Evaluation of the peroxynitrite decomposition catalyst Fe(III) tetra-mesitylporphyrin octasulfonate on peripheral neuropathy in a mouse model of type 1 diabetes

  • Authors:
    • Viktor R. Drel
    • Pal Pacher
    • Igor Vareniuk
    • Ivan A. Pavlov
    • Olga Ilnytska
    • Valeriy V. Lyzogubov
    • Seth R. Bell
    • John T. Groves
    • Irina G. Obrosova
  • View Affiliations

  • Published online on: December 1, 2007     https://doi.org/10.3892/ijmm.20.6.783
  • Pages: 783-792
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Abstract

Whereas the important role of free radicals in diabetes-associated complications is well established, the contributions of the highly reactive oxidant peroxynitrite have not been properly explored. The present study used a pharmacological approach to evaluate the role of peroxynitrite in peripheral diabetic neuropathy. Control and STZ-diabetic mice were maintained with or without treatment with the potent peroxynitrite decomposition catalyst Fe(III) tetramesitylporphyrin octasulfonate (FeTMPS), at doses of 5 or 10 mg/kg/day in the drinking water for 3 weeks after an initial 3 weeks without treatment. Mice with a 6-week duration of diabetes developed clearly manifest motor (MNCV) and sensory nerve conduction velocity (SNCV) deficits, thermal hypoalgesia (paw withdrawal, tail-flick, and hot plate tests), mechanical hypoalgesia (tail pressure Randall-Sellito test), tactile allodynia (flexible von Frey filament test), and ≈44% loss of intraepidermal nerve fibers. They also had increased nitrotyrosine and poly(ADP-ribose) immunofluorescence in sciatic nerve, grey matter of the spinal cord, and dorsal root ganglion neurons. FeTMPS treatment alleviated or essentially corrected (at a dose of 10 mg/kg/day) MNCV and SNCV deficits, and was associated with less severe small sensory nerve fiber dysfunction and degeneration. Nitrotyrosine and poly(ADP-ribose) immunofluorescence in sciatic nerve, spinal cord, and dorsal root ganglion neurons in peroxynitrite decomposition catalyst-treated diabetic mice was markedly reduced. In conclusion, peroxynitrite contributes to large motor, large sensory, and small sensory fiber neuropathy in streptozotocin-diabetic mice. The findings provide rationale for development of potent peroxynitrite decomposition catalysts for the treatment of diabetic neuropathy.

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December 2007
Volume 20 Issue 6

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Drel VR, Pacher P, Vareniuk I, Pavlov IA, Ilnytska O, Lyzogubov VV, Bell SR, Groves JT and Obrosova IG: Evaluation of the peroxynitrite decomposition catalyst Fe(III) tetra-mesitylporphyrin octasulfonate on peripheral neuropathy in a mouse model of type 1 diabetes. Int J Mol Med 20: 783-792, 2007
APA
Drel, V.R., Pacher, P., Vareniuk, I., Pavlov, I.A., Ilnytska, O., Lyzogubov, V.V. ... Obrosova, I.G. (2007). Evaluation of the peroxynitrite decomposition catalyst Fe(III) tetra-mesitylporphyrin octasulfonate on peripheral neuropathy in a mouse model of type 1 diabetes. International Journal of Molecular Medicine, 20, 783-792. https://doi.org/10.3892/ijmm.20.6.783
MLA
Drel, V. R., Pacher, P., Vareniuk, I., Pavlov, I. A., Ilnytska, O., Lyzogubov, V. V., Bell, S. R., Groves, J. T., Obrosova, I. G."Evaluation of the peroxynitrite decomposition catalyst Fe(III) tetra-mesitylporphyrin octasulfonate on peripheral neuropathy in a mouse model of type 1 diabetes". International Journal of Molecular Medicine 20.6 (2007): 783-792.
Chicago
Drel, V. R., Pacher, P., Vareniuk, I., Pavlov, I. A., Ilnytska, O., Lyzogubov, V. V., Bell, S. R., Groves, J. T., Obrosova, I. G."Evaluation of the peroxynitrite decomposition catalyst Fe(III) tetra-mesitylporphyrin octasulfonate on peripheral neuropathy in a mouse model of type 1 diabetes". International Journal of Molecular Medicine 20, no. 6 (2007): 783-792. https://doi.org/10.3892/ijmm.20.6.783