Modulation of adipogenesis and lipogenesis by indomethacin and pantoprazole

IF 2.6 3区 医学 Q3 TOXICOLOGY
Bita Entezari , Hasan Akbaba , Hande Gurer-Orhan
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引用次数: 0

Abstract

Endocrine disruptors are suggested to act as potential “obesogens” by interacting with various metabolic processes in adipose tissue. Besides industrial chemicals that are blamed for acting as endocrine disruptors as well as obesogens, pharmaceuticals can also cause obesogenic effects as unintended adverse effects. However, limited studies evaluated the obesogenic adverse effects of pharmaceuticals. Based on this information, the present study aimed to investigate the possible in vitro adipogenic/lipogenic potential of indomethacin and pantoprazole that are prescribed during pregnancy. Their effects on lipid accumulation, adiponectin level, glycerol-3-phosphate dehydrogenase (G3PDH) activity, and expression of adipogenic genes and proteins were investigated in 3 T3-L1 cell line. The range of concentrations of the pharmaceuticals was selected according to their Cmax values. Lipid accumulation was increased dependently with indomethacin dose and with pantoprazole at its highest concentration. Both pharmaceuticals also increased adiponectin levels, which was thought to play a role in stimulating the adipogenesis pathway. Moreover, both pharmaceuticals altered the gene and/or protein expression of some adipogenic/lipogenic transcriptional factors, which may lead to disruption of metabolic pathways during the fetal period. In conclusion, indomethacin and pantoprazole may have obesogenic effects through different mechanisms and their potential to cause obesity should be investigated by further in vivo and epidemiological studies.

Abstract Image

吲哚美辛和泮托拉唑对脂肪生成和脂肪生成的调节作用
有人认为,内分泌干扰素会与脂肪组织的各种代谢过程发生作用,从而成为潜在的 "肥胖诱因"。除了工业化学品被指责为内分泌干扰物和肥胖诱发剂外,药物也可能作为意外的不良反应导致肥胖。然而,对药物致肥不良影响的评估研究有限。基于这些信息,本研究旨在调查孕期处方药吲哚美辛和泮托拉唑可能的体外致脂肪/致脂潜能。研究人员在 3 个 T3-L1 细胞系中调查了这两种药物对脂质积累、脂肪粘连素水平、甘油-3-磷酸脱氢酶(G3PDH)活性以及脂肪生成基因和蛋白质表达的影响。根据 Cmax 值选择了药物的浓度范围。吲哚美辛和泮托拉唑在最高浓度下都会增加脂质积累。这两种药物还能增加脂肪连蛋白的水平,这被认为在刺激脂肪生成途径中发挥作用。此外,这两种药物还改变了一些脂肪生成/脂肪生成转录因子的基因和/或蛋白质表达,这可能会导致胎儿期代谢途径的中断。总之,吲哚美辛和泮托拉唑可能通过不同的机制产生致肥胖作用,它们导致肥胖的可能性应通过进一步的体内研究和流行病学研究进行调查。
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来源期刊
Toxicology in Vitro
Toxicology in Vitro 医学-毒理学
CiteScore
6.50
自引率
3.10%
发文量
181
审稿时长
65 days
期刊介绍: Toxicology in Vitro publishes original research papers and reviews on the application and use of in vitro systems for assessing or predicting the toxic effects of chemicals and elucidating their mechanisms of action. These in vitro techniques include utilizing cell or tissue cultures, isolated cells, tissue slices, subcellular fractions, transgenic cell cultures, and cells from transgenic organisms, as well as in silico modelling. The Journal will focus on investigations that involve the development and validation of new in vitro methods, e.g. for prediction of toxic effects based on traditional and in silico modelling; on the use of methods in high-throughput toxicology and pharmacology; elucidation of mechanisms of toxic action; the application of genomics, transcriptomics and proteomics in toxicology, as well as on comparative studies that characterise the relationship between in vitro and in vivo findings. The Journal strongly encourages the submission of manuscripts that focus on the development of in vitro methods, their practical applications and regulatory use (e.g. in the areas of food components cosmetics, pharmaceuticals, pesticides, and industrial chemicals). Toxicology in Vitro discourages papers that record reporting on toxicological effects from materials, such as plant extracts or herbal medicines, that have not been chemically characterized.
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