The purpose of this study was to determine the neurotoxicity of two commonly used
herbicides:
picloram and
triclopyr and the
neuroprotective effects of the mitochondria-targeted
antioxidant, SS31. Using mouse
neuroblastoma (N2a) cells and primary neurons from C57BL/6 mice, we investigated the toxicity of these
herbicides, and protective effects of
SS1 peptide against
picloram and
triclopyr toxicity. We measured total
RNA content, cell viability and
mRNA expression of
peroxiredoxins, neuroprotective genes, mitochondrial-encoded electron transport chain (ETC) genes in N2a cells treated with
herbicides and SS31. Using primary neurons from C57BL/6 mice, neuronal survival was studied in neurons treated with
herbicides, in neurons pretreated with SS31 plus treated with
herbicides, neurons treated with SS31 alone, and untreated neurons. Significantly decreased total
RNA content, and cell viability in N2a cells treated with
picloram and
triclopyr were found compared to untreated N2a cells. Decreased
mRNA expression of neuroprotective genes, and ETC genes in cells treated with
herbicides was found compared to untreated cells. Decreased
mRNA expression of
peroxiredoxins 1-6 in N2a cells treated with
picloram was found, suggesting that
picloram affects the
antioxidant enzymes in N2a cells. Immunofluorescence analysis of primary neurons revealed that decreased neuronal branching and degenerating neurons in neurons treated with
picloram and
triclopyr. However, neurons pretreated with SS31 prevented degenerative process caused by
herbicides. Based on these results, we propose that
herbicides--
picloram and
triclopyr appear to damage neurons, and the
SS31 peptide appears to protect neurons from
herbicide toxicity.