Diminished hepatic triiodothyronine production in Gunn rats

Abstract. The liver is a major site of conversion of thyroxine (T4) to the more active thyroid hormone 3,5,3'-triiodothyronine (T3). Hepatic T4 to T3 conversion is altered by a variety of pathological processes and pharmacological agents. We studied T4 to T3 conversion in glucuronyl transferase deficient homozygous Gunn rats because they have a hepatic enzyme abnormality which leads to hyperbilirubinaemia, and also because they have been reported to have alterations in thyroid hormone metabolism. An in vitro incubation system employing the 10 000 × g supernatant of liver homogenate was used, and T3 production was measured by radioimmunoassay. Experiments were done using substrate concentrations ranging from 0.56 to 20 μm, tissue protein in concentrations ranging from 0.625 to 20 mg and incubation times of 15 to 60 min. T3 production by liver homogenates from homozygous Gunn rats in these studies ranged from 29 to 70% of that produced by liver homogenates from phenotypically normal heterozygous Gunn rats. The deficit in hepatic T3 production by homozygous rats could not be overcome by increasing cofactor concentrations. After ultracentrifugation at 100 000 μ g, T4-5'-deiodinase activity was found primarily in the 100 000 × g sediment fraction. Homogygous rat liver 100 000 × g sediment T3 production was 55% of that of the heterozygous rat liver 100 000 × g sediment. Liver cytosol from both homozygous and heterozygous rats inhibited microsomal T4-5'-deiodinase activity similarly. Addition of unconjugated bilirubin to liver homogenates resulted in reduction of T3 production in livers from both homozygous and heterozygous rats. Thus the diminished capacity for hepatic conversion of T4 to T3 in homozygous Gunn rats may be due to inhibition of T4-5'-deiodinase activity by high endogenous levels of unconjugated bilirubin.

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Aqueous Extracts of Teucrium polium Possess Remarkable Antioxidant Activity In Vitro

Evidence-based Complementary and Alternative Medicine ◽

10.1093/ecam/nel028 ◽

2006 ◽

Vol 3 (3) ◽

pp. 329-338 ◽

Cited By ~ 52

Author(s):

Predrag Ljubuncic ◽

Suha Dakwar ◽

Irina Portnaya ◽

Uri Cogan ◽

Hassan Azaizeh ◽

...

Keyword(s):

Lipid Peroxidation ◽

Antioxidant Activity ◽

Rat Liver ◽

Antioxidant Properties ◽

Liver Homogenate ◽

Plasma Oxidation ◽

Teucrium Polium ◽

Liver Homogenates ◽

Β Carotene

Teucrium poliumL. (Lamiaceae) (RDC 1117) is a medicinal plant whose species have been used for over 2000 years in traditional medicine due to its diuretic, diaphoretic, tonic, antipyretic, antispasmodic and cholagogic properties. The therapeutic benefit of medicinal plants is often attributed to their antioxidant properties. We previously reported that an aqueous extract of the leaves and stems of this plant could inhibit iron-induced lipid peroxidation in rat liver homogenate at concentrations that were not toxic to cultured hepatic cells. Others have reported that organic extracts of the aerial components of this plant could inhibit oxidative processes. Against this background, we felt further investigation on the antioxidant action of the extract ofT. poliumprepared according to traditional Arab medicine was warranted. Accordingly, we assessed (i) its ability to inhibit (a) oxidation of β-carotene, (b) 2,2′-azobis(2-amidinopropan) dihydrochloride (AAPH)-induced plasma oxidation and (c) iron-induced lipid peroxidation in rat liver homogenates; (ii) to scavenge the superoxide ($${\hbox{ O }}_{2}^{\bullet -}$$) radical and the hydroxyl radical (OH•); (iii) its effects on the enzyme xanthine oxidase activity; (iv) its capacity to bind iron; and (v) its effect on cell glutathione (GSH) homeostasis in cultured Hep G2 cells. We found that the extract (i) inhibited (a) oxidation of β-carotene, (b) AAPH-induced plasma oxidation (c) Fe2+-induced lipid peroxidation in rat liver homogenates (IC50 = 7 ± 2 μg ml−1); (ii) scavenged $${\hbox{ O }}_{2}^{\bullet -}$$(IC50 = 12 ± 3 μg ml−1) and OH• (IC50 = 66 ± 20 μg ml−1); (iii) binds iron (IC50 = 79 ± 17 μg ml−1); and (iv) tended to increase intracellular GSH levels resulting in a decrease in the GSSG/GSH ratio. These results demonstrate that the extract prepared from theT. poliumpossesses antioxidant activityin vitro. Further investigations are needed to verify whether this antioxidant effect occursin vivo.

