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

Abstract

Organophosphate-induced delayed neuropathy (OPIDN) is a progressive neuropathic disorder that manifests in days to weeks following exposure to an acute dose of organophosphates. The precise mechanism involved in the development of OPIDN is not clear as it develops after many days of the cessation of cholinergic crisis. The present study has been designed to understand the role of oxidative stress in the development of OPIDN, wherein neuropathy was developed by the administration of acute dose of monocrotophos (MCP) or dichlorvos (2,2-dichlorovinyl dimethyl phosphate (DDVP)) to rats. Significant motor deficits in terms of reduced spontaneous locomotor activity and performance on narrow beam test were observed after 14 days of exposure to MCP or DDVP, which persisted even on day 28, suggesting the development of OPIDN. Rats with OPIDN also exhibited an increase in malondialdehyde levels along with a decrease in thiol content in cerebral cortex, cerebellum and brain stem. Concomitantly, the activities of antioxidant enzymes, superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase were reduced in the three brain regions. The biochemical and functional changes were associated with histological alterations in the brain regions studied. The results clearly indicate that the development of OPIDN is mediated in part through an increased oxidative stress and suggest that the strategies aimed at restoration of antioxidant capacity may be beneficial for the individuals with OPIDN-like symptoms.

RETRACTED ARTICLE: Apelin-13 Prevents the Delayed Neuropathy Induced by Tri-ortho-cresyl Phosphate Through Regulation the Autophagy Flux in Hens

“…So OPIDN in hens can not be completely simulated in human. OPIDN in mammals has been also successfully established in rats [41,42]. So in our further research, we will observe the effect of Apelin-13 on the OPIDN in rats.…”

“…This study provides novel evidence that application of Apelin-13 for OPIDN and Apelin-13 may be a potential drug in clinical applications for OPIDN. OPIDN is characterized by ataxia that progresses to paralysis concurrent with a central-peripheral distal axonopathy after a delay period of 1-3 weeks following exposure to OP [34]. TOCP is a well-studied organophosphate which causes the OPIDN.…”

“…Typical signs and symptoms of OPIDN include tingling of the hands and feet, followed by sensory loss, progressive muscle weakness and flaccidity of the distal skeletal muscles of the lower and upper extremities and ataxia [3][4][5]. In pathology, OPIDN is classified as a centralperipheral sensorimotor axonopathy, which is characterized by distal axonal degeneration in spinal cord and peripheral nerves and swollen axons containing aggregations of microtubules, neurofilaments, smooth endoplasmic reticulum and multivesicular vesicles [6,7]. At present, there is a lack of effective means to treat OPIDN, so it is very important to find new effective therapy means to treat OPIDN.…”

Oxaliplatin Neurotoxicity Involves Peroxisome Alterations. PPARγ Agonism as Preventive Pharmacological Approach

“…Brain of aged patients showed a reduced catalase functionality [55], similarly catalase activity was affected in a rat model of Parkinson’s disease [56]. Catalase impairment was also described in neuropathic conditions since decreased catalase efficiency was described in sciatic nerve of rats affected by diabetic neuropathy [57] as well as in brain regions of animals with delayed neuropathy induced by organophosphate [58]. On the other hand, the oxidative unbalance of these painful conditions has never been associated with peroxisome alterations.…”

Protective effect of crocin on diazinon induced vascular toxicity in subchronic exposure in rat aortaex-vivo

“…In addition to the inhibition of acetylcholine esterase, DZN causes remarkable atropine-insensitive hypotension in rats when administered intravenously in lethal doses and exerts vasorelaxant actions in endothelium-denuded rat aorta (Kojima et al, 1993). Moreover animal studies showed that DZN increases oxygen free radicals (Shadnia et al, 2005) and oxygen free radicals play a role in OPs toxicity including delayed neuropathy (Masoud & Sandhir, 2012;Ogutcu et al, 2006), a progressive neuropathic disorder that develops after many days of the cessation of cholinergic crisis. Furthermore some studies showed that cardiovascular toxicity induced by OPs could be related to the oxidative stress (Kumar & Jugdutt, 2003), and antioxidants can suppress toxicity (Guney et al, 2007;Kumar & Jugdutt, 2003).…”