Adjuvant potential of selegiline in treating acute toxicity of aluminium phosphide in rats

• Published in: Basic & clinical pharmacology & toxicology Vol. 125; no. 1; pp. 62 - 74
• Main Authors: Maleki, Adeleh, Hosseini, Mir‐Jamal, Rahimi, Nastaran, Abdollahi, Alireza, Akbarfakhrabadi, Amir, Javadian, Nina, Amiri, Shayan, Behnoush, Behnam, Dehpour, Ahmad Reza
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.07.2019
• Subjects: Acute toxicity; aluminium phosphide; Aluminum; Aluminum Compounds - poisoning; Amine oxidase (flavin-containing); Animal tissues; Animals; Antidotes; Antidotes - administration & dosage; Antioxidants; Apoptosis; cardiac toxicity; Collapse; Disease Models, Animal; Drug Evaluation, Preclinical; Duodenum; Duodenum - drug effects; Duodenum - pathology; Echocardiography; EKG; Glutathione; Heart - drug effects; Heart rate; Humans; Injections, Intraperitoneal; Injuries; Intoxication; Male; Malondialdehyde; Medical treatment; Membrane potential; Membrane Potential, Mitochondrial - drug effects; Mitochondria; Mitochondria - drug effects; Mitochondria - pathology; Mood; Mortality; Movement disorders; Myocardium - pathology; Neurodegenerative diseases; Neurotoxicity; Oxidative stress; Oxidative Stress - drug effects; Parameters; Parkinson's disease; Pesticides - poisoning; Phosphides; Phosphine; Phosphines - poisoning; Poisoning; Poisoning - drug therapy; Poisoning - etiology; Poisoning - pathology; rat; Rats; Reactive oxygen species; Reactive Oxygen Species - metabolism; Selegiline; Selegiline - administration & dosage; Stomach; Stomach - drug effects; Stomach - pathology; Toxicity; Treatment Outcome; aluminium phosphide; cardiac toxicity; rat; mitochondria; selegiline
• ISSN: 1742-7835; 1742-7843; 1742-7843
• DOI: 10.1111/bcpt.13207

Aluminium phosphide (AlP) is a highly toxic substance with a high mortality rate and no effective antidote. Once exposed to the moisture and acidic conditions of the stomach, AlP releases toxic phosphine (PH3) gas, which results in severe toxicity in poisoned subjects. Selegiline is a monoamine oxidase inhibitor with antioxidant and anti‐apoptotic properties, which is mostly prescribed for the treatment of mood disorders and Parkinson's disease. Since AlP has detrimental effects on cardiac physiology and mitochondrial function, we tested the protective effects of acute selegiline treatment on cardiac mitochondrial function, redox status and electrocardiographic parameters in rats after AlP poisoning. To do this, AlP was given to rats by gavage to induce toxicity. Selegiline was injected intraperitoneally in the treatment groups 1 hour after AlP poisoning. Selegiline treatment after AlP intoxication was not associated with a significant difference in the mortality rate of animals. However, selegiline reduced oxidative stress (decreased the reactive oxygen species and malondialdehyde) and increased glutathione in the cardiac tissue of rats exposed to AlP. Further, the mitochondrial membrane potential (ΔΨm) collapse reversed after treatment with selegiline. Selegiline also improved the electrocardiographic (ECG) parameters and enhanced heart rate. The histopathological evaluation revealed that selegiline eliminated the inflammation and injuries induced by AlP in the stomach and duodenum, as well as cardiac tissue. In conclusion, selegiline treatment can ameliorate the AlP‐induced cardiac and gastrointestinal injuries in rats via boosting redox status and mitochondrial function with no significant effect on survival. We suggest that using selegiline, apart from other clinical treatments, may improve the quality of treatment process for AlP toxicity.