Abstract：
:In preclinical stages of drug development, anticipating potential adverse drug effects such as toxicity is an important issue for both saving resources and preventing public health risks. Current in vitro cytotoxicity tests are restricted by their predictive potential and their ability to provide mechanistic information. This study aimed to develop a metabolomic mass spectrometry-based approach for the detection and classification of drug-induced hepatotoxicity. To this end, the metabolite profiles of human derived hepatic cells (i.e., HepG2) exposed to different well-known hepatotoxic compounds acting through different mechanisms (i.e., oxidative stress, steatosis, phospholipidosis, and controls) were compared by multivariate data analysis, thus allowing us to decipher both common and mechanism-specific altered biochemical pathways. Briefly, oxidative stress damage markers were found in the three mechanisms, mainly showing altered levels of metabolites associated with glutathione and γ-glutamyl cycle. Phospholipidosis was characterized by a decreased lysophospholipids to phospholipids ratio, suggestive of phospholipid degradation inhibition. Whereas, steatosis led to impaired fatty acids β-oxidation and a subsequent increase in triacylglycerides synthesis. The characteristic metabolomic profiles were used to develop a predictive model aimed not only to discriminate between non-toxic and hepatotoxic drugs, but also to propose potential drug toxicity mechanism(s).
journal_name
Sci Repjournal_title
Scientific reportsauthors
García-Cañaveras JC,Castell JV,Donato MT,Lahoz Adoi
10.1038/srep27239subject
Has Abstractpub_date
2016-06-06 00:00:00pages
27239issn
2045-2322pii
srep27239journal_volume
6pub_type
杂志文章abstract：:Weight regain is one of the most common problems in the long-term after bariatric surgery. It is unknown if high-intensity exercise programs applied in late phases of post-surgical follow-up could counteract this trend. After a 3-year follow-up, 21 patients underwent sleeve gastrectomy were randomized into an exercise...
journal_title：Scientific reports
pub_type： 杂志文章,随机对照试验
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pub_type： 杂志文章
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更新日期：2016-05-24 00:00:00
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pub_type： 杂志文章
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pub_type： 杂志文章
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pub_type： 临床试验,杂志文章
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pub_type： 杂志文章
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