The ex vivo measurement of malondialdehyde and chemiluminescence as possible indices for anti-inflammatory drug evaluation.
A well-established model of foot-pad oedema in the rat, an example of a cell-mediated hypersensitivity reaction, was used in this study. Male rats were immunized on day 0 with Freund's complete adjuvant (FCA) and then challenged 6 days later with FCA in one hind paw. Within 4 h of the initiation of this acute inflammatory reaction, the presence of free radicals was detected as luminol-amplified chemiluminescence (LAC) directly from the inflamed paws. In addition, an increase in malondialdehyde (MDA), an end product of lipid peroxidation, was measured in both inflamed tissue and plasma. Groups of animals were treated with either diclofenac sodium, indomethacin, piroxicam or prednisolone either 1 h before or 6 h after challenge, oedema, LAC and MDA being measured at various times after challenge. The three non-steroidal anti-inflammatory drugs (NSAIDs) and prednisolone, given 1 h before challenge, significantly inhibited LAC and plasma MDA levels at 4 h post challenge. When given 6 h after challenge all drugs significantly inhibited oedema at 24 h. Furthermore, all the drugs inhibited tissue MDA and LAC but only indomethacin and piroxicam reached significance. The data suggest a role for lipid peroxidation and free-radical generation in inflammation and provide possible indices for in vivo drug activity and evaluation.
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D004487:Edema / Q000276:immunology / Q000378:metabolism; D005609:Free Radicals; D008054:Lipid Peroxides / Q000096:biosynthesis; D008163:Luminescent Measurements; D008165:Luminol; D008297:Male; D008314:Malonates / Q000378:metabolism*; D008315:Malondialdehyde / Q000378:metabolism*; D009169:Mycobacterium tuberculosis / Q000276:immunology; D051381:Rats; D011919:Rats, Inbred Strains
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005609:Free Radicals; D008054:Lipid Peroxides; D008314:Malonates; D008315:Malondialdehyde; D008165:Luminol