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半胱天冬酶在展青霉素诱导的体外和体内肝毒性中的作用。

Involvement of caspase in patulin-induced hepatotoxicity in vitro and in vivo.

机构信息

College of Life Science and Engineering, Lanzhou University of Technology, Lanzhou, Gansu, 730050, China.

College of Life Science and Engineering, Lanzhou University of Technology, Lanzhou, Gansu, 730050, China.

出版信息

Toxicon. 2022 Jan 30;206:64-73. doi: 10.1016/j.toxicon.2021.12.017. Epub 2021 Dec 28.

Abstract

Patulin (PAT) a kind of mycotoxin, is a widely disseminated mycotoxin found in agricultural products and could cause liver damage. However, evidence on the underlying mechanisms of patulin is still lacking. In the present study, Human liver cancer cells (HepG2) together with a mouse model were used to explore the possible effect and mechanism. The results demonstrated that PAT treatment inhibited cell proliferation and caused liver toxicity in mice. In vitro, PAT inhibited the growth of HepG2 cells in a dose-dependent manner and a time-dependent manner; lipid peroxidation, malondialdehyde (MDA) production increased and the level of SOD and GSH in cells changed significantly. In vivo, Kunming mice were treated with PAT(2.5-15 μM), We indicated that liver damage are observed. The activity of serum alanine transaminase (ALT) and aspartate transaminase (AST) were increased significantly, the hepatocyte nucleus stained with Hematoxylin and Eosin (HE) was blurred and deformed. we also explored the lipid peroxidation and enzymes related to redox and found that the activities of SOD in animals do not change significantly, not like that in cells, while GSHpx played a major role. In addition, we measured the caspase activity of cells and the expression of caspase in mice. PAT-induced the caspase cascade was confirmed with the elevation of the activity and expression of caspase. These data suggest that PAT treatment altered both the redox systems in cells and animals. involvement of caspase in patulin-induced hepatotoxicity.

摘要

棒曲霉素(PAT)是一种广泛存在于农产品中的真菌毒素,可导致肝损伤。然而,关于棒曲霉素的潜在作用机制的证据仍然缺乏。在本研究中,使用人肝癌细胞(HepG2)和小鼠模型来探讨可能的作用和机制。结果表明,PAT 处理抑制了细胞增殖并导致了小鼠的肝毒性。在体外,PAT 以剂量和时间依赖的方式抑制 HepG2 细胞的生长;脂质过氧化,丙二醛(MDA)产生增加,细胞内 SOD 和 GSH 水平明显变化。在体内,昆明小鼠用 PAT(2.5-15μM)处理,我们观察到肝损伤。血清丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST)的活性显著增加,苏木精和伊红(HE)染色的肝细胞核模糊变形。我们还研究了脂质过氧化和与氧化还原相关的酶,发现动物体内 SOD 的活性没有明显变化,不像细胞内那样,而 GSHpx 则起主要作用。此外,我们测量了细胞和小鼠中 caspase 的活性和表达。PAT 诱导的胱天蛋白酶级联反应通过胱天蛋白酶活性和表达的升高得到证实。这些数据表明,PAT 处理改变了细胞和动物的氧化还原系统。胱天蛋白酶参与棒曲霉素诱导的肝毒性。

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