The roles of active oxygen, lipid peroxidation, and the antioxidative defence mechanism in gastric mucosal injury induced by treatment with indomethacin in rats were investigated. The The present study was undertaken in rats to measure changes in lipid peroxides and antioxidants in serum samples and gastric mucosa after administration of indomethacin. Also, we investigated the effects of a superoxide radical scavenger (superoxide dismutase (SOD)), a hydrogen peroxide scavenger (catalase), and a hydroxyl radical scavenger (dimethylsulphoxide (DMSO)) on gastric mucosal injury and lipid peroxide formation induced by giving indomethacin to rats, and the effects ofa combination of SOD and catalase on indomethacin induced changes in antioxidants.

ABSTRACT. Lactoferrin (LF) is a ubiquitous protein which exists in milk, plasma, synovial fluids, cerebrospinal fluid and other biological fluids. LF is also well known as a natural immunomodulator. Recently, we found that bovine milk-derived LF (BLF) produced µ-opioid receptor-mediated analgesia. In this study, we examined whether oral administration of BLF causes anti-nociceptive and anti-inf lammatory effects, and also whether it modulates LPS-induced TNF-α and IL-10 production in rat model of rheumatoid arthritis (RA), rat adjuvant arthritis. BLF was administrated once daily, starting 3 hr before (preventive experiment) or 19 days after (therapeutic experiment) adjuvant injection. In both experiments, BLF suppressed the development of arthritis and the hyperalgesia in the adjuvant-injec ted paw. The single-administered BLF produced a dose-dependent analgesia, which was reversed by naloxone, in the adjuvant arthritis rats. Both repeated and single administration of BLF suppressed TNF-α production and increased IL-10 production in the LPS-stimulated adjuvant arthritis rats. These results suggest that orally administered BLF has both preventive and therapeutic effects on the developme nt of adjuvant-induced inflammation and pain. Moreover, the immunomodulatory properties of BLF, such as down-regulation of TNF-α and upregulation of IL-10, could be beneficial in the treatment of RA. Thus, we concluded that LF can be safely used as a natural drug for RA patients suffering from joint pain.

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