Effect of preinduction of metallothionein on paraquat toxicity in mice.
The effect of pretreatment with metallothionein (MT)-inducing metals (Zn, Cu, Bi, Co, Cd or Hg) on paraquat (PQ) toxicity was investigated in mice. PQ lethality was remarkably reduced by pretreatment with the above MT-inducing metals. The protective effect of pretreatment with these metals on PQ lethality was significantly correlated with MT levels in the lung, a target tissue of PQ toxicity, in mice administered MT-inducing metals, but not with MT in the liver or kidney. The increase in pulmonary lipid peroxidation in mice treated with PQ was significantly inhibited by Zn pretreatment. Zn was the most effective of the MT-inducing metals used in this experiment in protecting mice against PQ lethality. Of those monitored, the only pulmonary free radical scavenging factor increased by Zn pretreatment was MT. Other free radical scavenging factors (activities of superoxide dismutase, glutathione peroxidase and catalase, and concentration of non-protein thiols level) were not influenced by Zn treatment. These results indicate that the induction of pulmonary MT protects against the lethality and lung toxicity of PQ. Pulmonary MT may scavenge free radicals produced by PQ, thereby protecting against lethal pulmonary toxicity.
Satoh
M
M
Department of Public Health, School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
Naganuma
A
A
Imura
N
N
D000818:Animals; D004790:Enzyme Induction / Q000187:drug effects; D016166:Free Radical Scavengers; D015227:Lipid Peroxidation / Q000187:drug effects; D008168:Lung / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008668:Metallothionein / Q000096:biosynthesis*; D008670:Metals / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D010269:Paraquat / Q000037:antagonists & inhibitors / Q000633:toxicity*
D016166:Free Radical Scavengers; D008670:Metals; D008668:Metallothionein; D010269:Paraquat