Chronic treatment with d-chiro-inositol prevents autonomic and somatic neuropathy in STZ-induced diabetic mice

Authors

  • V. X. Farias,

    1. Department of Physiology and Pharmacology, Superior Institute of Biomedical Sciences, Fortaleza, Ceará, Brazil
    Search for more papers by this author
  • F. H. P. Macêdo,

    1. Department of Physiology and Pharmacology, Superior Institute of Biomedical Sciences, Fortaleza, Ceará, Brazil
    2. Electrophysiology Laboratory, Superior Institute of Biomedical Sciences, Fortaleza, Ceará, Brazil
    Search for more papers by this author
  • M. B. Oquendo,

    1. Department of Physiology and Pharmacology, Superior Institute of Biomedical Sciences, Fortaleza, Ceará, Brazil
    2. Electrophysiology Laboratory, Superior Institute of Biomedical Sciences, Fortaleza, Ceará, Brazil
    Search for more papers by this author
  • A. R. Tomé,

    1. Department of Physiology and Pharmacology, Superior Institute of Biomedical Sciences, Fortaleza, Ceará, Brazil
    Search for more papers by this author
  • S. N. Báo,

    1. Electron Microscopy Laboratory, Institute of Biological Sciences, University of Brasilia, Brasilia, Distrito Federal, Brazil
    2. Institute of Biological Sciences, Universidade de Brasília, Fortaleza, Ceará, Brazil
    Search for more papers by this author
  • D. O. S. Cintra,

    1. Electron Microscopy Laboratory, Institute of Biological Sciences, University of Brasilia, Brasilia, Distrito Federal, Brazil
    2. Institute of Biological Sciences, Universidade de Brasília, Fortaleza, Ceará, Brazil
    Search for more papers by this author
  • C. F. Santos,

    1. Department of Physiology and Pharmacology, Superior Institute of Biomedical Sciences, Fortaleza, Ceará, Brazil
    Search for more papers by this author
  • A. A. C. Albuquerque,

    1. Department of Physiology and Pharmacology, Superior Institute of Biomedical Sciences, Fortaleza, Ceará, Brazil
    2. Electrophysiology Laboratory, Superior Institute of Biomedical Sciences, Fortaleza, Ceará, Brazil
    Search for more papers by this author
  • D. B. Heimark,

    1. Department of Pharmacology, School of Medicine, University of Virginia, Charlottesville, VA, USA
    Search for more papers by this author
  • J. Larner,

    1. Department of Pharmacology, School of Medicine, University of Virginia, Charlottesville, VA, USA
    Search for more papers by this author
  • M. C. Fonteles,

    1. Department of Physiology and Pharmacology, Superior Institute of Biomedical Sciences, Fortaleza, Ceará, Brazil
    2. Biology and Health Sciences Center, Mackenzie Presbyterian University, São Paulo, Brazil
    Search for more papers by this author
  • J. H. Leal-Cardoso,

    1. Department of Physiology and Pharmacology, Superior Institute of Biomedical Sciences, Fortaleza, Ceará, Brazil
    2. Electrophysiology Laboratory, Superior Institute of Biomedical Sciences, Fortaleza, Ceará, Brazil
    Search for more papers by this author
  • N. R. F. Nascimento

    Corresponding author
    1. Department of Physiology and Pharmacology, Superior Institute of Biomedical Sciences, Fortaleza, Ceará, Brazil
    2. Department of Physiology and Pharmacology, State University of Ceará, Fortaleza, Ceará, Brazil
    3. Department of Endocrinology, University of Virginia, Charlottesville, VA, USA
    Search for more papers by this author

Prof. Nilberto Robson Falcão do Nascimento, Laboratório de Farmacologia Cardiovascular, Instituto Superior de Ciências Biomédicas-ISCB, Universidade Estadual do Ceará, Av. Paranjana, 1700, Campus do Itaperi, CEP 60740-00, Fortaleza, Ceará, Brazil. E-mail: nilberto.nascimento@gmail.com

Abstract

Aim:d-chiro-inositol (DCI) has been shown to prevent and reverse endothelial dysfunction in diabetic rats and rabbits. The present study evaluates the preventive effect of DCI on experimental diabetic neuropathy (DN).

Methods: Streptozotocin-induced (STZ) diabetic mice were treated by oral gavage for 60 days with DCI (20 mg/kg/12 h) or saline (NaCl 0.9%; 0.1 ml/10 g/12 h; Diab) and compared with euglycaemic groups treated with saline (0.1 ml/10 g/12 h; Eugly). We compared the response of the isolated sciatic nerve, corpora cavernosa or vas deferens to electrical stimulation.

Results: The electrically evoked compound action potential of the sciatic nerve was greatly blunted by diabetes. The peak-to-peak amplitude (PPA) was decreased from 3.24 ± 0.7 to 0.9 ± 0.2 mV (p < 0.05), the conduction velocity (CV) of the first component was reduced from 46.78 ± 4.5 to 26.69 ± 3.8 ms (p < 0.05) and chronaxy was increased from 60.43 ± 1.9 to 69.67 ± 1.4 ms (p < 0.05). These parameters were improved in nerves from DCI-treated mice (p < 0.05). PPA in the DCI group was 5.79 ± 0.8 mV (vs. 0.9 ± 0.2 mV—Diab; p < 0.05) and CV was 45.91 ± 3.6 ms (vs. 26.69 ± 3.8 ms—Diab; p < 0.05). Maximal relaxation of the corpus cavernosum evoked by electrical stimulation (2–64 Hz) in the Diab group was 36.4 ± 3.8% compared to 65.4 ± 2.8% in Eugly and 59.3 ± 5.5% in the DCI group (p < 0.05). Maximal contraction obtained in the vas deferens was 38.0 ± 9.2% in Eugly and 11.5 ± 2.6% in Diab (decrease of 69.7%; p < 0.05), compared to 25.2 ± 2.3% in the DCI group (p < 0.05 vs. diabetic). Electron microscopy of the sciatic nerves showed prevention of neuronal damage.

Conclusions: DCI has a neuroprotective action in both autonomic and somatic nerves in STZ-induced DN.

Ancillary