4-iodophenyl isothiocyanate: a neuroprotective compound.

Abstract

PURPOSE:

Naturally occurring isothiocyanates (ITCs) are known to possess chemopreventive and neuroprotective properties. Our objective was to study the synthetic ITC 4-iodophenyl isothiocyanate (4-IPITC) in different models of neurodegeneration.

METHODS:

In vitro, we exposed primary cortical neurons to various insults such as excessive glutamate exposure, oxygen-glucose deprivation, oxidative stress and 1-methyl-phenylpyridinium (MPP+). In vivo, experimental autoimmune encephalomyelitis (EAE) was induced in dark agouti rats treated with 4-IPITC in 3 different concentrations (10, 20 and 40 mg/kg), orally for 28 days. In a Parkinson's model, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was injected in mice pretreated with 4-IPITC (5 mg/kg, orally) for 1 week. Nest building behavior at day 1, 3 and 6 after MPTP injection was assessed along with dopamine and metabolites, and tyrosine hydroxylase (TH) staining on termination day 6.

RESULTS:

4-IPITC successfully reduced cell death in all in vitro assays. Moreover, in two independent neurite outgrowth assays the compound showed neurotrophic properties. In the EAE study, 4-IPITC significantly delayed the day of onset and decreased the cumulative EAE score. Although the number of animals in this MPTP study was limited, 4-IPITC showed potential for dampening toxicity.

CONCLUSIONS:

Taken together, our in vitro findings suggest robust neuroprotective and neurotrophic properties of 4-IPITC, which was confirmed in two in vivo models of neurodegeneration.

• Authors: Anja Wellejus, Heidi Elbrønd-Bek, Nicholas M Kelly, Morten S Weidner, Signe H Jørgensen
• Journal: Restorative neurology and neuroscience (Restor Neurol Neurosci) Vol. 30 Issue 1 Pg. 21-38 ( 2012) ISSN: 1878-3627 [Electronic] Netherlands
• PMID: 22082767 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Dopamine Plasma Membrane Transport Proteins
• Enzyme Inhibitors
• Excitatory Amino Acid Agonists
• Herbicides
• Iodobenzenes
• Isothiocyanates
• Neuroprotective Agents
• Peroxides
• 4-iodophenylisothiocyanate
• Glutamic Acid
• N-Methylaspartate
• L-Lactate Dehydrogenase
• Monoamine Oxidase
• Glucose
• 1-Methyl-4-phenylpyridinium

Topics

• 1-Methyl-4-phenylpyridinium (toxicity)
• Analysis of Variance
• Animals
• Cells, Cultured
• Cerebral Cortex (cytology)
• Dopamine Plasma Membrane Transport Proteins (metabolism)
• Dose-Response Relationship, Drug
• Embryo, Mammalian
• Encephalomyelitis, Autoimmune, Experimental (drug therapy, etiology, pathology)
• Enzyme Inhibitors (pharmacology)
• Excitatory Amino Acid Agonists (pharmacology)
• Glucose (deficiency)
• Glutamic Acid (pharmacology)
• Herbicides (toxicity)
• Hypoxia (drug therapy)
• Iodobenzenes (pharmacology)
• Isothiocyanates (pharmacology)
• L-Lactate Dehydrogenase (metabolism)
• Monoamine Oxidase (metabolism)
• N-Methylaspartate (pharmacology)
• Neurites (drug effects)
• Neuroglia (drug effects)
• Neurons (cytology, drug effects)
• Neuroprotective Agents (pharmacology)
• Peroxides (pharmacology)
• Protein Binding (drug effects)
• Rats
• Rats, Wistar