代谢功能障碍相关脂肪肝诱发的抗氧化系统变化:综述。

IF 4.8 2区 医学 Q1 TOXICOLOGY Archives of Toxicology Pub Date : 2024-10-23 DOI:10.1007/s00204-024-03889-x
Gabriela Svobodová, Martin Horní, Eva Velecká, Iva Boušová
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引用次数: 0

摘要

代谢功能障碍相关性脂肪性肝病(MASLD)是一种以肝脏脂肪变性、炎症、随之而来的纤维化和肝硬化为特征的异质性疾病。脂质代谢的慢性损伤与氧化应激密切相关,导致细胞脂毒性、线粒体功能障碍和内质网应激。氧化应激的有害影响通常伴随着抗氧化防御机制的变化,许多临床和实验研究都报道了 MASLD 发生和发展过程中抗氧化酶表达/活性的改变。本综述将全面概述目前有关 MASLD 引起的主要抗氧化酶(超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶、谷胱甘肽 S-转移酶、谷胱甘肽还原酶、NAD(P)H:醌氧化还原酶)催化活性和表达变化以及非酶性抗氧化剂谷胱甘肽水平变化的研究。此外,还将概述维生素 E 在 MASLD 进展过程中对抗氧化酶的治疗作用。一般来说,在MASLD发展初期,抗氧化酶的表达/活性通常会增加,以保护生物体免受活性氧生成增加的影响。然而,在 MASLD 晚期,由于肝细胞和肝外细胞受损,几种抗氧化剂的表达/活性通常会下降,从而进一步加剧损伤。虽然在患者、各种实验动物或细胞模型中获得的结果并不一致,但综合来看,抗氧化酶在 MASLD 的发生和发展过程中的重要性已得到清楚的证明。
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Metabolic dysfunction-associated steatotic liver disease-induced changes in the antioxidant system: a review.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a heterogeneous condition characterized by liver steatosis, inflammation, consequent fibrosis, and cirrhosis. Chronic impairment of lipid metabolism is closely related to oxidative stress, leading to cellular lipotoxicity, mitochondrial dysfunction, and endoplasmic reticulum stress. The detrimental effect of oxidative stress is usually accompanied by changes in antioxidant defense mechanisms, with the alterations in antioxidant enzymes expression/activities during MASLD development and progression reported in many clinical and experimental studies. This review will provide a comprehensive overview of the present research on MASLD-induced changes in the catalytic activity and expression of the main antioxidant enzymes (superoxide dismutases, catalase, glutathione peroxidases, glutathione S-transferases, glutathione reductase, NAD(P)H:quinone oxidoreductase) and in the level of non-enzymatic antioxidant glutathione. Furthermore, an overview of the therapeutic effects of vitamin E on antioxidant enzymes during the progression of MASLD will be presented. Generally, at the beginning of MASLD development, the expression/activity of antioxidant enzymes usually increases to protect organisms against the increased production of reactive oxygen species. However, in advanced stage of MASLD, the expression/activity of several antioxidants generally decreases due to damage to hepatic and extrahepatic cells, which further exacerbates the damage. Although the results obtained in patients, in various experimental animal or cell models have been inconsistent, taken together the importance of antioxidant enzymes in MASLD development and progression has been clearly shown.

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来源期刊
Archives of Toxicology
Archives of Toxicology 医学-毒理学
CiteScore
11.60
自引率
4.90%
发文量
218
审稿时长
1.5 months
期刊介绍: Archives of Toxicology provides up-to-date information on the latest advances in toxicology. The journal places particular emphasis on studies relating to defined effects of chemicals and mechanisms of toxicity, including toxic activities at the molecular level, in humans and experimental animals. Coverage includes new insights into analysis and toxicokinetics and into forensic toxicology. Review articles of general interest to toxicologists are an additional important feature of the journal.
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