Synergy between tetrandrine and FK506 in prevention of diabetes in BB rats.
Delayed administration of tetrandrine, a novel broad-spectrum anti-inflammatory agent, to BB rats at a dosage schedule of 20 mg kg-1 day-1 from 79 days of age reduced the cumulative incidence of diabetes from 73.1 to 41.7% (p < 0.01). Brief treatment with the potent immunosuppressive agent FK506 at a dosage schedule of 0.5 mg kg-1 day-1 from 79 days of age for 5 days had no significant effect on the cumulative incidence of diabetes (66.7%, p > 0.1). However, the combination of tetrandrine and FK506 in the afore-mentioned dosage schedules reduced the incidence of diabetes to only 3.6% (p < 0.001). These results suggest that the strong synergy between tetrandrine and FK506 may offer a safe and effective therapeutic strategy for the treatment of patients with recent onset or imminent IDDM.
Lieberman
I
I
Division of Endocrinology, Children's Hospital of Pittsburgh, University of Pittsburgh, PA 15213.
Heil
B V
BV
Seow
W K
WK
Thong
Y H
YH
D000470:Alkaloids / Q000627:therapeutic use*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D044182:Benzylisoquinolines; D003922:Diabetes Mellitus, Type 1 / Q000517:prevention & control*; D004357:Drug Synergism; D005260:Female; D008297:Male; D051381:Rats; D011913:Rats, Inbred BB / Q000502:physiology*; D016559:Tacrolimus / Q000627:therapeutic use*
D000470:Alkaloids; D000894:Anti-Inflammatory Agents, Non-Steroidal; D044182:Benzylisoquinolines; C009438:tetrandrine; D016559:Tacrolimus