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吡咯喹啉醌可改善环磷酰胺诱导的小鼠肝损伤。

Pyrroloquinoline quinone ameliorates liver injury in mice induced by cyclophosphamide.

机构信息

Zhejiang Provincial Engineering Technology Research Center of Marine Biomedical Products, School of Food and Pharmacy, Zhejiang Ocean University, Zhoushan, 316022, People's Republic of China.

Hangzhou Women's Hospital (Hangzhou Maternity and Child Health Care Hospital), Neonatal Intensive Care Unit, Hangzhou, 310008, People's Republic of China.

出版信息

Environ Sci Pollut Res Int. 2022 Apr;29(20):30383-30393. doi: 10.1007/s11356-021-17990-6. Epub 2022 Jan 8.

Abstract

The current study aimed to investigate the potential ameliorative effects of pyrroloquinoline quinone (PQQ) on cyclophosphamide (CTX)-induced liver injury in mice. The liver injury model was established by injecting mice with CTX (80 mg/kg/day). Liver function indices, antioxidant enzyme activities, and inflammatory cytokines were evaluated. In addition, protein expression levels of the nuclear factor E2-related factor 2 (Nrf2) and nuclear factor kappa-B (NF-κB) pathways in the liver tissues were determined using western blot. The results indicated that PQQ decreased the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and the malondialdehyde (MDA), interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α) levels in the liver tissues. Moreover, PQQ enhanced the activities of oxidative stress markers to alleviate CTX induced oxidative stress. Furthermore, the expression levels of heme oxygenase-1 (HO-1), glutamate-cysteine ligase modifier subunit (GCLM), and NAD(P)H quinone oxidoreductase 1 (NQO1) were significantly increased, and the expression levels of NF-κB p50, NF-κB p65, and inhibitor of NF-κB kinase alpha (IKKα) were significantly decreased after PQQ administration, suggesting that PQQ alleviated CTX-induced liver injury via activating the Nrf2-mediated antioxidant response pathway, and inhibiting the NF-κB-mediated inflammation pathway. Therefore, PQQ can be potentially used as a dietary supplement or functional foods for alleviating the CTX-induced liver injury.

摘要

本研究旨在探讨吡咯喹啉醌(PQQ)对环磷酰胺(CTX)诱导的小鼠肝损伤的潜在改善作用。通过给小鼠注射 CTX(80mg/kg/天)建立肝损伤模型。评估肝功能指标、抗氧化酶活性和炎症细胞因子。此外,还通过 Western blot 测定肝组织中核因子 E2 相关因子 2(Nrf2)和核因子 kappa-B(NF-κB)通路的蛋白表达水平。结果表明,PQQ 降低了血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)和肝组织中的丙二醛(MDA)、白细胞介素(IL)-1β、IL-6、肿瘤坏死因子-α(TNF-α)水平。此外,PQQ 增强了氧化应激标志物的活性,以减轻 CTX 诱导的氧化应激。此外,血红素加氧酶-1(HO-1)、谷氨酸半胱氨酸连接酶修饰亚基(GCLM)和 NAD(P)H 醌氧化还原酶 1(NQO1)的表达水平显著增加,而 NF-κB p50、NF-κB p65 和 NF-κB 激酶α抑制剂(IKKα)的表达水平在 PQQ 给药后显著降低,表明 PQQ 通过激活 Nrf2 介导的抗氧化反应途径和抑制 NF-κB 介导的炎症途径缓解 CTX 诱导的肝损伤。因此,PQQ 可作为膳食补充剂或功能性食品,用于缓解 CTX 诱导的肝损伤。

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