Neuroprotective mechanisms induced in acute organophosphate poisoning.

Amajad Iqbal, Kazi (2010) Neuroprotective mechanisms induced in acute organophosphate poisoning. Doctoral thesis, Christian Medical College, Vellore.


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During the first half of the nineteenth century an estimated 2-5 million cases of pesticide poisoning occurred world-wide of which 400,000 were fatal. WHO estimates around 3 million people are treated for the effects of organophosphate poisoning (OPP) (1) with more than 200,000 deaths each year (2). OPP can occur in a variety of situations and can be accidental or suicidal. Acute OPP is a major cause of death in many middle and low-income countries where the problems associated with pesticide poisoning are significant. Studies from Asia have documented self-poisoning with pesticides as a predominant method of suicide. In Sri Lanka, China and Malaysia more than 60% of all suicides in rural areas are from organophosphate (OP) pesticide poisoning (3). OP pesticides are commonly consumed suicidal agents in Pakistan (4) and South East Asia. Acute OPP is a major problem in South India. The incidence of self-harm with organophosphate pesticides is very high in young women in South India and accounts for 50-75% of all deaths (5). OP pesticides consumed in intentional self-harm are determined by their availability in different regions. The impulsive acts of self-harm in rural India to a largely extent reflect socioeconomically deprived households. In conclusion the study showed that organophosphate pesticide poisoning induced different levels of brain damage through glutamate excitotoxicity in rodents. The protective response to toxicity was by both GABA inhibition of glutamate induced convulsions and mechanisms that supported anti-oxidation and neuronal survival. Neuroprotective responses were region specific and most active in regions of high cholinergic and glutamatergic systems such as the striatum and hippocampus. The cortex and cerebellum were less susceptible to MCP induced damage because of low glutamate involvement and protection from global effects of poisoning by antioxidants and antioxidative stress response proteins. Chronic sound stress regulation of the rodent nervous system is effective in protecting the brain against organophosphate pesticide poisoning. The studies in the thesis have elucidated endogenous neuroprotective mechanisms that lead to effective recovery from acute toxicity of an OP pesticide in rodents. Studies are now needed to determine whether these systems also occur following acute severe OP pesticide poisoning in humans. This would allow for the development of treatment interventions that target these pathways. Such treatments would not be based on OP inhibited AChE reactivation and therefore may be more appropriate for many severely OP poisoned patients.

Item Type: Thesis (Doctoral)
Uncontrolled Keywords: Acute organophosphate poisoning; Neuroprotective mechanisms;
Subjects: MEDICAL > Neurology
Depositing User: Devi S
Date Deposited: 21 Jun 2017 07:36
Last Modified: 22 Jun 2017 05:27

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