Myocrisin-mediated oxidative stress.
This study reports on the ability of myocrisin to mediate in the production and detoxification of oxidants (principally hydrogen peroxide) in the monocyte in-vivo and in-vitro. The hydrogen peroxide produced by the monocyte derived from rheumatoid arthritis patients being treated with myocrisin was found to be 14.9 +/- 1.6 nmoles/10(6) cells and is elevated above levels found in monocytes obtained from patients either being treated with non-steroidal anti-inflammatory drugs (NSAIDs) (11.3 +/- 0.4 nmoles/10(6) cells; P < 0.01) or normal healthy volunteers (11.2 +/- 1.2 nmoles/10(6) cells; P < 0.01). A comparative study on glutathione (GSH) oxidation indicated that levels of monocyte GSH were elevated in myocrisin-treated patients (2.4 +/- 0.49 mmol/l) over normal healthy volunteers (0.83 +/- 0.18 mM; P < 0.01) and that levels of monocyte diglutathione (GSSG) were depressed (myocrisin, 0.97 +/- 0.41 micromol/l; normal, 5.71 +/- 0.73 micromol/l; P < 0.01). The non-inhibition of glutathione reductase and the inhibition of glutathione peroxidase by gold provides the link between these two observations. Thus, gold therapy would seem to elevate monocyte hydrogen peroxide, increase monocyte reduced glutathione and decrease plasma glutathione peroxidase activity. Subsequently, the data from this small group of patients (n = 10) provides an indication that, in-vivo, myocrisin contributes to an increase in oxidative stress.
Reglinski
J
J
Department of Pure and Applied Chemistry, Strathclyde University, Glasgow, UK. j.reglinski@strath.ac.uk
Paterson
D E
DE
Latimer
S
S
Campbell
J M
JM
Wilson
R
R
Porter
D
D
Sturrock
R D
RD
Smith
W E
WE
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000188:drug therapy; D005260:Female; D005978:Glutathione / Q000097:blood; D005979:Glutathione Peroxidase / Q000037:antagonists & inhibitors; D006052:Gold Sodium Thiomalate / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D018384:Oxidative Stress
D000894:Anti-Inflammatory Agents, Non-Steroidal; D018501:Antirheumatic Agents; D006052:Gold Sodium Thiomalate; D006861:Hydrogen Peroxide; D005979:Glutathione Peroxidase; D005978:Glutathione