benzofurans and Arthritis--Gouty

Lithospermic acid (LSA) was originally isolated from the roots of Salvia mitiorrhiza, a common herb of oriental medicine. Previous studies demonstrated that LSA has antioxidant effects. In this study, we investigated the in vitro xanthine oxidase (XO) inhibitory activity, and in vivo hypouricemic and anti-inflammatory effects of rats. XO activity was detected by measuring the formation of uric acid or superoxide radicals in the xanthine/xanthine oxidase system. The results showed that LSA inhibited the formation of uric acid and superoxide radicals significantly with an IC50 5.2 and 1.08 microg/ml, respectively, and exhibited competitive inhibition. It was also found that LSA scavenged superoxide radicals directly in the system beta-NADH/PMS and inhibited the production of superoxide in human neutrophils stimulated by PMA and fMLP. LSA was also found to have hypouricemic activity on oxonate-pretreated rats in vivo and have anti-inflammatory effects in a model of gouty arthritis. These results suggested that LSA is a competitive inhibitor of XO, able to directly scavenge superoxide and inhibit superoxide production in vitro, and presents hypouricemic and anti-inflammatory actions in vivo.

Topics: Allopurinol; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Gouty; Benzofurans; Depsides; Disease Models, Animal; Dose-Response Relationship, Drug; Enzyme Inhibitors; Humans; Hyperuricemia; Inflammation; Male; Molecular Conformation; N-Formylmethionine Leucyl-Phenylalanine; Neutrophils; Oxonic Acid; Rats; Rats, Wistar; Reactive Oxygen Species; Tetradecanoylphorbol Acetate; Uric Acid; Xanthine Oxidase

The authors pay attention to benziodarone, a representative of the category of benzofurans. They test its effect on the uric acid serum level in normouraemic subjects as well as in hyperuricaemic syndrome and gouty arthritis. The hypouricaemic action of benziodarone (Amplivex-Labaz) is prompt. The maximum drop of uricaemia after Amplivex administration (2 tablets/day) occurs during the first three days. The uric acid level declines by as much as 80% of the baseline value. For long-term treatment 1 tablet per day is sufficient, in some instances even 1 tablet twice a week. The tolerance of the preparation is satisfactory. The authors deal also with the mechanism of action of benziodarone. Amplivex is not only a uricostatic but also a uricosuric agent.

Topics: Arthritis, Gouty; Benzofurans; Female; Humans; Male; Uric Acid; Uricosuric Agents