Acetaminophen, molecular model synthesis

Recently, we established a GSH-knockdown rat model for the prediction of human hepatotoxicity (Akai et al. 2007). An adenovirus vector with short hairpin RNA against rat y-glutamylcysteine synthetase (GCS) heavy chain subunit was constructed and used to knockdown GSH synthesis. This rat model, with an 80% decreased hepatic GSH level, demonstrated a high sensitivity for acetaminophen-induced hepatotoxicity. With the advance of molecular biology, novel animal models will be established and applied to drug development in the near future. 

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