Mechanisms of muscular electrophysiological and mitochondrial dysfunction following exposure to malathion, an organophosphorus pesticide

Human and Experimental Toxicology - Tập 33 Số 3 - Trang 251-263 - 2014
Somayyeh Karami‐Mohajeri1,2, Mohammad Reza Hadian3, Shamileh Fouladdel1, Ebrahim Azizi1, M H Ghahramani1, Reshad Hosseini1, Mohammad Abdollahi1
1Department of Toxicology and Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences (TUMS), Tehran, Islamic Republic of Iran
2Department of Toxicology and Pharmacology, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Islamic Republic of Iran
3Electrophysiology Laboratory, Faculty of Rehabilitation, Tehran University of Medical Sciences (TUMS), Tehran, Islamic Republic of Iran

Tóm tắt

Muscle dysfunction in acute organophosphorus (OP) poisoning is a cause of death in human. The present study was conducted to identify the mechanism of action of OP in terms of muscle mitochondrial dysfunction. Electromyography (EMG) was conducted on rats exposed to the acute oral dose of malathion (400 mg/kg) that could inhibit acetylcholinesterase activity up to 70%. The function of mitochondrial respiratory chain and the rate of production of reactive oxygen species (ROS) from intact mitochondria were measured. The bioenergetic pathways were studied by measurement of adenosine triphosphate (ATP), lactate, and glycogen. To identify mitochondrial-dependent apoptotic pathways, the messenger RNA (mRNA) expression of bax and bcl-2, protein expression of caspase-9, mitochondrial cytochrome c release, and DNA damage were measured. The EMG confirmed muscle weakness. The reduction in activity of mitochondrial complexes and muscular glycogen with an elevation of lactate was in association with impairment of cellular respiration. The reduction in mitochondrial proapoptotic stimuli is indicative of autophagic process inducing cytoprotective effects in the early stage of stress. Downregulation of apoptotic signaling may be due to reduction in ATP and ROS, and genotoxic potential of malathion. The maintenance of mitochondrial integrity by means of artificial electron donors and increasing exogenous ATP might prevent toxicity of OPs.

Từ khóa


Tài liệu tham khảo

Wilson JD, Llados FT, Singh M, Sutton CA, Sutton WR, Nakatsugawa T, Toxicological profile for malathion. Atlanta, GA: Agency for Toxic Substances and Disease Registry, 2003, pp.17–18.

10.1002/9780470640500

10.1016/j.taap.2013.01.025

Balali-Mood M, 2012, Iran J Public Health, 41, 1

10.1080/00039896.1970.10667285

Farago A, 1967, Arch Toxicol, 23, 11

10.1080/00039896.1978.10667342

10.1289/ehp.01109471

10.1002/9780470640500.ch30

10.2165/00139709-200625010-00001

10.1177/0960327106080453

10.1191/0960327106ht602oa

10.1016/j.taap.2011.11.014

Cavaliere MJ, 1998, Clin Toxicol (Phila), 36, 295

10.1016/S0161-813X(02)00111-0

10.1016/0005-2728(94)90099-X

10.2337/db11-0121

10.1155/2012/329635

10.1080/15376510802455354

10.1002/mus.10194

10.1177/0960327110388959

Kacew S, 1996, J Toxicol Env Heal A, 47, 1

10.1016/S0015-6264(65)80206-1

Abdollahi M, 1998, Acta Med Iranica, 36, 74

10.1016/0014-4886(86)90315-8

10.1042/BJ20060766

William SA, Immo ES. Methods in enzymology. Mitochondrial function, part A: mitochondrial electron transport complexes and reactive oxygen species. 1st ed. London, UK: Elsevier Inc. 2009, pp. 174–179.

Pon LA, 2001, Methods in cell biology, 104

10.1016/S0021-9258(18)44883-1

10.1002/ajmg.a.31194

Hosseini A, 2010, Int J Nanomedicine, 5, 517

10.1152/jappl.1970.28.2.234

10.1016/0009-8981(68)90258-1

10.1016/j.abb.2004.07.025

10.1097/00024382-199905000-00006

10.1136/jnnp.50.11.1442

10.1016/S0022-510X(98)00058-6

10.2165/00139709-200524010-00003

Singh G, 1998, Neurol India, 46, 28

Wecker L, 1978, Fed Proc, 37, 2818

10.1016/0272-0590(84)90134-9

De Bleecker J, 1991, Acta Neurol Belg, 91, 255

10.1016/j.pestbp.2006.10.003

10.1177/0748233711412423

10.1016/j.neuropharm.2006.06.024

10.1007/BF00999384

10.1016/S0300-483X(02)00038-0

10.1038/249662a0

10.1016/j.tcb.2012.05.001

10.1016/j.mito.2011.02.001

10.1016/j.etap.2006.09.003

Soltaninejad K, 2009, Med Sci Monit, 15, 75

10.2337/db10-0818

10.1016/S0278-6915(00)00019-3

Abdollahi M, 2004, Med Sci Monit, 10, 141

10.1007/s11064-006-9111-1

10.1016/S0891-5849(00)00417-2

10.2337/diabetes.51.10.2944

10.1006/abbi.2001.2486

10.1006/scdb.2001.0282

10.1128/JVI.72.11.8586-8596.1998

10.1038/emboj.2009.369

10.1016/j.cbi.2010.03.034

10.1016/j.tins.2006.02.005

10.1158/0008-5472.CAN-04-0649

10.1038/sj.cdd.4401034

10.1023/A:1018413522959

10.1016/S1383-5718(99)00132-1

10.1152/physrev.00015.2008

10.1196/annals.1254.007

10.1002/(SICI)1097-4598(200004)23:4<453::AID-MUS3>3.0.CO;2-O

10.1186/1478-811X-7-20

10.1016/j.bbamcr.2011.11.001

Preussmann R, 1969, Arzneimittelforschung, 19, 1059

10.1007/s00244-009-9354-3

10.1191/0960327105ht549oa

10.1074/jbc.M011643200

10.3923/ijp.2012.708.710

10.3923/ijp.2012.473.474

10.3923/ijp.2012.467.469

10.3923/ijp.2012.139.140

10.3109/15376516.2010.518173

Thông tin
Thông tin xuất bản

Human and Experimental Toxicology

Tập 33 Số 3

251-263

Thông tin tác giả