Indomethacin inhibits thymic involution in mice with streptozotocin-induced diabetes.
Diabetes is chronic disease that is accompanied by a rapid thymus involution. To investigate the factors responsible for thymic involution in a model of STZ-induced diabetes, mice were injected with STZ alone or in combination with the cyclooxygenase 2 inhibitor indomethacin (INDO). Thymus weight, glycemia and serum corticosterone were measured, and apoptosis in thymus and thymocyte cultures was analyzed by flow cytometry. Although earlier studies report that streptozotocin (STZ) is toxic to lymphoid tissues, in our experiments even massive doses of STZ did not negatively affect thymocyte cultures. Cultured thymocytes also seemed unaffected by high glucose concentrations, even after 24 h of exposure. Administration of INDO concomitantly with STZ reduced thymic involution but did not prevent the onset of hyperglycemia or reduce established hyperglycemia. When INDO was given before STZ, the same degree of thymic involution occurred; however, hyperglycemia was reduced, although normoglycemia was not restored. INDO also reduced serum corticosterone. Because thymocytes are known to be sensitive to glucocorticoids, this finding suggests that cyclooxygenase 2 inhibition may retard thymic involution by reducing serum glucocorticoids. In conclusion, our results show that STZ and hyperglycemia are not toxic to thymocytes and that cyclooxygenase 2-mediated mechanisms are involved in thymic involution during diabetes.
Mic
Ani A
AA
Department of Physiology, Victor Babes University of Medicine and Pharmacy, Timisoara, Romania.
Mic
Felix A
FA
Tatu
Calin A
CA
Ionac
Mihai
M
Ordodi
Valentin L
VL
Paunescu
Virgil
V
D000818:Animals; D017209:Apoptosis; D001786:Blood Glucose; D002478:Cells, Cultured; D003345:Corticosterone / Q000097:blood; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000473:pathology*; D005434:Flow Cytometry; D007213:Indomethacin / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D008815:Mice, Inbred Strains; D009929:Organ Size; D015398:Signal Transduction; D013950:Thymus Gland / Q000187:drug effects* / Q000473:pathology
D001786:Blood Glucose; D016861:Cyclooxygenase Inhibitors; D003345:Corticosterone; D007213:Indomethacin