Protection of rats against the effects of alpha-naphthylthiourea (ANTU) by elevation of non-protein sulphydryl levels.
We have investigated the influence of the elevation of pulmonary glutathione (GSH) levels on the toxicity of the rodenticide alpha-naphthylthiourea (ANTU) to rat lung. Administration of phorone (diisopropylidene acetone; 200 mg/kg i.p.) caused an initial depletion of both pulmonary and hepatic GSH followed after 48 hr by a marked elevation in both tissues, due most probably to a compensatory rebound synthesis. In control rats, ANTU produced a dose-dependent lethality, hydrothorax and loss of ability of lung tissue to accumulate adenosine and spermidine (markers of endothelial and epithelial cell function, respectively). These effects were prevented or markedly ameliorated when ANTU was given 48 hr after pretreatment with phorone. The mechanism of the protection by phorone pretreatment against ANTU-induced pulmonary toxicity is unclear. It may be due, in part, to elevated GSH levels in pulmonary endothelial cells and, in addition, to increased detoxification of ANTU in the liver, resulting in a decreased availability to the lung.
Hardwick
S J
SJ
Toxicology Unit, School of Pharmacy, University of London, U.K.
Skamarauskas
J T
JT
Smith
L L
LL
Upshall
D G
DG
Cohen
G M
GM
D000241:Adenosine / Q000378:metabolism; D000818:Animals; D005978:Glutathione / Q000378:metabolism*; D007659:Ketones / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010269:Paraquat / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D013095:Spermidine / Q000378:metabolism; D013890:Thiourea / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000633:toxicity
D007659:Ketones; C018637:phorone; D005978:Glutathione; D013890:Thiourea; D000241:Adenosine; D010269:Paraquat; D013095:Spermidine; C005277:alpha-naphthyl thiourea