Effects of the novel thyroid hormone analogues, SKF L-94901, DIBIT, and 3'-AC-T2 on mitochondrial function

The effects of L-T3 (3,3',5-triiodo-L-thyronine) and three novel analogues, SKF L-94901 (3,5-Dibromo-3'-pyridazinone-L-thyronine), Dibit (3,5-Dibromo-3'-isopropyl-L-thyronine), and 3'-Ac-T2(3'-Acetyl-3,5,-Diiodo-L-thyronine), on mitochondrial parameters were determined in hypothyroid rats. The parameters include the 24 hour hormone-induced changes in the bc1 complex and in the proton permeability of the mitochondrial inner membrane. The cardiac sparing analogue, SKF L-94901, had no effect on mitochondrial respiration or proton permeability; but the analogue did increase a-glycerophosphate dehydrogenase activity, mitochondrial ubiquinone content, and altered the bypass respiration in the bc1 complex. Dibit also did not increase respiration significantly but did change the other parameters. 3'-Ac-T2 increased respiration, mitochondrial ubiquinone content, proton permeability, enzyme activity and altered the bypass of the Antimycin A blockage in the bc1 complex.