Susceptibility of metallothionein-null mice to paraquat

• Published in: Environmental toxicology and pharmacology 1996-07, Vol.1 (4), p.221-225
• Main Authors: Sato, M., Apostolova, M.D., Hamaya, M., Yamaki, J., Choo, K.H.A., Michalska, A.E., Kodama, N., Tohyama, C.
• Format: Article
• Language: English
• Subjects: Metallothionein; Paraquat Oxidative stress Metallothionein-null mouse; Radical scavenger
• ISSN: 1382-6689; 1872-7077
• DOI: 10.1016/1382-6689(96)00011-7

Using transgenic mice in which metallothionein (MT)-I and MT-II genes, we have studied a putative role of MT as a free radical scavenger against paraquat, a free radical generator. Male mice were injected s.c. with paraquat (PQ) at a single dose of 40 or 60 mg/kg of body weight (b.w.). Two of the six MT-null mice died within 16 h at the dose of 60 mg PQ/kg. b. w. PQ administration increased hepatic MT concentration in the normal mice (C57BL/6J), but not in the MT-null mice. The lipid peroxidation (LP) determined by thiobarbituric acid-reactive substance formation was increased by PQ in the liver of normal and MT-null mice, and the enhanced level was greater in the MT-null mice than in the C57BL/6J mice. Administration of PQ significantly increased blood urea nitrogen only in the MT-null mice, indicating renal damage. Without paraquat administration, the hepatic concentration of non-protein sulphydryl compounds was less in the MT-null mice than in the C57BL/6J mice, and the basal level of LP was higher in the MT-null mice than in the C57BL/6J mice. The present results support the notion that MT plays an antioxidative role against paraquat insult under physiological conditions.