Fig. 9. Relationship between circadian rhythm and chemotherapy. The rhythm of the GSH content of mouse liver (black, based on data from ref. 225) is compared to the schedule of administration of oxaliplatin (Pt3) in a typical chronomodulated chemotherapy. Patients show best tolerance at 16:00 (red). Oxaliplatin is detoxified by conjugation to glutathione, hence, tolerance is linked directly to GSH levels (note the 12 h phase-shift between the highest GSH levels in mice and best tolerance in humans due to nocturnality of mice).