Volume 17, Issue 39, January - June, 2023

Effect of propranolol, bisoprolol and terbutaline in acute brain injury induced by malathion in the rat

Omar ME Abdel-Salam^1♦, Fatma A Morsy², Amany A Sleem³

¹Department of Toxicology and Narcotics, Medical Research and Clinical Studies Institute, National Research Centre, Cairo, Egypt
²Department of Pathology, Medical Research and Clinical Studies Institute, National Research Centre, Cairo, Egypt
³Department of Pharmacology, Medical Research and Clinical Studies Institute, National Research Centre, Cairo, Egypt

^♦Corresponding author
Department of Toxicology and Narcotics, Medical Research and Clinical Studies Institute, National Research Centre, Dokki, Cairo Egypt

ABSTRACT

The pharmacological management of acute malathion poisoning entails besides the use of the specific antidotes atropine and oximes, the administration of other drugs for controlling associated cardiac and respiratory problems. In this study, we aimed to investigate the effect of the non-selective β-adrenoceptor blocker propranolol, the selective β1-adrenoceptor antagonist bisoprolol as well as the bronchodilator drug and the selective β2-adrenoceptor agonist terbutaline, either alone or in combination with atropine on brain oxidative stress and neuronal damage caused by acute malathion administration. Rats were treated with malathion at 150 mg/kg by intraperitoneal (i.p.) injection for two days either alone or combined with propranolol, bisoprolol or turbutaline all at the dose of 1 mg/kg, i.p. Brain damage was assessed by measuring the levels of the oxidative stress biomarkers malondialdehyde, reduced glutathione and nitric oxide in brain tissue and by brain histopathology. Results indicated significant increase in the brain lipid peroxidation marker malondialdehyde and nitric oxide as well as depletion of reduced glutathione in brain of malathion only- treated rats. In the cerebral cortex, focal homogenous deeply eosinophilic plaques, gliosis, neuronal apoptosis, necrosis, perineuronal vacuolation and spongiform degeneration were observed after exposure to malathion. The biochemical changes of malathion were decreased by atropine and β-blockers in addition to marked amelioration of the malathion-induced histopthaological effects. The administration of terbutaline to malathion-treated rats had no significant effects on brain oxidative stress. The extent of histological brain damage (neurodegeneration) was not reduced after terbutaline. The administration of atropine was able to ameliorate the neuropathological changes in brain of rats treated with malathion and β- adrenergic antagonists but not in case of terbutaline. Collectively, the present results indicate that β-blockade may decrease the neurodegeneration in brain of malathion-treated rats. The results also suggest a role for β-adrenoceptor stimulation in the development of the cerebral damage by malathion.

Keywords: Beta adrenoceptors, propranolol, bisoprolol, terbutaline, neuronal injury, malathion toxicity

Drug Discovery, 2023, 17(39), e9dd1010

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DOI: https://doi.org/10.54905/disssi.v17i39.e9dd1010

Published: 14 February 2023