Oxidative state and oxidative metabolism of the heart from rats with adjuvant-induced arthritis.

The aim of the present work was to investigate, in a more extensive way, the oxidative state and parameters related to energy metabolism of the heart tissue of rats using the model of adjuvant-induced arthritis. The latter is a model for the human arthritic disease. Measurements were done in the total tissue homogenate, isolated mitochondria and cytosolic fraction. The adjuvant-induced arthritis caused several modifications in the oxidative state of the heart which, in general, indicate an increased oxidative stress (+80% reactive oxygen species), protein damage (+53% protein carbonyls) and lipid damage (+63% peroxidation) in the whole tissue. The distribution of these changes over the various cell compartments was frequently unequal. For example, protein carbonyls were increased in the whole tissue and in the cytosol, but not in the mitochondria. No changes in GSH content of the whole tissue were found, but it was increased in the mitochondria (+33%) and decreased in the cytosol (-19%). The activity of succinate dehydrogenase was 77% stimulated by arthritis; the activities of glutamate dehydrogenase, isocitrate dehydrogenase and cytochrome c oxidase were diminished by 31, 25 and 35.3%, respectively. In spite of these alterations, no changes in the mitochondrial respiratory activity and in the efficiency of energy transduction were found. It can be concluded that the adjuvant-induced arthritis in rats causes oxidative damage to the heart with an unequal intracellular distribution. Compared to the liver and brain the modifications caused by arthritis in the heart are less pronounced on variables such as GSH levels and protein integrity. Possibly this occurs because the antioxidant system of the heart is less impaired by arthritis than that reported for the former tissues. Even so, the modifications caused by arthritis represent an imbalanced situation that probably contributes to the cardiac symptoms of the arthritis disease.

Green tea extract improves the oxidative state of the liver and brain in rats with adjuvant-induced arthritis.

The purpose of the study was to evaluate the possible effects of the administration of a green tea extract on the oxidative state of the liver and brain of adjuvant-induced arthritic rats, a model for human rheumatoid arthritis. Daily doses of 250 mg kg(-1) (59.8 mg catechins per kg) for 23 days were administered. This treatment produced significant diminutions in protein and lipid damage in liver, brain and plasma. It also diminished the tissue ROS contents and increased the antioxidant capacity of the plasma. The antioxidant defenses, which are diminished by arthritis, were improved by the green tea treatment, as revealed by the restoration of the GSH and protein thiol levels and by the strong tendency for normalizing the activities of the antioxidant enzymes. The activity of glucose 6-phosphate dehydrogenase, which is increased by arthritis in the liver, was also almost normalized by the treatment. In conclusion, it can be said that green tea consumption is possibly beneficial for the liver and brain of patients suffering from rheumatoid arthritis because it attenuates the pronounced oxidative stress that accompanies the disease and, thus, diminishes the injury to lipids and proteins in both liver and brain. There are also indications that, in the liver, the green tea can contribute to normalize the metabolic functions that are substantially modified by arthritis. For example, the green tea normalized the activity of glucose 6-phosphate dehydrogenase, a key enzyme of an important metabolic route (pentose monophosphate pathway). It is expected that the green tea treatment is equally able to normalize the activity of other enzymes (e.g., glucokinase and glucose 6-phosphatase), a hypothesis to be tested by future work.

Oxidative state and oxidative metabolism in the brain of rats with adjuvant-induced arthritis.

The purpose of the present study was to evaluate the oxidative status of the brain of arthritic rats, based mainly on the observation that arthritis induces a pronounced oxidative stress in the liver of arthritis rats and that morphological alterations have been reported to occur in patients with rheumatoid arthritis. Rats with adjuvant-induced arthritis were used. These animals presented higher levels of reactive oxygen species (ROS) in the total brain homogenate (25% higher) and in the mitochondria (+55%) when compared to healthy rats. The nitrite plus nitrate contents, nitric oxide (NO) markers, were also increased in both mitochondria (+27%) and cytosol (+14%). Arthritic rats also presented higher levels of protein carbonyl groups in the total homogenate (+43%), mitochondria (+69%) and cytosol (+145%). Arthritis caused a diminution of oxygen consumption in isolated brain mitochondria only when ascorbate was the electron donor. The disease diminished the mitochondrial cytochrome c oxidase activity by 55%, but increased the transmembrane potential by 16%. The pro-oxidant enzyme xanthine oxidase was 150%, 110% and 283% higher, respectively, in the brain homogenate, mitochondria and cytosol of arthritic animals. The same occurred with the calcium-independent NO-synthase activity that was higher in the brain homogenate (90%) and cytosol (122%) of arthritic rats. The catalase activity, on the other hand, was diminished by arthritis in all cellular fractions (between 30 and 40%). It is apparent that the brain of rats with adjuvant-induced arthritis presents a pronounced oxidative stress and a significant injury to lipids and proteins, a situation that possibly contributes to the brain symptoms of the arthritis disease.