Role of 12/15-lipoxygenase in nitrosative stress and peripheral prediabetic and diabetic neuropathies

Roman Stavniichuk, Viktor R. Drel, Hanna Shevalye, Igor Vareniuk, Martin J. Stevens, Jerry L. Nadler, Irina G. Obrosova

Research output: Contribution to journalArticlepeer-review

46 Scopus citations


This study evaluated the role of 12/15-lipoxygenase, which converts arachidonic acid to 12(S)- and 15(S)-hydroxyeicosatetraenoic acids, in nitrosative stress in the peripheral nervous system and peripheral prediabetic and diabetic neuropathies. The experiments were performed in C57BL6/J mice made diabetic with streptozotocin or fed a high-fat diet and in human Schwann cells cultured in 5.5 or 30mM glucose. 12/15-Lipoxygenase overexpression and activation were present in sciatic nerve and spinal cord of diabetic and high-fat diet-fed mice, as well as in human Schwann cells cultured in high concentrations of D-, but not L-glucose. 12/15-Lipoxygenase inhibition by cinnamyl-3,4-dihydroxy-α-cyanocinnamate (8mg kg-1 day-1 sc, for 4weeks after 12weeks without treatment) alleviated the accumulation of nitrated proteins in the sciatic nerve and spinal cord, and large and small nerve fiber dysfunction, but not intraepidermal nerve fiber loss. 12/15-Lipoxygenase gene deficiency alleviated nitrosative stress and nerve conduction deficit, but not small sensory fiber neuropathy, in high-fat diet-fed mice. In conclusion, 12/15-lipoxygenase is implicated in nitrosative stress and peripheral neuropathy in mouse models of type 1 and early type 2 diabetes. Its presence in human Schwann cells and upregulation by high glucose suggest a potential involvement in human disease.

Original languageEnglish (US)
Pages (from-to)1036-1045
Number of pages10
JournalFree Radical Biology and Medicine
Issue number6
StatePublished - Sep 2010
Externally publishedYes


  • 12(S)-Hydroxyeicosatetraenoic acid
  • 12/15-Lipoxygenase
  • Free radicals
  • Human Schwann cell
  • Intraepidermal nerve fiber density
  • Nerve conduction
  • Nitrosative stress
  • Peripheral diabetic neuropathy
  • Tactile allodynia
  • Thermal algesia

ASJC Scopus subject areas

  • Physiology (medical)
  • Biochemistry


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