alexa Dissection of metabolic, vascular, and nerve conduction interrelationships in experimental diabetic neuropathy by cyclooxygenase inhibition and acetyl-L-carnitine administration.
Infectious Diseases

Infectious Diseases

Journal of AIDS & Clinical Research

Author(s): PopBusui R, Marinescu V, Van Huysen C, Li F, Sullivan K, , PopBusui R, Marinescu V, Van Huysen C, Li F, Sullivan K,

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Abstract Alterations in cyclooxygenase (COX) pathway activity have been implicated in the pathogenesis of experimental diabetic neuropathy (EDN). These studies explore the relationships between COX-mediated and acetyl-L-carnitine (ALC)-sensitive defects that contribute to functional, metabolic, and vascular abnormalities of EDN. The effects of nonselective COX inhibition with flurbiprofen were contrasted with selective COX-2 inhibition with meloxicam, administered alone and in combination with ALC in nondiabetic (ND) and streptozotocin-induced diabetic (STZ-D) rats. Flurbiprofen treatment of ND rats replicated many of the biochemical and physiological abnormalities of EDN, i.e., reduced motor nerve conduction velocity (MNCV), total and endoneurial nerve blood flow (NBF), Na,K-ATPase activity, and myo-inositol (MI) and taurine content. In STZ-D rats, however, flurbiprofen paradoxically prevented endoneurial NBF deficits but not MNCV slowing. Coadministration of 50 mg x kg(-1) x day(-1) ALC prevented reductions in MNCV, Na,K-ATPase activity, and endoneurial NBF in flurbiprofen-treated ND and STZ-D rats. In contrast, selective COX-2 inhibition with meloxicam was without effect on MNCV, NBF, or MI content in ND rats and prevented MNCV slowing and NBF deficits in STZ-D rats. Western blot analysis showed unchanged sciatic nerve COX-1 protein but increased COX-2 protein abundance in STZ-D versus ND rats. These results imply 1) a tonic role of the COX-1 pathway in the regulation of nerve osmolytes and Na,K-ATPase activity and the maintenance of NBF in ND animals and 2) activation of the COX-2 pathway as an important mediator of NBF and MNCV deficits in EDN.
This article was published in Diabetes and referenced in Journal of AIDS & Clinical Research

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