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双酚A和壬基酚对大鼠肝肾功能损伤的拮抗作用。

The antagonistic effect of bisphenol A and nonylphenol on liver and kidney injury in rats.

作者信息

Shi Rui, Liu Zirong, Liu Tong

机构信息

Department of Hepatobiliary Surgery, Tianjin First Central Hospital, Tianjin, China.

Department of General surgery, General Hospital of Tianjin Medical University, Tianjin, China.

出版信息

Immunopharmacol Immunotoxicol. 2021 Oct;43(5):527-535. doi: 10.1080/08923973.2021.1950179. Epub 2021 Jul 20.

Abstract

OBJECTIVE

Bisphenol A (BPA) and nonylphenol (NP) are widely distributed endocrine-disrupting compounds. We aimed to estimate the combined toxicity of BPA and NP at a clinically safe dose (100 μg/kg) in rats.

MATERIALS AND METHODS

Liver and kidney functions were evaluated by detecting the relevant indicators. Hematoxylin and Eosin (HE) staining was performed to examine the injury in the tissue. TUNEL assay and Western blot were used to detect cell apoptosis and expressions of target factors, respectively.

RESULTS

The body weight of rats in the BPA + NP group was lighter than that in the BPA or NP group. BPA or NP weakened liver function through increasing levels of aspartate aminotransferase (AST), alkaline phosphatase (ALP), alanine aminotransferase (ALT), cholesterol (CHOL), triglyceride TG, globulin (GLOB), treponemiapallidum (TP), and total bilirubin (TBIL). BPA and NP could induce kidney damage by elevating the levels of serum creatinine (Scr) and blood urea nitrogen (BUN). Moreover, the malondialdehyde (MDA) content was increased, whereas the activities of superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GSH-PX), glutathione sulfotransferase (GSH-ST), catalase (CAT), and peroxidase (POD) were reduced in those groups exposed to BPA or NP. HE staining exhibited injuries of the liver and kidney. Furthermore, the apoptosis of liver and kidney cells was enhanced by exposure to BPA or NP. Additionally, the expressions of CYP2D6, CYP1A1, and CYP2E1 were triggered by the treatment of BPA or NP. The combined effect of BPA and NP seemed to be antagonistic at a low dose.

CONCLUSION

BPA and NP may have potential interactions.

摘要

目的

双酚A(BPA)和壬基酚(NP)是广泛分布的内分泌干扰化合物。我们旨在评估BPA和NP在大鼠临床安全剂量(100μg/kg)下的联合毒性。

材料与方法

通过检测相关指标评估肝肾功能。进行苏木精-伊红(HE)染色以检查组织损伤。分别采用TUNEL法和蛋白质免疫印迹法检测细胞凋亡及靶因子表达。

结果

BPA+NP组大鼠体重低于BPA组或NP组。BPA或NP通过升高天冬氨酸转氨酶(AST)、碱性磷酸酶(ALP)、丙氨酸转氨酶(ALT)、胆固醇(CHOL)、甘油三酯(TG)、球蛋白(GLOB)、梅毒螺旋体(TP)和总胆红素(TBIL)水平削弱肝功能。BPA和NP可通过升高血清肌酐(Scr)和血尿素氮(BUN)水平诱导肾损伤。此外,在暴露于BPA或NP的组中,丙二醛(MDA)含量增加,而超氧化物歧化酶(SOD)、谷胱甘肽(GSH)、谷胱甘肽过氧化物酶(GSH-PX)、谷胱甘肽硫转移酶(GSH-ST)、过氧化氢酶(CAT)和过氧化物酶(POD)活性降低。HE染色显示肝和肾有损伤。此外,暴露于BPA或NP可增强肝和肾细胞的凋亡。另外,BPA或NP处理可引发细胞色素P450 2D6(CYP2D6)、细胞色素P450 1A1(CYP1A1)和细胞色素P450 2E1(CYP2E1)的表达。BPA和NP在低剂量时的联合作用似乎具有拮抗作用。

结论

BPA和NP可能存在潜在相互作用。

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