Protective effect of an adenosine A1 receptor agonist against metamidophos-induced toxicity and brain oxidative stress.
The aim of this study was to evaluate the effects of different doses of an adenosine A(1) selective agonist, phenylisopropyl adenosine (PIA), on metamidophos-induced cholinergic symptoms, mortality, diaphragm muscle necrosis, and brain oxidative stress. A LD(50) 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.
Department of Pharmacology, Dokuz Eylul University, School of Medicine, Balcova Izmir, Turkey. sule.kalkan@deu.edu.tr
Sule
S
Kalkan
Durgul
D
Ozdemir
Bekir Ugur
BU
Ergur
Nazan Uysal
NU
Hazardin
Aylin
A
Akgun
Ayca
A
Topcu
Yusuf Cem
YC
Kaplan
Nil
N
Hocaoglu
Kubilay
K
Oransay
Yesim
Y
Tuncok
D000241:Adenosine / Q000031:analogs & derivatives*; D058907:Adenosine A1 Receptor Agonists; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003964:Diaphragm / Q000187:drug effects / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007306:Insecticides / Q000633:toxicity*; D007928:Lethal Dose 50; D008297:Male; D009946:Organothiophosphorus Compounds / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D015996:Survival Rate; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D058907:Adenosine A1 Receptor Agonists; D000975:Antioxidants; D007306:Insecticides; D009946:Organothiophosphorus Compounds; D017392:Thiobarbituric Acid Reactive Substances; C014655:methamidophos; D000241:Adenosine