The role of multifunctional drug therapy as an antidote to combat experimental subacute neurotoxicity induced by organophosphate pesticides

Abstract

Organophosphate pesticides are used in agriculture where they are associated with numerous cases of intentional and accidental misuse. These toxicants are potent inhibitors of cholinesterases leading to a massive build-up of acetylcholine which induces an array of deleterious effects, including convulsions, oxidative damage and neurobehavioral deficits. Antidotal therapies with atropine and oxime yield a remarkable survival rate, but fail to prevent neuronal damage and behavioral problems. It has been indicated that multifunction drug therapy with potassium channel openers, calcium channel antagonists and antioxidants (either single-agent therapy or combination therapy) may have the potential to prevent cell death and/or slow down the processes of secondary neuronal damage. The aim of the present study, therefore, was to make a relative assessment of the potential effects of nicorandil (2 mg/kg), clinidipine (10 mg/kg), and grape seed proanthocyanidin (GSPE) extract (200 mg/kg) individually against subacute chlorpyrifos induced toxicity. The test drugs were administered to Wistar rats 2 h after exposure to Chlorpyrifos (CPF). Different behavioral studies and biochemical estimation has been carried in the study. The results showed that chronic administration of CPF significantly impaired learning and memory, along with motor coordination, and produced a marked increase in oxidative stress along with significantly reduced acetylcholine esterase (AChE) activity. Treatment with nicorandil, clinidipine and GSPE was shown to significantly improve memory performance, attenuate oxidative damage and enhance AChE activity in rats. The present study also suggests that a combination of nicorandil, clinidipine, and GSPE has a better neuroprotective effect against subacute CPF induced neurotoxicity than if applied individually. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1017-1026, 2016.

The Association between Pesticide Exposure and the Development of Fronto-Temporal Dementia-Cum-Dissociative Disorders: A Review

“…It has been reported that chronic administration of chlorpyrifos significantly impaired learning, memory, and motor coordination [ 63 ]. Exposure to pesticides such as parathion, hexachlorocyclohexane, and aldrin resulted in an increased risk of dementia and the subsequent onset of Alzheimer’s disease [ 64 ].…”

Protective effect of total saponins of ginseng stems and leaves (GSLS) on chlorpyrifos-induced brain toxicity in mice through the PTEN/PI3K/AKT axis

“…Inhibition of AChE leads to the accumulation of acetylcholine in the synapses, which leads to continuous overstimulation of the nervous system, thus probably leading to the death of the organism [ 42 ]. Different doses of CPF have been reported to inhibit acetylcholinesterase, causing acetylcholine accumulation in synaptosomes, thereby inducing learning and memory dysfunction [ 43 , 44 ]. Evidently, CPF can inhibit acetylcholinesterase activity through promoting serine site phosphorylation [ 45 ].…”

Investigating the protective effect of aerobic exercise on oxidative stress and histological damages of testicular tissue associated with chlorpyrifos in male rats

“…Testis damage was induced in the exposure groups by intraperitoneal injection of CPF in DMSO at doses of 1.0 and 3.0 mg/kg body weight (b. wt) (Slotkin, Levin, & Seidler, ). Injections were performed 5 days a week (single daily injection) for 2, 4 or 6 consecutive weeks (Singh et al, ; Singh & Panwar, ; Wang et al, ). Rats in the vehicle‐treated control group (sham groups) were administered to the equal volume of vehicle (DMSO in 0.9% saline).…”