The influence of propylthiouracil and iopanoic acid on thyroid axis and glutathione peroxidases activities in selenium adequate and selenium deficient juvenile rats

U okviru ove doktorske disertacije, ispitivan je uticaj primene blokatora dejodinaza na tireoidni status selenadekvatnih i selendeficitnih juvenilnih pacova. Ogled je izveden na ukupno 128 Wistar pacova muškog pola, podeljenih u osam grupa od po 16 jedinki. Formirane su sledeće grupe: 1. Se+PTU-IA- (kontrolna grupa), 2. Se+PTU+IA+, 3. Se+PTU+IA-, 4. Se+PTUIA+, 5. Se-PTU-IA-, 6. Se-PTU+IA+, 7. Se-PTU+IA- i 8. Se-PTU-IA+. Prve četiri grupe su bile selenadekvatne (Se+) i dobijale su hranu koja je sadržala 0.334 mg selena po kilogramu hrane. Grupe pet, šest, sedam i osam su bile selendeficitne (Se-) i dobijale su 0.031 mg selena po kilogramu hrane. Kao blokatori dejodinaza su korišćeni propiltiouracil (PTU+) u dozi od 150 mg/L vode za piće i jopanoična kiselina (IA+) u dozi od 6 mg/100g TM intraperitonealno. Nakon tri i sedam nedelja tretmana žrtvovano je po 8 jedinki iz svake grupe i određivani su sledeći parametri: tiroksin (T4), trijodtironin (T3), tireostimulirajući hormon (TSH), koncentracija selena u krvi, aktivnost citosolne glutation peroksidaze eritrocita (GPx1) i aktivnost glutation peroksidaze u krvnoj plazmi (GPx3). Deficit selena doveo je do blagog pada telesne mase jedinki. Primena propiltiouracila (PTU) dovela je do značajnog pada telesne mase od 19% kod selenadekvatnih jedinki i 59% kod selendeficitnih jedinki. Pad koncentracije T4 i T3 i porast koncentracije TSH u krvnoj plazmi zabeležen je kod selenadekvatnih i selendeficitnih jedinki tretiranih sa PTU, nakon tri nedelje tretmana. Nakon sedam nedelja, koncentracije T3 u krvi svih selenadekvatnih jedinki su bile ujednačene, a kod selendeficitnih jedinki je pri upotrebi PTU bila smanjena koncentracija T3 u krvi. Istovremena upotreba jopanoične kiseline i propiltiouracila kod selendeficitnih jedinki dovela je do rasta aktivnosti GPx1 nakon tri nedelje i GPx3 nakon sedam nedelja tretmana. Upotreba PTU je dovela do gubitka korelacione zavisnosti između koncentracije selena u krvi i aktivnosti GPx1 kod selenadekvatnih i selendeficitnih jedinki nakon tri nedelje tretmana, a nakon sedam nedelja tretmana, upotreba PTU sa ili bez jopanoične kiseline je dovela do gubitka korelacione zavisnosti između koncentracije selena u krvi i aktivnosti GPx3. Negativna korelaciona zavisnost između koncentracije T3 i aktivnosti GPx1 kod selendeficitnih jedinki uočena je nakon tri nedelje tretmana, a nakon sedam nedelja između koncentracije T3 i aktivnosti GPx3.The effects of the applied deiodinase blockers on the thyroid status of selenium adequate and selenium deficient juvenile rats were studied. The experiment was carried out on 128 male Wistar rats randomly allotted to 8 groups, 16 rats each. The following groups were formed: Se+PTU-IA- (control group), 2. Se+PTU+IA+, 3. Se+PTU+IA-, 4. Se+PTU-IA+, 5. Se-PTU-IA- , 6. Se-PTU+IA+, 7. Se-PTU+IA- i 8. Se-PTU-IA+. The first four groups were selenium adequate (Se+) and were fed a diet containing 0.334 mg/Se kg feed. Groups five, six, seven and eight were selenium deficient and fed 0.031 mgSe/ kg feed. As deiodinase blockers were used propylthiouracil (PTU+) in a dose of 150 mg/L potable water and iopanoic acid (IA+) in a dose of 6 mg/kg body mass applied intraperitoneally. After 3 and 7 weeks of treatment eight rats from each group were sacrificed and the following parameters were determined: thyroxine (T4), triiodothyronine (T3), Thyroid stimulating hormone (TSH), blood selenium concentration, erythrocyte cytosolic glutathione peroxidase activity (GPx1) and blood plasma glutathione peroxidase activity (GPx3). Selenium deficiency resulted in decreased body mass. Application of propylthiouracil resulted in decreased body mass by 19% in selenium adequate and by 59% in selenium deficient rats. A decrease in T4 and T3 concentration and increased TSH concentration in the blood plasma was recorded in both selenium adequate and selenium deficient groups treated with PTU after three weeks of treatment. After seven weeks T3 concentration in all selenium adequate rats was uniform, and selenium deficient PTU treated rats had decreased blood T3 concentrations. Concurrent use of IA and PTU in selenium deficient animals resulted in increased GPx1 activity after 3 weeks and GPx3 after 7 weeks of treatment. The use of PTU led to the loss of correlation between blood selenium and GPx1 treatment in both selenium adequate and deficient rats after three weeks of treatment. After seven weeks of treatment PTU (with or without the concurrent application of IA) resulted in the loss of correlation between blood selenium concentration and GPx3 activity. A negative correlation between T3 concentration and GPx1 activity in selenium deficient rats was recorded after three weeks of treatment, and between T3 concentration and GPx3 activity after seven weeks