Antiinflammatory drugs: protection of a bacterial virus as an in vitro biological measure of free radical activity.
The effects of the hydroxyl free radical (OH), the superoxide free radical (O2-) and the trichloromethyl peroxy free radical (CC13O2) on the survival of bacteriophage T2 have been studied in the absence and presence of several non-steroidal anti-inflammatory drugs (NSAID). The trichloromethylperoxy radical derived from carbon tetrachloride is considerably more effective than the hydroxyl radical in inactivating the virus: the superoxide radical has only a minor inactivating effect. All the NSAID investigated (flurbiprofen, ibuprofen, sulindac, piroxicam, benoxaprofen, mefenamic acid, diflunisal, aspirin, D-penicillamine, indomethacin and metiazinic acid) inhibit inactivation by OH. This is in agreement with the high rate constants of reaction with this radical determined using the fast reaction technique of pulse radiolysis, i.e. (k greater than 10(9) M-1 S-1). The sulphur-containing drugs, metiazinic acid, piroxicam, penicillamine and sulindac as well as the indole derivative indomethacin, protect the virus from inactivation by the model peroxy radical CC13O2 (the dose modifying factor, DMF greater than 20). In contrast, acetylsalicylic acid related drugs, such as diflunisal, the anthranilic acid derivative, mefenamic acid, and some phenylpropionic acid derivatives, such as flurbiprofen, exhibit only a very small or no protective effect (DMF less than 2). As with OH, the ability of the drugs to protect the virus from inactivation by the peroxy radical is in agreement with their corresponding rate constants of reaction determined by pulse radiolysis.
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D005609:Free Radicals; D006878:Hydroxides / Q000378:metabolism / Q000494:pharmacology; D017665:Hydroxyl Radical; D007700:Kinetics; D010545:Peroxides / Q000378:metabolism / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism / Q000494:pharmacology; D013604:T-Phages / Q000187:drug effects*
D000893:Anti-Inflammatory Agents; D005609:Free Radicals; D006878:Hydroxides; D010545:Peroxides; D013481:Superoxides; D017665:Hydroxyl Radical; C029952:trichloromethylperoxy radical