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Tenora et al., 2019

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On the other hand, AGAT and GAMT deficient patients who have reduced ability for de novo synthesis of creatine, can be successfully treated with oral creatine supplementation, although very high doses of creatine are used, and the replenishment of cerebral creatine takes months (Ganesan et al., 1997)

Nevertheless, longer-term exposures are frequently studied, often in combination with multiple time points, to examine the time-course variation of the metabolome, to understand the sequence of molecular initiating events leading to an adverse outcome pathway, and chronic toxicity upon repeated exposure to a given compound ( 2.3 Importance of including control and negative reference compounds A key aspect in drug-toxicity evaluation by in vitro metabolomics is the importance of including data from both non-hepatotoxic compounds as well as non-treated cells ( in vitro metabolomics studies, for instance, are often overlooked but can be a significant source of bias in the data, sometimes even more intense than the effects of the drug being tested