Investigation of in vitro effects of ethephon and chlorpyrifos, either alone or in combination, on rat intestinal muscle contraction

Çetinkaya, Mustafa; Baydan, Emine

doi:10.2478/v10102-010-0002-6

Abstract

A range of pesticides is widely used in pest management and the chances of exposure to multiple organophosphorus (OP) compounds simultaneously are high, especially from dietary and other sources. Although health hazards of individual OP insecticides have been relatively well characterized, there is lesser information on the interactive toxicity of multiple OP insecticides. The aim of this study is to elicit the possible interactions in case combined exposure of an OP pesticide chlorpyrifos (CPF) and a plant growth regulator ethephon (ETF) which are used worldwide. The ileum segments of 3 months old Wistar Albino male rats were used in isolated organ bath containing Tyrode solution. ETF and CPF were incubated (10^-7 M concentration) separately or in combination with each other to ileum and their effects on acetylcholine-induced contractions were studied. The data obtained from this study show that, single and combined exposure to the agents caused agonistic interactions with regard to potency of ACh whereas they caused a decrease on E_max value of ACh. These findings suggest that exposure to these agents which have direct and indirect cholinergic effects, may cause developing clinical responses with small doses and earlier but the extent of toxicity will be lower.

References

Axelrad JC, Howard CV and McLean WG. (2002). Interactions between pesticides and components of pesticide formulations in an in vitro neurotoxicity test. Toxicology 173: 259-268.
Search in Google Scholar
Becerra MA, Herrera MD and Marhuenda E. (2001). Action of tacrine on muscarinic receptors in rat intestinal smooth muscle. J Auton Pharmacol 21: 113-119.
Search in Google Scholar
Chanda SM, Mortensen SR, Moser VC, Padilla S. (1997). Tissue-Spesific Effects of Chlorpyrifos on Carboxylesterase and Cholinesterase Activity in Adult Rats: An in Vitro and in Vivo Comparison. Fundam App Toxicol 38: 148-157.
Search in Google Scholar
Cochran RC. (2002). Appraisal of Risks from Nonoccupational Exposure to Chlorpyrifos. Reg Toxicol Pharmacol 35: 105-121.
Search in Google Scholar
Cook TJ and Shenoy SS. (2003). Intestinal permeability of chlorpyrifos using the single-pass intestinal perfusion method in the rat. Toxicology 184: 125-133.
Search in Google Scholar
El-Masri HA, Mumtaz MM and Yushak ML. (2004). Application of physiologically-based pharmacokinetic modeling to investigate the toxicological interaction between chlorpyrifos and parathion in the rat. Environ Tox Pharm 16: 57-71.10.1016/j.etap.2003.10.002
Search in Google Scholar
EPA. (1995). Reregistration Eligibility Decision (RED): Ethephon. List A Case 0382. U.S. Environmental Protection Agency. Office of Prevention, Pesticides and Toxic Substances. Washington, D.C. 20460. Available from: http://www.epa.gov/REDs/0382.pdf
Search in Google Scholar
Haux JE, Lockridge O and Casida JE. (2002). Specificity of Ethephon as a Butyrylcholinesterase Inhibitor and Phosphorylating Agent. Chem Res Toxicol 15: 1527-1533.10.1021/tx020042w
Search in Google Scholar
Haux JE, Quistad GB and Casida JE. (2000). Phosphobutyrylcholinesterase: Phosphorylation of the Esteratic Site of Butyrylcholinesterase by Ethephon [(2-Chloroethyl)phosphonic Acid] Dianion. Chem Res Toxicol 13: 646-651.10.1021/tx000027w
Search in Google Scholar
