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15.07.2023 | Sleep Breathing Physiology and Disorders • Original Article

Intermittent hypoxia induces hepatic senescence through promoting oxidative stress in a mouse model

verfasst von: Yayong Li, Yuanguo Chen, Jingjie Kuang, Silei Deng, Yina Wang

Erschienen in: Sleep and Breathing | Ausgabe 1/2024

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Abstract

Purpose

Metabolic-associated fatty liver disease (MAFLD) is an aging-related disease. Obstructive sleep apnea (OSA) may cause MAFLD. This study aimed to explore whether or not intermittent hypoxia (IH), the hallmark of OSA, induces liver aging through oxidative stress.

Methods

C57BL/6J male mice were administered normal air (control), IH, or antioxidant tempol + IH daily for 6 weeks before the collection of serum and liver tissue samples. A histological examination was conducted to assess liver aging. ELISA was performed to measure liver function indicator levels in the serum and oxidative stress indicator activities in the liver. Western blot analysis was carried out to determine the protein expression of the markers related to oxidative stress, inflammation, and senescence.

Results

Compared with control, IH resulted in significant increases in serum ALT, AST, and TG levels in mice (all P < 0.001), along with lobular inflammation and accumulation of collagen and fat in the liver. The protein levels of inflammatory factors and senescent markers were significantly increased in the IH mouse liver compared with those in the control mouse liver. Meanwhile, IH significantly reduced SOD and CAT activities while enhancing p22^phox and Nrf2 protein expression in mouse liver compared with control. Importantly, antioxidant therapy with tempol effectively abrogated the effects of IH on oxidative stress response and aging-related liver injury.

Conclusions

Our findings suggest that IH induces liver inflammation and aging through oxidative stress. OSA may exacerbate target organ aging and participate in target organ damage. Strategies targeting oxidative stress may prevent and treat OSA-related MAFLD.

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Titel: Intermittent hypoxia induces hepatic senescence through promoting oxidative stress in a mouse model
verfasst von: Yayong Li
Yuanguo Chen
Jingjie Kuang
Silei Deng
Yina Wang
Publikationsdatum: 15.07.2023
Verlag: Springer International Publishing
Erschienen in: Sleep and Breathing / Ausgabe 1/2024
Print ISSN: 1520-9512
Elektronische ISSN: 1522-1709
DOI: https://doi.org/10.1007/s11325-023-02878-1

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Intermittent hypoxia induces hepatic senescence through promoting oxidative stress in a mouse model