PPIG and lactic acidosis: However, it is clear from recent in vitro studies, in eg, HepG2 cells which are deficient in CYP450 activity, that APAP can also act as CYP metabolism-independent cytotoxin (Behrends et al., 2019).This type of toxicity was linked to “a decoupling of glycolysis from the TCA cycle, lactic acidosis, reduced NADPH production and subsequent suppression of the anabolic pathways required for rapid growth” (Behrends et al., 2019), providing a mechanism for cell death that is independent of oxidative stress.