Response of the olfactory bulb antioxidant system following diethyldithiocarbamate (DDTC) administration in rats

J Appl Toxicol. 1999 Jul-Aug;19(4):221-8. doi: 10.1002/(sici)1099-1263(199907/08)19:4<221::aid-jat574>3.0.co;2-3.

Abstract

This study was designed in order to evaluate alterations in the reactive oxygen species (ROS) scavenging system in olfactory bulb, dorsal neocortex and cerebellum for 6 weeks following a single subcutaneous dose (600 mg kg-1) of diethyldithiocarbamate (DDTC) to rats. A single dose of DDTC caused substantial damage to the olfactory epithelium and degeneration within the olfactory bulb. The epithelium regenerates, followed by regeneration in the olfactory bulb. The mean olfactory bulb weight decreased significantly 3 days after DDTC administration and gradually recovered to control values in 6 weeks. The DDTC-induced lesion of the olfactory nerve resulted in significant changes in glutathione (GSH) and antioxidant enzyme activities in olfactory bulb. In contrast, no significant changes were found in either cerebellum or dorsal neocortex. These observations indicate that a single dose of DDTC selectively affected the ROS scavenging system of the olfactory bulb. Moreover, these changes persisted for at least 6 weeks, which includes regeneration and synaptogenesis. Olfactory bulb GSH concentrations decreased significantly by 47 +/- 4%, glutathione reductase activity decreased by 18 +/- 3% and catalase activity increased by 27 +/- 7% over the 6 weeks. Superoxide dismutase activity decreased significantly in olfactory bulb of rats by 32 +/- 6% at 3 days following the lesion and then recovered and increased by 38 +/- 3% at 3 weeks. Olfactory bulb malondialdehyde concentrations were elevated (298 +/- 67%) throughout the post-lesion survival period, although this change did not reach the stringent statistical significance level required in this study. These data suggest that increased ROS flux perturbs the olfactory bulb antioxidant defense system during olfactory nerve regeneration.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antioxidants / metabolism*
  • Catalase / metabolism
  • Cerebellum / drug effects
  • Cerebellum / metabolism
  • Chelating Agents / toxicity*
  • Ditiocarb / toxicity*
  • Epithelium / drug effects
  • Epithelium / metabolism
  • Glutathione / metabolism
  • Glutathione Peroxidase / metabolism
  • Glutathione Reductase / metabolism
  • Injections, Subcutaneous
  • Male
  • Malondialdehyde / metabolism
  • Neocortex / drug effects
  • Neocortex / metabolism
  • Nerve Regeneration / drug effects
  • Nerve Regeneration / physiology
  • Olfactory Bulb / drug effects*
  • Olfactory Bulb / metabolism
  • Olfactory Bulb / pathology
  • Olfactory Nerve / drug effects
  • Olfactory Nerve / metabolism
  • Organ Size / drug effects
  • Oxidoreductases / metabolism*
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species / metabolism*
  • Superoxide Dismutase / metabolism

Substances

  • Antioxidants
  • Chelating Agents
  • Reactive Oxygen Species
  • Malondialdehyde
  • Ditiocarb
  • Oxidoreductases
  • Catalase
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Glutathione Reductase
  • Glutathione