FOLFOX Toxicity and Antioxidant Therapy

To determine the direct toxicity of FOLFOX, 10-week old C57Bl/6 mice were treated with intraperitoneal (i.p.) oxaliplatin 6 mkg/kg followed 2 h later by 5-FU 50 mg/kg and folinic acid 90 mg/kg (all obtained from Sigma-Aldrich, Dorset, UK), on a weekly basis for 5 weeks. The drug dosing schedule was based upon that used in previously published studies and our own preliminary dose finding experiments [12] (link), [13] (link), [14] (link). Control animals received vehicle alone. There were 10 animals per treatment group, although one animal in each group died during the course of the experiment. Mice were culled one week after the final dose of chemotherapy under isoflurane anaesthesia by cardiac puncture. All animals received standard animal house care, including ad libitum access to water and a standard purified diet (D01060501, Research Diets Inc, New Brunswick, USA).
To determine the effect of antioxidant therapy on the development of FOLFOX induced SOS, the above experiments were repeated (n = 5 per group) with custom diets supplemented with either 3% N-acetylcysteine or 0.7% butylated hydroxyanisole (Research Diets Inc, New Brunswick, USA). Based upon a typical dietary intake of 150 g food per kg body weight, this equated to a daily dose of 4.5 g/kg NAC and 1 g/kg BHA per day. The diets were otherwise identical to the standard purified diet used above. There was one death in the FOLFOX treated group receiving a BHA supplemented diet.