Effect of Tenidap, a novel anti-inflammatory compound on islet lymphocytic infiltration and diabetes incidence in the non obese diabetic (NOD) mouse.
Tenidap, a novel compound inhibiting cyclooxygenase and lipoxygenase, also possessing an inhibitory effect on interleukin-1 secretion by in vitro activated macrophages, has been administered to the non obese diabetic (NOD) mouse to evaluate its action on the induction and progression of insulitis and the diabetes incidence. Animals were allocated to three groups (group A: control group; group B: 12 mg/kg/day Tenidap; group C: 36 mg/kg/day Tenidap); female animals only were followed up to investigate the effect on diabetes incidence. The administration of Tenidap influenced the natural course of insulitis in male NOD mice; thus, at 60 and 100 days of age the mean percentage of infiltrated islets was significantly reduced compared to control animals (p less than 0.02). Moreover the severity of lymphocytic infiltration at 60 days of age was reduced in male mice of group B and C compared to control mice (p less than 0.004 and p less than 0.0001, respectively) whereas at 100 days of age this difference was not significant. However the progression towards severe insulitis in male animals receiving Tenidap was halted compared to control animals. Tenidap had also a significant dose dependent effect at 60 days on the severity of lymphocytic infiltration (group B vs. group C, p less than 0.01). By contrast, this agent had no effect on the degree of insulitis and diabetes incidence in female NOD mice. In both sexes at the end of follow-up a significant reduction in body weight was observed in animals of Group C compared to control animals (p less than 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)
Beales
P E
PE
Department of Diabetes and Metabolism, St Bartholomew's Hospital, London, UK.
Williams
A
A
Krug
J
J
Signore
A
A
Chianelli
M
M
Andreani
D
D
Pozzilli
P
P
D000375:Aging; D000704:Analysis of Variance; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D007211:Indoles / Q000494:pharmacology* / Q000627:therapeutic use; D007515:Islets of Langerhans / Q000187:drug effects / Q000254:growth & development / Q000473:pathology*; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D000078183:Oxindoles
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007211:Indoles; D000078183:Oxindoles; C062866:tenidap