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对乙酰氨基酚在亚慢性暴露后会导致雄性奎氏溪蟾鱼出现内分泌紊乱和肝毒性。

Paracetamol causes endocrine disruption and hepatotoxicity in male fish Rhamdia quelen after subchronic exposure.

作者信息

Guiloski Izonete Cristina, Ribas João Luiz Coelho, Piancini Laercio Dante Stein, Dagostim Ana Carolina, Cirio Silvana Maris, Fávaro Luis Fernando, Boschen Suelen Lúcio, Cestari Marta Margarete, da Cunha Cláudio, Silva de Assis Helena Cristina

机构信息

Department of Pharmacology, Federal University of Paraná, Box 19031, 81530-990, Curitiba, PR, Brazil.

Department of Genetics, Federal University of Paraná, Box 19031, 81530-990, Curitiba, PR, Brazil.

出版信息

Environ Toxicol Pharmacol. 2017 Jul;53:111-120. doi: 10.1016/j.etap.2017.05.005. Epub 2017 May 8.

Abstract

Paracetamol is one of the most widely sold non-prescription drugs. This study aimed to evaluate the effects of the paracetamol on reproductive, biochemical, genetic, histopathological and hematogical biomarkers by waterborne exposure. Male fish of Rhamdia quelen were exposed to environmental concentrations of paracetamol (0, 0.25, 2.5μg/L) in a semi-static bioassay for 21days. Hemoglobin and hematocrit were reduced upon exposure to 0.25μg/L of paracetamol. Leukocytes and thrombocytes increased after paracetamol exposure. Paracetamol reduced testosterone levels in all exposed groups and increased estradiol levels at higher concentration. Serotonin and dopamine levels increased at exposure to 0.25μg/L. Paracetamol also caused protein carbonyls and increased SOD activity in fish exposed to 2.5μg/L and in addition led to an inhibition of EROD and GST activities in both concentrations. Hepatic genotoxicity occurred at the 0.25μg/L concentration. Hepatic tissues of exposed fish showed mild blood congestion and leucocytes infiltration. The results showed that paracetamol disrupted the hypothalamic-pituitary-gonadal axis, changed hematological parameters and caused hepatotoxicity in Rhamdia quelen. The findings suggest that this drug merits attention relative to its potential endocrine disrupter effect and hepatotoxicity, even at concentrations found in the aquatic environment.

摘要

对乙酰氨基酚是销售最为广泛的非处方药之一。本研究旨在通过水体暴露评估对乙酰氨基酚对生殖、生化、遗传、组织病理学和血液学生物标志物的影响。在半静态生物测定中,将奎氏溪蟾鱼雄鱼暴露于环境浓度的对乙酰氨基酚(0、0.25、2.5μg/L)中21天。暴露于0.25μg/L对乙酰氨基酚后,血红蛋白和血细胞比容降低。对乙酰氨基酚暴露后白细胞和血小板增加。对乙酰氨基酚降低了所有暴露组的睾酮水平,并在较高浓度下增加了雌二醇水平。暴露于0.25μg/L时血清素和多巴胺水平增加。对乙酰氨基酚还导致暴露于2.5μg/L的鱼体内蛋白质羰基增加和超氧化物歧化酶(SOD)活性增强,并且在两种浓度下均导致乙氧基异吩恶唑酮脱乙基酶(EROD)和谷胱甘肽S-转移酶(GST)活性受到抑制。在0.25μg/L浓度下出现肝脏遗传毒性。暴露鱼的肝脏组织显示轻度充血和白细胞浸润。结果表明,对乙酰氨基酚扰乱了奎氏溪蟾鱼的下丘脑-垂体-性腺轴,改变了血液学参数并导致肝脏毒性。研究结果表明,即使在水环境中发现的浓度下,这种药物因其潜在的内分泌干扰作用和肝脏毒性也值得关注。

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