects of hydrogen, while SIRT1 agonism attenuates chronic itch phenotype, spinal β-catenin acetylation and mitochondrial damage. β-catenin inhibitors are effective against chronic itch via reducing β-catenin acetylation, blocking ERK phosphorylation and elevating antioxidant enzymes activity. Hydrogen treatment suppressed dermatitis and cholestasis mediated spontaneous excitatory postsynaptic currents in vitro. Additionally, hydrogen impairs cholestasis-induced the enhancement of cerebral functional connectivity between the right primary cingulate cortex and bilateral sensorimotor cortex, as well as bilateral striatum. Taken together, this study uncovers that molecular hydrogen protects against chronic pruritus and spinal pruriceptive sensitization by reducing oxidative damage via up-regulation of SIRT1-dependent β-catenin deacetylation in mice, implying a promising strategy in translational development for itch control. |
| format | Article |
| id | doaj-art-220b31aca4ed437d963ad4f937e76fb7 |
| institution | Kabale University |
| issn | 2213-2317 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj-art-220b31aca4ed437d963ad4f937e76fb72025-01-14T04:12:11ZengElsevierRedox Biology2213-23172025-02-0179103472Molecular hydrogen reduces dermatitis-induced itch, diabetic itch and cholestatic itch by inhibiting spinal oxidative stress and synaptic plasticity via SIRT1-β-catenin pathway in miceLinlin Zhang0Fangshi Zhao1Yize Li2Zhenhua Song3Lingyue Hu4Yuanjie Li5Rui Zhang6Yonghao Yu7Guolin Wang8Chunyan Wang9Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin, 300052, China; Tianjin Research Institute of Anesthesiology, Tianjin, 300052, China; Corresponding author. Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin, 300052, China.Department of Radiology and Tianjin Key Laboratory of Functional Imaging and Tianjin Institute of Radiology, Department of Medical Imaging, Tianjin Medical University General Hospital, Tianjin, 300052, ChinaDepartment of Anesthesiology, Tianjin Medical University General Hospital, Tianjin, 300052, China; Tianjin Research Institute of Anesthesiology, Tianjin, 300052, ChinaDepartment of Anesthesiology, Tianjin Medical University General Hospital, Tianjin, 300052, China; Tianjin Research Institute of Anesthesiology, Tianjin, 300052, ChinaDepartment of Anesthesiology, Tianjin Medical University General Hospital, Tianjin, 300052, China; Tianjin Research Institute of Anesthesiology, Tianjin, 300052, ChinaDepartment of Anesthesiology, Tianjin Medical University General Hospital, Tianjin, 300052, China; Tianjin Research Institute of Anesthesiology, Tianjin, 300052, ChinaDepartment of Anesthesiology, Tianjin Medical University General Hospital, Tianjin, 300052, China; Tianjin Research Institute of Anesthesiology, Tianjin, 300052, ChinaDepartment of Anesthesiology, Tianjin Medical University General Hospital, Tianjin, 300052, China; Tianjin Research Institute of Anesthesiology, Tianjin, 300052, ChinaDepartment of Anesthesiology, Tianjin Medical University General Hospital, Tianjin, 300052, China; Tianjin Research Institute of Anesthesiology, Tianjin, 300052, ChinaDepartment of Anesthesiology, Tianjin Medical University General Hospital, Tianjin, 300052, China; Tianjin Research Institute of Anesthesiology, Tianjin, 300052, China; Corresponding author. Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin, 300052, China.Chronic itch which is primarily associated with dermatologic, systemic, or metabolic disorders is often refractory to most current antipruritic medications, thus highlighting the need for improved therapies. Oxidative damage is a novel determinant of spinal pruriceptive sensitization and synaptic plasticity. The resolution of oxidative insult by molecular hydrogen has been manifested. Herein, we strikingly report that both hydrogen gas (2 %) inhalation and hydrogen-rich saline (5 mL/kg, intraperitoneal) injection prevent and alleviate persistent dermatitis-induced itch, diabetic itch and cholestatic itch. Hydrogen therapy reverses the decrease of spinal SIRT1 expression and antioxidant enzymes (SOD, GPx and CAT) activity after dermatitis, diabetes and cholestasis. Furthermore, hydrogen reduces spinal ROS generation, oxidation products (MDA, 8-OHdG and 3-NT) accumulation, β-catenin acetylation and dendritic spine density in persistent itch models. Spinal SIRT1 inhibition eliminates antipruritic and antioxidative effects of hydrogen, while SIRT1 agonism attenuates chronic itch phenotype, spinal β-catenin acetylation and mitochondrial damage. β-catenin inhibitors are effective against chronic itch via reducing β-catenin acetylation, blocking ERK phosphorylation and elevating antioxidant enzymes activity. Hydrogen treatment suppressed dermatitis and cholestasis mediated spontaneous excitatory postsynaptic currents in vitro. Additionally, hydrogen impairs cholestasis-induced the enhancement of cerebral functional connectivity between the right primary cingulate cortex and bilateral sensorimotor cortex, as well as bilateral striatum. Taken together, this study uncovers that molecular hydrogen protects against chronic pruritus and spinal pruriceptive sensitization by reducing oxidative damage via up-regulation of SIRT1-dependent β-catenin deacetylation in mice, implying a promising strategy in translational development for itch control.http://www.sciencedirect.com/science/article/pii/S2213231724004506β-cateninChronic itchHydrogenOxidative stressSIRT1Synaptic plasticity |
| spellingShingle | Linlin Zhang Fangshi Zhao Yize Li Zhenhua Song Lingyue Hu Yuanjie Li Rui Zhang Yonghao Yu Guolin Wang Chunyan Wang Molecular hydrogen reduces dermatitis-induced itch, diabetic itch and cholestatic itch by inhibiting spinal oxidative stress and synaptic plasticity via SIRT1-β-catenin pathway in mice Redox Biology β-catenin Chronic itch Hydrogen Oxidative stress SIRT1 Synaptic plasticity |
| title | Molecular hydrogen reduces dermatitis-induced itch, diabetic itch and cholestatic itch by inhibiting spinal oxidative stress and synaptic plasticity via SIRT1-β-catenin pathway in mice |
| title_full | Molecular hydrogen reduces dermatitis-induced itch, diabetic itch and cholestatic itch by inhibiting spinal oxidative stress and synaptic plasticity via SIRT1-β-catenin pathway in mice |
| title_fullStr | Molecular hydrogen reduces dermatitis-induced itch, diabetic itch and cholestatic itch by inhibiting spinal oxidative stress and synaptic plasticity via SIRT1-β-catenin pathway in mice |
| title_full_unstemmed | Molecular hydrogen reduces dermatitis-induced itch, diabetic itch and cholestatic itch by inhibiting spinal oxidative stress and synaptic plasticity via SIRT1-β-catenin pathway in mice |
| title_short | Molecular hydrogen reduces dermatitis-induced itch, diabetic itch and cholestatic itch by inhibiting spinal oxidative stress and synaptic plasticity via SIRT1-β-catenin pathway in mice |
| title_sort | molecular hydrogen reduces dermatitis induced itch diabetic itch and cholestatic itch by inhibiting spinal oxidative stress and synaptic plasticity via sirt1 β catenin pathway in mice |
| topic | β-catenin Chronic itch Hydrogen Oxidative stress SIRT1 Synaptic plasticity |
| url | http://www.sciencedirect.com/science/article/pii/S2213231724004506 |
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