Effects of a selective Rho-kinase inhibitor Y-27632 on oxidative stress parameters in acute dichlorvos poisoning in rats N. Gunay 1 , B. Kose 1 , S. Demiryurek 2 , A. R. Ocak 3 , O. Erel 3 and A. T. Demiryurek 4 * 1 Department of Emergency Medicine, Faculty of Medicine, University of Gaziantep, Gaziantep, Turkey 2 Department of Physiology, Faculty of Medicine, Gazi University, Besevler, Ankara, Turkey 3 Department of Clinical Biochemistry, Faculty of Medicine, Harran University, Sanliurfa, Turkey 4 Department of Pharmacology, Faculty of Medicine, University of Gaziantep, Gaziantep, Turkey This study examined the effects of Y-27632, a selective Rho-kinase inhibitor, on organophosphate-induced acute toxicity in rats. Rats were randomly divided into four groups as control (corn oil), dichlorvos (30 mg kg 1 i.p.), 1 and 10 mg kg 1 Y-27632 þ dichlorvos groups. Cholinergic signs (fatigue, tremor, cyanosis, hyper-secretion, fasciculations) were observed in all the rats in the dichlorvos group and the mortality rate was 50%. No cholinergic findings and deaths were observed in the control and Y-27632 groups. Plasma cholinesterase activities were suppressed with dichlorvos and these reductions were attenuated with Y-27632 pretreatment. There was a marked increase in plasma malondialdehyde level in the dichlorvos group, but Y-27632 pretreatment abolished this elevation. Dichlorvos markedly depressed cardiac paraoxonase activity, but these changes were not markedly modified with Y-27632. Total antioxidant capacities, total oxidant status, oxidative stress index, total free sulfhydryl groups and catalase activities in plasma and cardiac tissues were not markedly different between the groups. No significant changes were observed with cardiac myeloperoxidase activities or plasma arylesterase and ceruloplasmin activities. In conclusion, our results suggest that Rho-kinase pathway is involved in organophosphate intoxication, and a decrease in cardiac paraoxonase activities may play a role in the pathogenesis of acute organophosphate poisoning in rats. Copyright # 2008 John Wiley & Sons, Ltd. key words —antioxidant enzymes; dichlorvos; oxidative stress; poisoning; Rho-kinase; Y-27632 INTRODUCTION Organophosphate (OP) compounds are an important cause of severe toxicity and death from acute poisoning worldwide. 1 As OP pesticides are exten- sively used in widespread applications, poisoning by these compounds represents a serious public health problem especially in developing countries. Although accidental poisoning can occur following exposure to skin or inhalation, oral intake of these agents for suicide attempts cause serious poisoning. 2,3 Among the OP pesticides, dichlorvos (dimethyl 2,2-dichlor- ovinyl phosphate, DDVP) is widely used and responsible for numerous poisonings. OP compounds act as powerful inhibitors of acetylcholinesterase, resulting in the accumulation of acetylcholine and overstimulation of cholinergic synapses in the central nervous system, somatic nerves, parasympathetic nerve endings and sweat glands. 2 Cardiac compli- cations including various arrhythmias and conduction disturbances in OP intoxication may take place after the poisoning. 3,4 Although there are many investi- gations of the cardiac toxicity of OP intoxication, its pathogenesis and underlying mechanisms are not fully known. Pesticides have been reported to induce in vitro and in vivo generation of reactive oxygen species (ROS). 5,6 cell biochemistry and function Cell Biochem Funct 2008; 26: 747–754. Published online 17 July 2008 in Wiley InterScience (www.interscience.wiley.com) DOI: 10.1002/cbf.1500 * Correspondence to: Professor A. T. Demiryurek, Department of Pharmacology, Faculty of Medicine, University of Gaziantep, Gaziantep 27310, Turkey. Tel: þ90 342 360 60 60/77740. Fax: þ90 342 360 1617. E-mail: demiryurek@gantep.edu.tr Copyright # 2008 John Wiley & Sons, Ltd. Received 7 February 2008 Revised 14 May 2008 Accepted 5 June 2008