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Substrate specificity of iodothyronine 5′-deiodinase in rat liver homogenates and its requirements of divalent cations in vitro

Life Sciences ◽

10.1016/0024-3205(86)90575-8 ◽

1986 ◽

Vol 38 (24) ◽

pp. 2231-2238 ◽

Cited By ~ 4

Author(s):

Shinya Kobayshi ◽

Yan Gao ◽

Richard L. Ong ◽

Constance S. Pittman

Keyword(s):

Substrate Specificity ◽

Rat Liver ◽

Divalent Cations ◽

Liver Homogenates

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Differences in size, structure and function of free and membrane-bound polyribosomes of rat liver. Evidence for a single class of membrane-bound polyribosomes

Biochemical Journal ◽

10.1042/bj1680001 ◽

1977 ◽

Vol 168 (1) ◽

pp. 1-8 ◽

Cited By ~ 26

Author(s):

J C Ramsey ◽

W J Steele

Keyword(s):

Protein Synthesis ◽

Rat Liver ◽

Size Structure ◽

Large Fraction ◽

Liver Homogenate ◽

Structure And Function ◽

Structural And Functional Properties ◽

Membrane Bound ◽

And Function

Free loosely bound and tightly bound polyribosomes were separated from rat liver homogenate by salt extraction followed by differential centrifugation, and several of their structural and functional properties were compared to resolve the existence of loosely bound polyribosomes and verify the specificity of the separation. The free and loosely bound polyribosomes have similar sedimentation profiles and polyribosome contents, their subunit proteins have similar electrophoretic patterns and their products of protein synthesis in vitro show a close correspondence in size and amounts synthesized. In contrast, the tightly bound polyribosomes have different properties from those of the free and loosely bound polyribosomes; their average size is significantly smaller; their polyribosome content is higher; their 60 S-subunit proteins lack two components and contain four or more components not found elsewhere; their products of protein synthesis in vitro differ in size and amounts synthesized. These observations show that rat liver membranes entrap a large fraction of the free polyribosomes at low salt concentrations and that these polyribosomes are similar to those of the free-polyribosome fraction and are different from those of the tightly bound polyribosome fraction in size, structure and function.

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Metabolism in vitro of n-methylamphetamine with rat liver homogenates

Biochemical Pharmacology ◽

10.1016/0006-2952(77)90242-8 ◽

1977 ◽

Vol 26 (11) ◽

pp. 1043-1049 ◽

Cited By ~ 17

Author(s):

Ronald T. Coutts ◽

Susan H. Kovach

Keyword(s):

Rat Liver ◽

Liver Homogenates

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A STUDY ON THE "IN VITRO" SYNTHESIS OF CITRULLINE: PART II. EFFECT OF GLUTAMIC ACID AND DERIVATIVES IN THE PRESENCE OF FUMARIC ACID

Canadian Journal of Biochemistry ◽

10.1139/o64-142 ◽

1964 ◽

Vol 42 (9) ◽

pp. 1325-1330 ◽

Cited By ~ 2

Author(s):

René Charbonneau ◽

Louis Berlinguet

Keyword(s):

