Aminoguanidine improves survival and attenuates hypotension and oxidative stress in aluminum phosphide-poisoned rats

This study aimed to evaluate the therapeutic efficacy of aminoguanidine (AG), a nitric oxide synthase (NOS) inhibitor, against the fatal hypotension and systemic toxicity induced by aluminum phosphide (AlP) poisoning in a rat model. Twenty-four rats were randomly assigned to four groups (n = 6 each): (1) Control (corn oil, gavage), (2) AG alone (100 mg/kg, i.p., multiple doses), (3) AlP (15 mg/kg, gavage), and (4) AlP + AG. Following AlP exposure, multiple doses of AG were administered. We continuously monitored survival, blood pressure (BP), heart rate (HR), and electrocardiogram (ECG). Plasma nitric oxide, oxidative stress biomarkers (MDA, FRAP), and cardiac histopathology were also assessed. AlP poisoning caused 100% mortality, profound hypotension, QTc prolongation, elevated plasma NO, and extensive myocardial injury. Multiple-dose AG treatment increased survival to 50%, restored blood pressure and ECG parameters, and significantly reduced plasma NO and oxidative stress markers, which was confirmed by markedly improved cardiac histopathology. This study provides strong preclinical evidence that AG is a highly effective treatment for acute AlP poisoning by attenuating NO-associated hypotension and oxidative stress. Given the lack of a specific antidote and high global mortality, AG may therefore warrant further investigation as a potential therapeutic strategy for acute AlP poisoning.