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Butylated hydroxytoluene (BHT) was investigated for its metabolic actions in the perfused rat liver. Contrary to what is expected from an uncoupler, BHT up to 500 μM did not stimulate oxygen uptake nor did it inhibit gluconeogenesis from lactate. Transformation of fructose into glucose was also not affected by BHT; only lactate production was slightly increased at the concentration of 100 μM. The uncoupling effect of BHT in isolated mitochondria was confirmed, but only at concentrations above 10 μM; uncoupling at lower concentrations, 10 to 10 M, could not be confirmed. BHT, however, increased reactive oxygen species (ROS) production in isolated mitochondria, starting at the concentration of 10 M. This is the opposite of what can be expected from a compound with proven ex vivo antioxidant action. One cannot exclude the possibility that, in mitochondria, stimulation of ROS production rather than uncoupling could be the most significant effect of BHT.

Chronic and systemic inflammation affecting the synovial membranes, articular cartilages and bones is the most evident symptom of rheumatoid arthritis. 1 The intense hyperplasia of the articular cartilage takes place with participation of T cells, B cells, macrophages, fibroblasts and pro-inflammatory cytokines, particularly interleukin-1 beta (IL-1β), interleukin-6 (IL-6) and tumour necrosis factor alpha (TNFα). 2 Reactive oxygen species, however, also play an important role because the overproduction of pro-inflammatory cytokines stimulates neutrophils and activated macrophages to secrete various kinds of reactive substances in the synovial fluid. 3,4 Furthermore, cytokines released into the synovium also reach the systemic circulation and act in other tissues. Consequently, oxidative stress biomarkers are increased in

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