Influence of Different Atropine Therapy Strategies on Fenthion‐Induced Organ Dysfunction in Rats

Abstract

Abstract:We studied the influence of dose and timing of atropine therapy on fenthion-induced organ dysfunction. Thirtysix rats were randomized into six groups. All rats in the five groups except the control group were intoxicated with fenthion. The high-dose atropine group received 2 mg/kg of atropine, whereas the low-dose group received 100 µ g/kg of atropine every hour for 24 hr. One group received 2 mg/kg of atropine in the first 4 hr of intoxication while the other group received 2 mg/kg of atropine in the last 4 hr before killed, which for all rats was 24 hr after intoxication. Pseudocholinesterase and aspartate aminotransferase and alanine aminotransferase levels and histopathological markers of lung, brain and liver were studied. None of our atropine therapy strategies in this study totally prevented harm on the three organs. Although the high dose of atropine administered for 24 hr had the least harmful markers for lung, it also had the most harmful markers for brain and liver. We did not succeed in finding a unique therapy strategy in our models beneficial for all studied organs in fenthion intoxication in rats. Atropine administration strategy should be oriented for the most affected organ pathology in fenthion intoxication.Organophosphate drugs are used as pesticides in agriculture. Physicians mainly treat patients with organophosphate intoxication because of accidental exposure to high doses of the drug or suicide attempt. Because of their high toxicity, organophosphates cause severe morbidity and mortality [1]. The widespread use of organophosphates has long been known to exert deleterious effects on living organisms [2].Acute organophosphate intoxication causes postsynaptic acetylcholine accumulation that results in stimulation of the autonomic nervous system, central nervous system and the skeletal muscle [3]. Additionally, dimethoate as an organophosphate drug induces hepatocellular damage and ischaemic changes of the brain [4].Although alternative agents to reduce organophosphateinduced mortality are being searched for [5], atropine remains one of the major drugs to be used in organophosphate intoxication. Atropine is the competitive antagonist of acetylcholine at the muscarinic postsynaptic membrane and is administered to obtain the required clinical response in the treatment of organophosphate intoxication. Atropine is administered until dry skin and bronchial secretions are obtained and prevention of myosis and bradycardia is usually not sufficient [6]. However, this therapeutic goal is needed for every patient, although every patient has a different degree of intoxication and it is difficult to estimate clinical responses of each patient. For these reasons, different doses of atropine are administered to every patient at different times of intoxication.Accumulation of excessive acetylcholine at muscarinic and nicotinic receptors is accused to cause toxic effects and organ dysfunctions (e.g. in lungs) [1,3] due to fenthion. Additionally, atropine that is the competitive antagonist of acetylch...

Technetium-99mdiethylenetriaminepentaacetic acid radioaerosol scintigraphy in organophosphate induced pulmonary toxicity: Experimental study

“…If lung changes were due to aspiration, lung changes would be seen only in rabbits that aspirated fenthion and the lung changes seen in group 2 wouldn't be uniform among rabbits. In addition, studies have shown that subcutaneous administration of fenthion causes lung injury (19,32). For these reasons, we believe that the changes were due to systemic absorption of fenthion.…”