Altered glycine transport by cerebral tissue and decreased Na⁺ and Ca⁺⁺ pump activities during organophosphorus‐ester–induced delayed neurotoxicity development period

Abstract

Uptake of [U-14C] glycine during the organophosphorus-ester-induced delayed neurotoxicity (OPIDN) development period was studied. Diisopropyl fluorophosphate (DFP), a delayed neurotoxic organophosphorus ester was administered to adult rats and hens. Results showed a decreased accumulation of glycine in hen cerebral cortex slices during the delayed neurotoxicity development period. An altered sensitivity toward transport inhibitors 2,4-dinitrophenol and ouabain was observed in DFP-treated hens. An altered neuronal membrane function during the OPIDN development period is reported in the present work. Brain Na+, K(+)-ATPase and Ca(++)-ATPase activities decreased during the neurotoxicity development period. The decrease in Ca(++)-ATPase activity persisted in hens until the complete development of neurotoxic symptoms. Decreased Ca++ pump activity is correlated with altered membrane function during OPIDN.

Impaired Mitochondrial Functions in Organophosphate Induced Delayed Neuropathy in Rats

“…The steps from NTE inhibition to development of neuropathy are not clear. In addition to NTE inhibition, cytoskeleton abnormalities (Abou-Donia 1995), altered membrane function (Sharma and Bhattacharya 1995), induction of c-jun (Damodaran et al 2000), alterations in dopaminergic system (Choudhary et al 2002), aberrant activation of CDK5 (Wang et al 2006), activation of MAP Kinase (Hargreaves et al 2006), and CREB (Damodaran et al 2002) have been observed in experimental models of OPIDN.…”

Increased oxidative stress is associated with the development of organophosphate-induced delayed neuropathy

“…11 However, NTE activity returns to normal well before the onset of clinical and morphological signs, 11 suggesting that the precise biochemical mechanism involved in the development of OPIDN is not well understood. Besides, studies done with experimental model of OPIDN have shown cytoskeleton abnormalities, 12 alterations in dopaminergic system, 13,14 altered membrane function, 15 aberrant activation of cyclin-dependent kinase 5 (CDK5), 16 activation of mitogen-activated protein (MAP) kinase 17 and cAMP-response element binding (CREB), 18 induction of c-jun, 19 decreased ATP production, impaired mitochondrial functions 20 and mitochondrial integrity. 21 Oxidative stress has long been linked to the neuronal cell death that is associated with many neurodegenerative conditions.…”