Glutamic Acid ◽

Rat Liver ◽

Fumaric Acid ◽

Liver Homogenate ◽

Particulate Fraction ◽

In Vitro Synthesis ◽

System L ◽

Acyl Derivatives

The role of N-carbamyl, N-acetyl, and L-glutamic acids with and without fumaric acid on the "in vitro" synthesis of citrulline was studied by using a particulate fraction obtained from a rat liver homogenate and a partially purified citrulline-synthesizing enzyme system. In the presence of a particulate fraction of rat liver homogenate, N-carbamyl and N-acetyl-L-glutamic acids are unable to replace L-glutamic acid, which is essential for citrulline biosynthesis. However, in the presence of fumaric acid, they both give a better synthesis of citrulline than L-glutamic acid alone. It is postulated that the acyl derivatives serve only in the transport of "activated CO2" whereas fumaric acid enters the citric acid to furnish the essential ATP molecules. Glutamic acid would be able to perform both functions. However, in the presence of a system containing partially purified citrulline-synthesizing enzymes, L-glutamic acid is unable to replace N-carbamyl and N-acetyl-L-glutamic acids with or without fumaric acid. In such a system, L-glutamic acid cannot serve in the transport of "activated CO2". It is postulated that L-glutamic acid must be acetylated prior to its utilization in this respect.With the particulate fraction of rat liver homogenate, N-allyl aspartic acid inhibits totally the synthesis of citrulline both in the presence and absence of fumaric acid with or without glutamic or N-acetyl glutamic acids. It probably interferes with the transport of "activated CO2".

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Effect of excessive iodine exposure on the placental deiodinase activities and Hoxc8 expression during mouse embryogenesis

British Journal Of Nutrition ◽

10.1017/s0007114507691909 ◽

2007 ◽

Vol 98 (1) ◽

pp. 116-122 ◽

Cited By ~ 8

Author(s):

Xue F. Yang ◽

Jian Xu ◽

Huai L. Guo ◽

Xiao H. Hou ◽

Li P. Hao ◽

...

Keyword(s):

Thyroid Hormone ◽

Thyroid Hormone Receptor ◽

Skeletal Development ◽

Gene Expression Pattern ◽

Skeletal Malformation ◽

Thyroid Hormone Metabolism ◽

Deiodinase Activity ◽

Excessive Iodine ◽

Total Thyroxine

Excessive iodine induces thyroid dysfunction. However, the effect of excessive iodine exposure on maternal–fetal thyroid hormone metabolism and on the expression of genes involved in differentiation, growth and development is poorly understood. Since a thyroid hormone receptor response element was found in the Hoxc8 promoter region, Hoxc8 expression possibly regulated by excessive iodine exposure was firstly investigated. In the present study, Balb/C mice were given different doses of iodine in the form of potassium iodate (KIO3) at the levels of 0 (sterile water), 1·5, 3·0, 6·0, 12·0 and 24·0 μg/ml in drinking water for 4 months, then were mated. On 12·5 d postcoitum, placental type 2 and type 3 deiodinase activities and fetal Hoxc8 expression were determined. The results showed that excessive iodine exposure above 1·5 μg/ml resulted in an increase of total thyroxine and a decrease of total triiodothyronine in the serum of maternal mice, which was mainly associated with the inhibition of type 1 deiodinase activity in liver and kidney. Placental type 2 deiodinase activity decreased, showing an inverse relationship with maternal thyroxine level. Hoxc8 mRNA and protein expression at 12·5 d postcoitum embryos were down regulated. Because Hoxc8 plays an important role in normal skeletal development, this finding provides a possible explanation for the skeletal malformation induced by excessive iodine exposure and also provides a new clue to study the relationship between iodine or thyroid hormones and Hox gene expression pattern.

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INHIBITION OF CHOLESTEROL FORMATION BY RAT LIVER HOMOGENATES

Canadian Journal of Biochemistry and Physiology ◽

10.1139/o55-020 ◽

1955 ◽

Vol 33 (2) ◽

pp. 135-138 ◽

Cited By ~ 10

Author(s):

B. B. Migicovsky

Keyword(s):

Vitamin A ◽

Rat Liver ◽

Cholesterol Synthesis ◽

Liver Homogenate ◽

Inhibitory Factor ◽

Normal Rat ◽

Liver Homogenates

The inability of liver homogenates, from starved and vitamin A deficient rats, to synthesize cholesterol is illustrated. A possible reason for this phenomenon is that these preparations inhibit cholesterol synthesis when added to a liver homogenate from a normal rat. The inhibitory factor or factors are present in both the supernate and residue portions of the homogenate, although the residue matter is more inhibitory.

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