Actions of multiple doses of resveratrol on oxidative and inflammatory markers in plasma and brain of healthy and arthritic rats.

The actions of resveratrol in brain and plasma of rats with adjuvant-induced arthritis were investigated. Resveratrol was administered orally during a period of 23 days. A major concern of the present work was to explore an ample range of daily doses (10-200 mg/kg). Several oxidative and inflammatory markers were measured. Important effects of resveratrol treatment were the normalization of the plasma myeloperoxidase activity (inflammatory marker), the normalization of the brain xanthine oxidase activity (reactive oxygen species source) and the near-normalization of the catalase activity in the brain (antioxidant defence). These effects presented obvious dose dependencies in the range up to 200 mg/kg. Resveratrol also reduced protein and lipid damage within the lowest dose ranges investigated, and its action as a free radical scavenger activity was enhanced in brain mitochondria of arthritic rats. Resveratrol failed in restoring the diminished albumin levels and plasma protein thiols in arthritic rats. The latter, however, were substantially increased in healthy rats at low doses (up to 50 mg/kg), a sign of antioxidant action. This increase was reversed at higher doses, a sign of pro-oxidant action. The observations agree with the notion that low doses of resveratrol might be useful as an adjuvant to the conventional antirheumatic drugs.

A reappraisal of the proposed metabolic and antioxidant actions of butylated hydroxytoluene (BHT) in the liver.

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, 10-9 to 10-6  M, could not be confirmed. BHT, however, increased reactive oxygen species (ROS) production in isolated mitochondria, starting at the concentration of 10-8  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.