Cromakalim, a Potassium Channel Opener, Ameliorates the Organophosphate and Carbamate-Induced Seizure in Mice
Organophosphates (OPs) and carbamates are acetylcholine esterase inhibitors (AChEIs), which can cause seizure and lethality. Anticonvulsant properties of potassium channel openers including cromakalim have been determined in previous studies. In the present experiment, the possible effect of cromakalim on the convulsion and death induced by OPs and carbamates was studied in mice. Dichlorvos (an OP, 50 mg/kg) and physostigmine (a carbamate, 2 mg/kg) were used to induce seizure in animals. Cromakalim at doses of 0.1, 10, and 30 µg/kg was injected 30 min before dichlorvos and physostigmine, and 5 min before glibenclamide (a potassium channel blocker, 1 mg/kg) administration. All injections were performed intraperitoneally. After drugs administration, the onset of convulsion, death, the severity of seizure, and rate of mortality were investigated. Results revealed that both dichlorvos and physostigmine induced seizure activity and lethality in 100% of the animals. Cromakalim at doses of 0.1, 10, and 30 µg/kg significantly increased the latency of both seizure and death (P<0.05). Also, cromakalim decreased the mortality rate induced by dichlorvos and physostigmine (P<0.05). On the other hand, glibenclamide blocked all aspects of the anticonvulsant effect of cromakalim (P<0.05). This study revealed for the first time that cromakalim (a KATP channel opener) diminishes the seizure and death induced by dichlorvos and physostigmine in mice, and introduces a new aspect to manage the patients who suffer from OPs/carbamates-induced seizure.
Cocker J, Mason H, Garfitt S, et al.Biological monitoring of exposure to organophosphate pesticides. Toxicology letters 2002; 134 (1) : 97-103.
Millard CB, Broomfield CA.Anticholinesterases: medical applications of neurochemical principles.Journal of neurochemistry 1995; 64( 5): 1909-1918.
Fukuto TR. Mechanism of action of organophosphorus and carbamate insecticides.Environmental Health Perspectives1990; 87:245-254
Cable GG, Doherty S. Acute carbamate and organochlorine toxicity causing convulsions in an agricultural pilot: a case report. Aviation, space, and environmental medicine1999; 70(1):68-72.
Jazayeri A, Zolfaghari S, Ostadhadi S.Anticonvulsant Effect of Diazoxide against Dichlorvos-Induced Seizures in Mice. The Scientific World Journal 2013;2013:1-4.
Lallement G, Dorandeu F, Filliat P, et al.Medical management of organophosphate-induced seizures. Journal of Physiology-Paris 1998 ; 92(5): 369-373.
Munro NB, Watson AP, Ambrose KR, et al.Treating exposure to chemical warfare agents: implications for health care providers and community emergency planning. Environmental Health Perspectives1990; 89: 205–215
Yamada K, Inagaki N.Neuroprotection by K< sub> ATP channels. Journal of molecular and cellular cardiology 2005; 38( 6): 945-949.
Shafaroodi H, Asadi S, Sadeghipour H, et al.Role of ATP-sensitive potassium channels in the biphasic effects of morphine on pentylenetetrazole-induced seizure threshold in mice. Epilepsy research 2007; 75(1): 63-69.
Ghasemi M, Shafaroodi H, Karimollah AR, etal. ATP-sensitive potassium channels contribute to the time-dependent alteration in the pentylenetetrazole-induced seizure threshold in diabetic mice.Seizure 2010; 19( 1):53-58.
Wickenden AD.Potassium channels as anti-epileptic drug targets. Neuropharmacology 2002; 43(7):1055-1060.
Porter RJ, Rogawski MA.New antiepileptic drugs: from serendipity to rational discovery.Epilepsia 1992; 33, (s1): S1-S6.
Narita M, Suzuki T, Misawa M, et al .Role of central ATP-sensitive potassium channels in the analgesic effect and spinal noradrenaline turnover-enhancing effect of intracerebroventricularly injected morphine in mice. Brain research 1992; 596 (1):209-214.
Yamada K, Ji JJ, Yuan H, Miki T, et al .Protective role of ATP-sensitive potassium channels in hypoxia-induced generalized seizure. Science 2001; 292(5521:1543-1546.
Singh NA, Charlier C, Stauffer D,et al. A novel potassium channel gene, KCNQ2, is mutated in an inherited epilepsy of newborns.Nature genetics 1998; 18(1) ;25-29.
Dekundy A, Kaminski RM, Turski WA.Dizocilpine improves beneficial effects of cholinergic antagonists in anticholinesterase-treated mice. Toxicological Sciences 2003:72(2); 289-295.
McLean M, Gupta R, Dettbarn W ,et al. Prophylactic and therapeutic efficacy of memantine against seizures produced by soman in the rat . Toxicology and applied pharmacology 1992 : 112(1); 95-103,.
Tattersall J.Seizure activity post organophosphate exposure. Frontiers in bioscience: a journal and virtual library 2009: 14;3688-3711.
Dekundy A, Kaminski RM, Zielinska E,et al. NMDA antagonists exert distinct effects in experimental organophosphate or carbamate poisoning in mice. Toxicology and applied pharmacology 2007: 219 (2);114-121.
Milatovic D, Gupta RC, Aschner M. Anticholinesterase toxicity and oxidative stress. The Scientific World Journal 2006: 6; 295-310,.
Sparenborg S, Brennecke L, Jaax NK ,et al. Dizocilpine (MK-801) arrests< i> status epilepticus and prevents brain damage induced by soman. Neuropharmacology 1992:31(4);357-368,.
Bowden CA, Krenzelok EP. Clinical applications of commonly used contemporary antidotes.Drug safety 1997: 16(1); 9-47.
Clement JG. Central activity of acetylcholinesterase oxime reactivators .Toxicology and applied pharmacology 1992: 112(1); 104-109.
De Weille JR, Lazdunski M.Regulation of the ATP-sensitive potassium channel," in Ion channels, 1990: 205-222, Springer.
Katsumori H, Ito Y, Higashida H,et al .Anti-and proconvulsive actions of levcromakalim, an opener of ATP-sensitive K< sup>+ channel, in the model of hippocampus-generating partial seizures in rats. European journal of pharmacology 1996:311(1);37-44.
Alzheimer C, Ten Bruggencate G. Actions of BRL 34915 (Cromakalim) upon convulsive discharges in guinea pig hippocampal slices. Naunyn-Schmiedeberg's Archives of Pharmacology 1988: 337(4) ; 429-434.
Gandolfo G, Gottesmann C, Bidard JN,et al.Subtypes of K+ channels differentiated by the effect of K+ channel openers upon K+ channel blocker-induced seizures. Brain Research 1989: 495(1); 189-192.
Ben-Ari Y, Cossart R .Kainate, a double agent that generates seizures: Two decades of progress," Trends in Neurosciences 2000: 23(11);580-587,.
Niaki SEA, Shafaroodi H, Ghasemi M, et al.Mouth breathing increases the pentylenetetrazole-induced seizure threshold in mice: A role for ATP-sensitive potassium channels.Epilepsy and Behavior 2008: 13(2);284-289.
|Issue||Vol 56, No 1 (2018)|
|Organophosphates Carbamates Potassium channel opener Seizure Mice|
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