Studies ofd-penicillamine on strain variability and lymph node cellularity in adjuvant arthritis

Abstract

Experiments were performed in order to ascertain the action of D-penicillamine (PA) on adjuvant arthritis (AA) in rats and to develop a quantitative evaluation method for PA-like drugs, using Lewis, SD, and Wistar rats. Rats were inoculated in the tail with 0.6 mg of Mycobacterium butyricum suspended in 0.1 ml of liquid paraffin. PA apparently induced enhancement of arthritis only in Lewis rats with a good reproducibility. The enhancing effect of PA was seen when it was administered during the period from day -7 to day -1, from day 0 to day 6, or from day 14 to day 20. In control group of Lewis and Wistar rats, adjuvant caused a rapid increase in the cell number of lymph nodes just after the inoculation, and also a marked increase in spleen cells coinciding with the development of arthritis. In PA-treated Lewis rats, the cell numbers of lymph nodes and spleen significantly surpassed those of control rats. However, PA induced no difference from control in Wistar rats, which were not sensitive to PA treatment during the course of arthritis. These results indicate that AA in Lewis rats is a good model for evaluating the activities of PA-like drugs and that PA may affect lymphocytes in lymph nodes and spleen and induce severer arthritis in Lewis rats.

Formation of a disulfide protein conjugate of the SH-group-containing metabolite (M-I) of esonarimod (kE-298) and its elimination in rats

“…M-I exists as a tautomeric equilibrium of the thiol form and hydroxytetra-hydrothiophen form (Figure 1). Some anti-rheumatic drugs with immunomodulatory eOE ects contain the thiol moiety, for example d -penicillamine (PEN) (Otomo et al 1981;Nakaike et al 1985) and bucillamine (Fujimura et al 1980;Yamauchi et al 1985), and they can decrease the activity of rheumatic arthritis over a long period. In addition, it is expected that their application at an early stage of arthritis would be more eOE ective (Wilske & Healey 1989).…”