Investigations on organophosphorus insecticideinduced neurotoxicity with Caenorhabditis elegans as a model system

Kisan, B. (2009) Investigations on organophosphorus insecticideinduced neurotoxicity with Caenorhabditis elegans as a model system. PhD thesis, University of Mysore.

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Abstract

The main objectives of the thesis were to (a) develop a model system employing Caenorhabditis elegans for investigating the toxicity of selected organophosphorus insecticides (OPI) using multiple end-points (b) investigate the biochemical mechanisms involved in OPI toxicity in C. elegans (c) compare the pattern and extent of cholinesterase inhibition induced by OPI in C. elegans and rat brain homogenates in vitro. Our experimental approach involved behavioral, physiological and biochemical studies employing C. elegans as a model system. Initially we screened three OPI dichlorvos (DDVP), dimethoate (DM) and monocrotophos (MC) for their toxicity in N2 and (PC 72) strain of C. elegans. Results revealed that DDVP was most toxic and all the three OPI elicited Hsp response in the transgenic strain. A good correlation was evident between feeding inhibition, AChE inhibition and Hsp induction in dichlorvos treated worms. Dichlorvos at sublethal concentrations induced cessation in feeding and paralysis in C. elegans (N2) and these worms also hyper contracted their nose muscles and showed marked decrease in egg laying. The treated worms exhibited significant reduction in the AChE activity and increase in ACh content. Worms exposed to both dichlorvos + atropine showed inhibition in feeding as in worms treated with dichlorvos alone. Worms exposed to dichlorvos + atropine showed a concentration related decrease in the extent of paralysis while worms treated with dichlorvos + atropine followed by treatment with 2-PAM showed 100% recovery from AChE and feeding inhibition. Exposure to dichlorvos significantly decreased the brood size, decreased life span, increased reactive oxygen species and altered antioxidant status in the worms. The results of the qualitative analysis of the fatty acid methyl esters derived from lipids of the worms exposed to dichlorvos showed variations in the fatty acids. Exposure to dichlorvos resulted in significant accumulation of lipofuscin throughout body of the worm. Comparative kinetic studies with AChE of rat brain homogenate and C. elegans homogenate revealed inhibition of AChE to be of irreversible in nature in both the systems. AChE of C. elegans was more sensitive to inhibition by dichlorvos. A similar pattern of inhibition was also observed with carboxylesterase of C. elegans. In conclusion, data obtained from the present series of investigations support the premise that the nematode, C. elegans is a good model organism for studying the neurotoxicity of OPI, since this organism offers several simple and easily measurable physiological and biochemical endpoints for studying the mechanistic toxicity of the OPI.

Item Type:	Thesis (PhD)
Uncontrolled Keywords:	Caenorhabditis elegans; toxicity; organophosphorus insecticides (OPI); Biochemical mechanism; Impact of low doses of dichlorvos
Subjects:	600 Technology > 01 Medical sciences > 17 Toxicology 500 Natural Sciences and Mathematics > 04 Chemistry and Allied Sciences > 26 Pesticide Chemistry
Divisions:	Food Protectants and Infestation Control
Depositing User:	Food Sci. & Technol. Information Services
Date Deposited:	12 Mar 2010 10:37
Last Modified:	12 Mar 2010 10:37
URI:	http://ir.cftri.res.in/id/eprint/9384

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