使用硫化氢、维生素 E 和 Necrostatin-1 对抗乙酰氨基酚诱导的大鼠肝毒性的潜在益处。
Potential benefits of using hydrogen sulfide, vitamin E and necrostatin-1 to counteract acetaminophen‑induced hepatotoxicity in rats.
出版信息
Bratisl Lek Listy. 2021;122(10):732-738. doi: 10.4149/BLL_2021_117.
BACKGROUND
The use of acetaminophen (APAP) is increasing recently, especially with COVID-19 outbreaks. APAP is safe at therapeutic levels, however, an overdose can cause severe liver injury. This study aims to explore possible mechanisms involved in APAP‑induced hepatotoxicity and compare different hepatoprotective agents, namely vitamin E, hydrogen sulfide (H2S) and necrostatin-1 (NEC-1).
METHODS
Adult male albino rats were divided into groups: Control group, APAP‑induced hepatotoxicity group, Vitamin E‑treated group, H2S‑treated group and NEC-1‑treated group. Serum levels for aspartate aminotransferase (AST), alanine aminotransferase (ALT), interleukin-33 (IL-33), tumor necrosis factor alpha (TNF-α), reduced glutathione (GSH) and lipid profile were measured. Histopathological examinations of liver tissue with H(et)E stain and immunohistochemistry for activated caspase-3 were also done.
RESULTS
APAP‑treated group showed elevated liver transaminases, hyperlipidemia, and deficient liver anti-oxidative response together with disturbed hepatic architecture and increased immune-expression of activated caspase-3 in hepatic tissue. Pretreatment with vitamin E, H2S or NEC-1 reversed the affected parameters. Vitamin E and H2S showed greater improvement when compared to NEC-1.
CONCLUSION
Vitamin E, H2S and NEC-1 showed protective effects against APAP-induced hepatotoxicity, thus they may be used as an adjuvant therapy when APAP is indicated for long periods as is the case in COVID-19 patients (Tab. 2, Fig. 2, Ref. 45). Text in PDF www.elis.sk Keywords: acetaminophen, hepatotoxicity, apoptosis, necrostatin-1, vitamin E, H2S.
背景
最近，对乙酰氨基酚（APAP）的使用量不断增加，尤其是在 COVID-19 爆发期间。APAP 在治疗水平下是安全的，但是过量会导致严重的肝损伤。本研究旨在探讨 APAP 诱导的肝毒性的可能机制，并比较不同的肝保护剂，即维生素 E、硫化氢（H2S）和 Necrostatin-1（NEC-1）。
方法
将成年雄性白化大鼠分为对照组、APAP 诱导的肝毒性组、维生素 E 治疗组、H2S 治疗组和 NEC-1 治疗组。测定血清中天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）、白细胞介素-33（IL-33）、肿瘤坏死因子-α（TNF-α）、还原型谷胱甘肽（GSH）和血脂水平。还对肝组织进行 H（et）E 染色和活化的 caspase-3 免疫组化检查。
结果
APAP 处理组的肝转氨酶升高、血脂异常、肝抗氧化反应不足，肝组织结构紊乱，肝组织中活化的 caspase-3 的免疫表达增加。维生素 E、H2S 或 NEC-1 的预处理逆转了受影响的参数。与 NEC-1 相比，维生素 E 和 H2S 显示出更好的改善效果。
结论
维生素 E、H2S 和 NEC-1 对 APAP 诱导的肝毒性具有保护作用，因此，在 COVID-19 患者中需要长时间使用 APAP 的情况下（例如），它们可以用作辅助治疗（表 2，图 2，参考 45）。
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