Howard MD and Pope CN. (2002). In vitro effects of chlorpyrifos, parathion, methyl parathion and their oxons on cardiac muscarinic receptor binding in neonatal and adult rats. Toxicology 170: 1-10.10.1016/S0300-483X(01)00498-X
Search in Google Scholar
Karanth S, Liu J, Olivier KJr, Pope C. (2004). Interactive toxicity of the organophosphorus insecticides chlorpyrifos and methyl parathion in adult rats. Toxicol Appl Pharmacol 196: 183-190.10.1016/j.taap.2003.12.014
Search in Google Scholar
Kousba AA, Poet TS and Timchalk C. (2003). Characterization of the in vitro kinetic interaction of chlorpyrifos-oxon with rat salivary cholinesterase: A potential biomonitoring matrix. Toxicology 188: 219-232.10.1016/S0300-483X(03)00090-8
Search in Google Scholar
Poet TS, Wu H, Kousba AA, Timchalk C. (2003). In Vitro Rat Hepatic and Intestinal Metabolism of the Organophosphate Pesticides Chlorpyrifos and Diazinon. Toxicol Sci 72: 193-200.10.1093/toxsci/kfg03512655035
Search in Google Scholar
Pope C, Karanth S and Liu J. (2005). Pharmacology and toxicology of cholinesterase inhibitors: uses and misuses of a common mechanism of action. Environ Tox Pharm 19: 433-446.10.1016/j.etap.2004.12.04821783509
Search in Google Scholar
Segall Y, Grendell RL, Toia RF, Casida JE. (1991). Composition of Technical Ethephon [(2-Chloroethyl)phosphonic Acid] and Some Analogues Relative to Their Reactivity and Biological Activity. J Agric Food Chem 39: 380-385.10.1021/jf00002a031
Search in Google Scholar
Smegal DC. (2000). Human Health Risk Assessment: Chlorpyrifos. U.S. Environmental Protection Agency. Office of Pesticide Programs, Health Effects Division (7509C). Available from: http://www.epa.gov/pesticides/op/chlorpyrifos/hedrra.pdf
Search in Google Scholar
Sparks SE, Quistad GB and Casida JE. (1999). Organophosphorus Pesticide-Induced Butyrylcholinesterase Inhibition and Potentiation of Succinylcholine Toxicity in Mice. J Biochem Molecular Tox 13: 113-118.10.1002/(SICI)1099-0461(1999)13:2<;113::AID-JBT7>3.0.CO;2-8
Search in Google Scholar
Taha MO, Fraga MM, Fagundes DJ, Bandeira CP, Caricati-Neto A, Jurkiewicz A. (2002). Effect of Preservation Conditions on Autonomic Transmission in Rat Small Bowel. Transplantation Proceedings 34: 1021-1024.10.1016/S0041-1345(02)02698-2
Search in Google Scholar
Tezuka A, Ishihata A, Aita T, Katano Y. (2004). Aging-related alterations in the contractile responses to acetylcholine, muscarinic cholinoceptors and cholinesterase activities in jejunum and colon of the male Fischer 344 rats. Experimental Gerontology 39: 91-100.
Search in Google Scholar
Timchalk C, Nolan RJ, Mendrala AL, Dittenber DA, Brzak KA, Mattsson JL. (2002). A physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model for the organophosphate insecticide chlorpyrifos in rats and humans. Toxicol Sci 66: 34-53.
Search in Google Scholar
Timchalk C, Poet TS, Hinman MN, Busby AL, Kousba AA. (2005). Pharmacokinetic and pharmacodynamic interaction for a binary mixture of chlorpyrifos and diazinon in the rat. Toxicol Appl Pharmacol 205: 31-42.
Search in Google Scholar
Tomlin CDS. (1997). The Pesticide Manual: A World Compendium. 11th Ed. The British Crop Protection Council.
Search in Google Scholar
Zhang N and Casida JE. (2002). Novel Irreversible Butyrylcholinesterase Inhibitors: 2-Chloro-1-(substituted-phenyl)ethylphosphonic Acids. Bioorg Med Chem 10: 1281-1290.
Search in Google Scholar

Investigation of in vitro effects of ethephon and chlorpyrifos, either alone or in combination, on rat intestinal muscle contraction

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