Protective Effect of an Adenosine A₁ Receptor Agonist Against Metamidophos-Induced Toxicity and Brain Oxidative Stress

Abstract

The aim of this study was to evaluate the effects of different doses of an adenosine A₁ selective agonist, phenylisopropyl adenosine (PIA), on metamidophos-induced cholinergic symptoms, mortality, diaphragm muscle necrosis, and brain oxidative stress. A LD₅₀ dose of metamidophos (20 mg/kg body weight, p.o.) was followed by 1 mL/kg body weight of 0.9% NaCl or 1 mg/kg, 2 mg/kg, 3 mg/kg, or 5 mg/kg body weight PIA ip. Incidence of clinical signs including chewing, salivation, convulsion, and respiratory distress did not show any significant difference among all treatment groups (p > 0.05). PIA was found to be effective to reverse the necrotic changes in diaphragm muscle induced by metamidophos significantly in all groups. Brain Thiobarbituric Acid Reactive Substance (TBARS) levels were significantly increased after the metamidophos poisoning. Administration of 2 to 5 mg/kg body weight PIA decreased brain TBARS levels compared to 0.9% NaCl treated rats. The results indicate that, although different doses of PIA reduced the OP-induced oxidative stress and diaphragm necrosis, a single dose of PIA was not able to recover cholinergic signs and symptoms of metamidophos poisoning.

KEYWORDS:

• Organophosphate (OP)
• Oxidative Stress
• Phenylisopropyl Adenosine (PIA)

This study was supported partly by Dokuz Eylul University Research Foundation with the grant number 04.KB.SAG.068. This study was prresented as a poster presentation in North American Congress of Clinical Toxicology Annual Meeting, New Orleans, Louisiana, 2007. Additionally, it was presented as a poster at Turkish Pharmacology Society, 19th National Congress of Pharmacology, 2nd Clinical Toxicology Symposium, 3rd Clinical Pharmacology Symposium, Trabzon, Turkey, 2007.