Suppression of adjuvant-induced arthritis in the rat by gold sodium thiomalate.

Abstract

Gold salts have been used in the treatment of rheumatoid arthritis for nearly 40 years. Their effectiveness, while not consistent, has been well established (Freyberg, 1966) and their use continues. Recently, conflicting results concerning the effectiveness of gold salts on adjuvant arthritis in rats have been reported (Newbould, 1963;Jessop and Currey, 1968). Adjuvant arthritis, a crippling deformity resulting from diffuse connective tissue involvement, is considered by some authorities to be the best available experimental model of rheumatoid arthritis because of its strong clinical and pathological siinilarities to the human disease (Pearson, 1963) HINDLEG VOLUME This was determined by a modified method of VanArman, Begany, Miller, and Pless (1965). On the day of assay (3 to 4 hours after drug administration), the hindlegs were immersed to the anatomical hairline into a mercury reservoir. The mercury column was connected to a Statham pressure transducer (Model P23BB, 0-5 cm. Hg.). The output from the transducer was led through an amplifier to a Hewlett-Packard digital voltmeter (Model HP-3440A), and a high gain/auto range unit (Model 3443A), and finally to a digital recorder (Model J74562A). The digital recordings were calibrated, and a linear relationship between MV and ML was obtained by placing cylinders of known volumes into the mercury reservoir. ARTHRITIC SCOREThe severity of secondary lesions in the uninjected hindleg was graded 0 to 4, depending upon the area and magnitude of involvement. DRUG ADMINISTRATIONGold sodium thiomalate (Myocrysine() was prepared at various concentrations in 0 5 per cent. benzyl alcohol and injected intramuscularly (right thigh) in a volume of 0 5 ml./kg. The drug was administered once daily (exclusive of weekend days indicated in the text) starti either on Day 0 or one week before adjuvant injection and continuing until the termination of the experiment (Day 16). Control animals were treated in an identical manner using 0 5 per cent. benzyl alcohol for the intramuscular injections. The benzyl alcohol solution was prepared with either 0 * 9 per cent. saline or water for injection.The level of significant difference between hindleg volumes, arthritic score, and body weight of drug-treated and control groups was determined by the Student's 't' test. SERUM GOLD LEVELBlood samples were obtained after the decapitation of the adjuvant arthritic rats. 0 5 mJ. aliquot of serum was diluted to 3 0 ml. with distilled water and absorption measured in a Perkin-Elmer Model 303 atomic absorption spectrophotometer (wavelength 243 -3 mjt slit 4,

Blood changes in experimental arthritis in two types of genetically different rats

“…This is mainly because the rat model is suppressed by numerous drugs used in the treatment of the human disease, as for example glucocorticoids, salicylates and other analgesics (Newbould, 1963;Winter & Nuss, 1966;Graeme, Fabry & Sigg, 1966), and immunosuppressive agents (Ward, Cloud, Krawitt & Jones, 1964). However, reports that gold salts improve adjuvant arthritis (Newbould, 1963;Walz, Di Martino & Misher, 1971) were not confirmed by Jessop & Currey (1968).…”

The antiinflammatory effect in rats of Chieh‐pu‐warn, a traditional chinese herbal preparation

“…Adjuvant-induced edematous response or polyarthritis is the most frequently investigated chronic inflammatory model and is extensively used in rats by pathologists and pharmacologists (Walz et al, 1971). Since Freund's complete adjuvant-induced edematous formation produced a local inflamed swelling which reaches its maximal response during the 4-5 days.…”

Mechanisms Underlying the Suppression of Adjuvant‐Induced Arthritis by 6‐Mercaptopurine

“…Subsequent studies on the histopathology (19)(20)(21)(22) and on the response to antiinflammatory and immunosuppressive drugs (14, [23][24][25][26] revealed close similarities between this experimental disease and rheumatoid arthritis. It is generally accepted that adjuvant arthritis is an immunologic disease, even though the precise responsible immunogen has not been clearly established (3,6,27).…”

“…It has been shown that modification of adjuvant arthritis as a result of immunosuppression can be differentiated from that due to antiinflammatory effects by varying the drug dosing regimen (25,26). A course of 12 daily doses of immunosuppressive drugs (azathioprine 30 mg/kg PO, cyclophosphamide 10 mg/kg PO), beginning on the day of adjuvant injection was reported by Perper et a1 (26) to prevent the development of the secondary lesions measured on day 21.…”