Spin trapping agent phenyl N-tert-butylnitrone protects against the onset of drug-induced insulin-dependent diabetes mellitus.
Insulin-dependent diabetes mellitus is an autoimmune disease believed to be caused by an inflammatory process in the pancreas leading to selective destruction of the beta-cells. Cytokines and nitric oxide (NO) have been shown to be involved in this destruction. Phenyl N-tert-butylnitrone (PBN) has demonstrated protective effects against several pathological conditions including ischemia-reperfusion injury and endotoxin-induced shock. We report here that PBN co-administration can prevent the onset of the STZ-induced diabetes in mice. PBN co-treatment inhibited the streptozotocin (STZ)-induced hyperglycemia, the elevation in the level of glycated hemoglobin and weight loss in the treated mice. Histological observations indicated destruction of B-cells in the STZ-treated animals and its prevention by PBN co-treatment. EPR spin trapping experiments in the pancreas indicated the in vivo formation of NO in STZ-treated animals and its attenuation by PBN treatment.
Tabatabaie
T
T
Free Radical Biology and Aging Research Program, Oklahoma Medical Research Foundation, Oklahoma City 73104, USA. Tahereh-Tabatabaie@omrf.uokhsc.edu
Kotake
Y
Y
Wallis
G
G
Jacob
J M
JM
Floyd
R A
RA
D000818:Animals; D003497:Cyclic N-Oxides; D003921:Diabetes Mellitus, Experimental / Q000517:prevention & control*; D003922:Diabetes Mellitus, Type 1 / Q000517:prevention & control*; D004578:Electron Spin Resonance Spectroscopy; D006442:Glycated Hemoglobin / Q000032:analysis; D006943:Hyperglycemia / Q000517:prevention & control; D007515:Islets of Langerhans / Q000033:anatomy & histology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009589:Nitrogen Oxides / Q000627:therapeutic use*; D019097:Spin Trapping; D013311:Streptozocin; D015431:Weight Loss / Q000187:drug effects
D003497:Cyclic N-Oxides; D006442:Glycated Hemoglobin; D009589:Nitrogen Oxides; D013311:Streptozocin; C029217:phenyl-N-tert-butylnitrone