CHANGES INDUCED BY CADMIUM ADMINISTRATION ON THYROXINE DEIODINATION AND SULFHYDRYL-GROUPS IN RAT-LIVER

The effects of cadmium on 5'-deiodination of thyroxine (T4) by rat liv er and on the hepatic concentration of non-protein sulfhydryl groups ( NPSH) were studied in Wistar rats of 200-250 g body weight. A group of ten rats was injected with cadmium chloride (300 mug/100 g body weigh t i.p.) daily for 4 days. Another group of six rats received, in addit ion, dithiothreitol (DTT; 1 mg/100 g body weight i.p.) daily for the s ame period. A group of eight normal untreated rats served as control. T4 deiodination was also determined in aliquots of liver from untreate d rats, with cadmium (2 or 5 mmol/l) and with or without DTT (0, 2.5, 5 or 10 mmol/l) plus 1 muCi I-125-labelled T4. Hepatic NPSH were measu red by a colorimetric method employing dithioldinitrobenzoic acid. Hom ogenates were incubated for 90 min at 37-degrees-C and chromatographed in a tertiary amyl alcohol : hexane : ammonia (2 mol/l) (10 : 1 : 12) system. Cadmium-injected rats showed a significant (P<0.01) decrease in T4 deiodination and in the generation of I-125 (p<0.01) and tri-iod othyronine (T3) (P<0.02). NPSH were also decreased (P<0.02). Administr ation of DTT restored T4 deiodination and NPSH to normal. In-vitro add ition of cadmium or DTT to normal rat liver homogenates induced simila r effects on the degradation of T4. Serum concentrations of T4 (P<0.01 ) and T3 (P<0.01) declined significantly in cadmium-injected rats, whe reas DTT administration failed to normalize serum hormone levels. -The data suggest that cadmium may have decreased, 5'-deiodinating activit y through binding to sulfhydryl groups of 5'-deiodinase as it does in other enzymes. The effects on serum T4 concentrations may be unrelated to those on 5'-deiodinase.