A metabolomics cell-based approach for anticipating and investigating drug-induced liver injury

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)

The fungal colonisation of rock-art caves: experimental evidence

The conservation of rock-art paintings in European caves is a matter of increasing interest. This derives from the bacterial colonisation of Altamira Cave, Spain and the recent fungal outbreak of Lascaux Cave, France—both included in the UNESCO World Heritage List. Here, we show direct evidence of a fungal colonisation of rock tablets in a testing system exposed in Altamira Cave. After 2 months, the tablets, previously sterilised, were heavily colonised by fungi and bacteria. Most fungi isolated were labelled as entomopathogens, while the bacteria were those regularly identified in the cave. Rock colonisation was probably promoted by the dissolved organic carbon supplied with the dripping and condensation waters and favoured by the displacement of aerosols towards the interior of the cave, which contributed to the dissemination of microorganisms. The role of arthropods in the dispersal of spores may also help in understanding fungal colonisation. This study evidences the fragility of rock-art caves and demonstrates that microorganisms can easily colonise bare rocks and materials introduced into the cavity