Peripheral nerve dysfunction in experimental diabetes is mediated by cyclooxygenase-2 and oxidative stress.
Glucose-mediated oxidative stress and alterations in cyclooxygenase (COX) pathway activity with secondary deficits of endoneurial perfusion have been implicated in the pathogenesis of experimental diabetic neuropathy (EDN). We have previously reported that activation of the COX-2 pathway is an important mediator of neurochemical and neurovascular defects in EDN in a rat model. Considering that chemical COX inhibition may exert other pharmacological effects in addition to inhibition of COX activity, the aim of this study was to explore the role of COX-2 in experimental diabetic neuropathy, using a COX-2 knockout mouse model. Here we provide evidence that COX-2 inactivation had a protective effect against diabetes-induced motor and sensory nerve conduction slowing and impaired nerve antioxidative defense that were clearly manifest in the wild-type (COX-2(+/+)) diabetic mice. These preliminary data support the role of the activation of the COX-2 pathway in mediating sensory and motor nerve conduction velocity deficits in EDN. These findings also suggest that the COX-2 pathway seems to be an important modulator of oxidative stress in EDN.
Kellogg
Aaron P
AP
Medical College of Ohio, Department of Medicine and Physiology, Toledo, OH, USA.
Pop-Busui
Rodica
R
D000475:Alkenes / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001786:Blood Glucose; D001835:Body Weight / Q000187:drug effects / Q000235:genetics; D051546:Cyclooxygenase 2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications / Q000201:enzymology / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology*; D004789:Enzyme Activation / Q000235:genetics; D005978:Glutathione / Q000378:metabolism; D006900:Hydroxylation; D015227:Lipid Peroxidation / Q000187:drug effects / Q000235:genetics; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D018384:Oxidative Stress; D010525:Peripheral Nerves / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology*; D011453:Prostaglandins / Q000378:metabolism; D013311:Streptozocin / Q000494:pharmacology
D000475:Alkenes; D000975:Antioxidants; D001786:Blood Glucose; D011453:Prostaglandins; D008315:Malondialdehyde; D013311:Streptozocin; D051546:Cyclooxygenase 2; D005978:Glutathione