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Modified enzyme neutralises ill-effects of toxic chemicals
PESTICIDES have acquired a dubious reputation over decades. They have been linked to several ailments and have high environmental persistence. Organophosphates are the most dangerous of them all. These chemicals inhibit neurotransmission between nerve cells by blocking an enzyme, acetyl-choline esterase (AChE), and are so deadly that some of them have been developed as nerve agents for chemical warfare.
Current therapeutic methods for treating acute poisoning by these pesticides are costly and time-taking. Russian scientists have now created a bioscavenger, a substance that can neutralise the neurotoxic effect of organophosphates, by modifying a natural human enzyme, butyryl-choline esterase (BChE), which works like AChE. It was found to effectively protect animals from the ill-effects of the toxic pesticides in the lab.
Farmers are the worst hit as uncontrolled use of organophosphates can cause hormonal imbalance, respiratory problems and cardiovascular disorders. WHO estimates that 200,000 people die every year from occupational pesticide exposure across the world and largely in developing countries like India, Pakistan and Sri Lanka.
For the study, published in PNAS on January 22, the scientists produced BChE inside E coli bacterium to obtain it in a simplified form lacking the usual complex structure of natural enzyme. They then increased its molecular size and added extra sugar residues onto its surface to form aggregates of two, three, or four BChE molecules in the blood. “This helps give the enzyme a longer life in human blood stream,” says one of the authors, G Michael Blackburn, a professor at Sheffield University in the UK.
To test the efficacy of the new bioscavenger, the scientists treated eight mice with chemically modified BChE before subjecting them to different doses of a Russian organophosphate, VR. The treated mice were able to survive over four times the standard lethal dose of VR, while mice not treated with the bioscavenger died. Moreover, after a certain period of recovery, the treated mice did not show any adverse effect of the nerve agent and behaved normally.
“The results reported are on mice models. It would have to be seen whether it can be used as a tool to prevent AChE depletion in humans,” says A K Srivastava, head of the epidemiology division at Indian Institute of Toxicology Research in Lucknow.