Roger Truchot

Liver microsome phospholipids and cytochrome P.450 conceptration in phenobarbital treated rats fed on different diets

Liver microsomal concentration of cytochrome P.450 is increased in animals which are fed diets rich in polyunsaturated fatty acids. On the other hand, the effects of phenobarbital are more important when the dietary fat is more unsaturated. The unsaturation index in liver microsomal phosphatidylcholines depends on the unsaturation of the dietary fats. The treatment with phenobarbital constantly results in a decrease of the unsaturation index of fatty acids both in lecithins and cephalins. The importance of the liver microsomal cytochrome P.450 increase and the importance of the unsaturation index decrease in liver microsomal lecithins, both promoted by phenobarbital, are in good agreement.

Effect of thyroid status and cold stress on tyrosine hydroxylase activity in adrenal gland and brown adipose tissue

Abstract A tyrosine hydroxylase activity (THa) of 1.4 nanomoles DOPA formed per hour per mg of protein has been found in brown adipose tissue homogenate; a value of 30.3 nanomoles was found in the corresponding adrenal homogenate. The THa of brown adipose tissue of normal rat increases markedly upon intermittent exposure to cold temperature and is greatly increased in the thyroidectomized rat. In adrenal gland there is, upon intermittent cold stress, an increase in the THa of normal and of thyroidectomized rats, but no increase in the THa of animal receiving triiodothyronine.

Mecanisme d'action de l'acide iodo-4-salicylique sur la respiration des mitochondries isolees

Abstract The mechanism of action of 4-iodosalicylic acid on oxidative phosphorylation in isolated rat liver mitochondria was studied. 4-Iodosalicylic acid reversed oligomycin inhibition of respiration in state 3 mitochondria. In a state uncoupled by 2,4-dinitrophenol. however, the O 2 consumption rate was lowered by the iodocompound. The Lineweaver Burk plot of 4-iodosalicylic acid inhibition of the rate of O 2 consumption with variable concentrations of succinate in the presence of ADP, was represented by straight lines. The inhibition was noncompetitive. With mitochondria in state 3, double wavelength spectrophotometric analysis of oxidoreduction states of respiratory coenzymes, showed that 4-iodosalicylic acid increased the oxidation of all components of the electron transport chain, in spite of the fact that it inhibited the oxygen consumption rate. In conclusion 4-iodosalicylic acid may be considered as an uncoupling agent, for its effects are similar in some aspects to those of 2,4-dinitrophenol. It is possible that there are at least two distinct sites at which the iodophenol can inhibit respiration; one site is probably in the respiratory chain and the other, more important, related with the coupling of high-energy intermediates.

Effets de nouveaux derives guanidyles et de diverses amidinoalkylurees sur les oxydophosphorylations

Abstract The effect on respiration of rat liver mitochondria by two classes of compounds was studied. The first contained the mono- and di-guanide derivatives of phenylethylamine and 4-hydroxyphenylethylamine. When mitochondria were in state 4 with succinate the rate of oxygen consumption was reduced with diguanides and also with the diiodomonoguanide derivative but was increased slightly with the noniodinated monoguanides. In state 3, all the compounds, but especially the 3,5-iodinated derivatives inhibited respiration. The other group of products were mono- (nonyl, decyl and undecyl) and the di(dibutyl, dioctyl and amylhexyl) alkylamidinoureas. All compounds stimulated respiration of mitochondria in state 4, the undecyl derivative being the most potent, the dialkylated being a little less active. All the products inhibited respiration in state 3. It appears that the group is essential if a compound is to influence mitochondrial respiration. Adjacent group can be either CH 2 as in phenylethylamine derivatives or CO as in amidinoalkylureas.

Influence des acides hydroxybenzoïques et de leurs derives iodes sur la respiration des mitochondries isolees

Abstract The effects of ten benzoic acid derivatives belonging to two chemical series on rat liver mitochondrial respiration were studied. The first series included 2-hydroxybenzoic acid and its iodinated derivatives. Oxygen uptake of state 4 mitochondria with succinate or β-hydroxybutyrate as substrate was stimulated by all the compounds but the iodinated derivatives, especially 4-iodosalicyclic acid were the most potent. All the compounds in this series however inhibited the oxygen consumption of mitochondria in state 3. In the presence of ascorbic acid and tetramethylphenylenediamine as respiratory substrate, salicylic acid and its iodinated derivatives had no effect. The second series included analogs of 2-hydroxybenzoic acid and some of their iodinated derivatives. Compounds with a hydroxyl group in position 3 or 4 or with an amino group in position 2 did not affect oxygen uptake of state 4 mitochondria with succinate as substrate, but a stimulation was observed with their iodinated derivatives. All the compounds inhibited the oxygen consumption of mitochondria in state 3. Similar results were obtained with β-hydroxybutyrate as substrate. Substitution by a hydroxyl group in position 2 of benzoic acid was essential therefore to uncouple oxydative phosphorylation in mitochondria. Iodination of any compound always increased respiratory properties.

Isopropyldiiodothyronine and α-methylthyroxine: Comparison of their in vitro and in vivo effects with those of thyroid hormones

Abstract The in vivo and d in vitro effects of the two thyroid hormone analogs 3,5-diiodo-3′-isopropyl- L -thyronine (IPT 2 ) and of α-methyl- DL -thyroxine (MT 4 ) have been compared to those of the thyroid hormones 3,5,3′-triiodo- L -thyronine (T 3 ) and thyroxine (T 4 ). Against purified glutamate, isocitrate and alcohol dehydrogenases IPT 2 and MT 4 exert inhibitory effects which are quite similar to those exerted by T 3 and T 4 . The effects of the analogs on isolated mitochondria follow closely those of the hormones i.e. they uncouple phosphorylations and inhibit electron transfer along the respiratory chain. When thyroidectomized animals are treated with analogs (5 nmoles/100 g/day for 15 days) their effects on two accepted parameters of thyromimetic activity, metabolic rate (BMR) and α-glycerophosphate (GPD) induction, are quite different. After IPT 2 -treatment, the rise in MR and GPD indicates a hyperthyroid state, whereas MT 4 -treatment results in very incomplete compensation of th hypothyroid state. However, treatment of the thyroidectomized animal with IPT 2 or MT 4 has the same effect on hepatic mitochondrial glutamate dehydrogenase as treatment with T 4 . A relation between thyroid state and adrenal tyrosine hydroxylase (TH) activity has been established; TH activity which decreases in the thyroidectomized animal, is brought back to normal by administration of T 4 and above normal by that of IPT 2 .