Thyroid Function in a Uremic Rat Model

Lim, Victoria S.; Henriquez, Carlos; Seo, Hisao; Refetoff, Samuel; Martino, Enio

doi:10.1172/jci109963

Cited by 65 publications

(12 citation statements)

References 34 publications

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“…Moreover, analysis of covariance established that only for one spot, spot 8, could the differences between groups be accounted for by food intake alone. The possibility that the genomic alterations were due to a lowering of circulating T3 was explored in view of previous reports by Lim et al suggesting that subtotal nephrectomy results not only in a lower circulating T3 but also in diminished activity of hepatic a-GPD and ME (5). These authors, therefore, proposed that the nephrectomized animal was a potentially useful model of the clinical "low T3 syndrome" that characterizes many chronic illnesses in man (24).…”

Section: Discussionmentioning

confidence: 99%

“…This model was of special interest to us since the decreased food intake and growth retardation that accompany it reflect similar phenomena in the clinical uremic syndrome (4). Moreover, a recent report by Lim et al (5) indicates that the level of circulating triiodothyronine (T3)1 is reduced in the chronically partially ne-phrectomized rat, as has been observed in azotemic man (6). This report also suggested that in the rat model the reduction in circulating T3 leads to tissue hypothyroidism, as reflected by reduced activities of hepatic alpha-glycerolphosphate dehydrogenase (a-GPD) and malic enzyme (ME).…”

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confidence: 89%

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Hepatic messenger ribonucleic acid activity profiles in experimental azotemia in the rat. Relationship to food intake and thyroid function.

Kinlaw¹,

Schwartz²,

Mariash³

et al. 1984

J. Clin. Invest.

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A b:s tract. We have studied the hepatic messenger RNA (mRNA) activity profile in chronically azotemic rats and sought to determine whether the observed changes could be mediated either by reduced food intake or diminished thyroid function at the tissue level. mRNA activity profiles were produced by twodimensional gel electrophoretic separation of radioactively labeled products of an in vitro reticulocyte lysate system which had been programmed by hepatic RNA. Of the -240 translational products identified in this system, seven sequences were consistently altered in azotemia. In pair-fed animals six of these also decreased, but the alterations in three were depressed to a significantly lesser extent in the pair-fed group. Moreover, analysis of covariance suggested that food intake could account for the differences in only one sequence. The possibility that the mRNA activity profile in azotemia could represent the effects of diminished thyroid function was minimized by the finding that the reductions in plasma thyroxine (T4) and triiodothyronine (T3) levels observed were due largely to reduced plasma protein binding, with maintenance of the mean free T4 and free T3 concentrations within the normal range. The changes in only one mRNA sequence could be related to free T3 levels alone. Our findings, therefore, indicate that

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 89%

Hepatic messenger ribonucleic acid activity profiles in experimental azotemia in the rat. Relationship to food intake and thyroid function.

Kinlaw¹,

Schwartz²,

Mariash³

et al. 1984

J. Clin. Invest.

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“…Plasma was obtained by centrifugation (2500 ϫ g, 10 min, 4°C) and red cells were washed twice prior to being resuspended to the original volume in NaCl (0.9%). Livers were perfused in situ with chilled 0.15 M KCl and hepatic microsomes were prepared by the method of Lim et al [16]. Plasma and the remaining liver tissue were immediately snap frozen in liquid nitrogen and stored at Ϫ70°C.…”

Section: Animals and Dietsmentioning

confidence: 99%

Anthocyanin-rich extract decreases indices of lipid peroxidation and DNA damage in vitamin E-depleted rats

Ramírez-Tortosa

Andersen

Gardner³

et al. 2001

Free Radical Biology and Medicine

224

114

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Abstract-Anthocyanins are secondary plant metabolites responsible for the blue, purple, and red color of many plant tissues. The phenolic structure of anthocyanins conveys marked antioxidant activity in model systems via donation of electrons or hydrogen atoms from hydroxyl moieties to free radicals. Dietary intakes of anthocyanins may exceed 200 mg/day, however, little is known about their antioxidant potency in vivo. Consequently, the aim of this study was to establish whether anthocyanins could act as putative antioxidant micronutrients. Rats were maintained on vitamin E-deficient diets for 12 weeks in order to enhance susceptibility to oxidative damage and then repleted with rations containing a highly purified anthocyanin-rich extract at a concentration of 1 g/kg diet. The extract consisted of the 3-glucopyranoside forms of delphinidin, cyanidin, petunidin, peonidin, and malvidin. Consumption of the anthocyaninrepleted diet significantly improved (p Ͻ .01) plasma antioxidant capacity and decreased (p Ͻ .001) the vitamin E deficiency-enhanced hydroperoxides and 8-Oxo-deoxyguanosine concentrations in liver. These compounds are indices of lipid peroxidation and DNA damage, respectively. Dietary consumption of anthocyanin-rich foods may contribute to overall antioxidant status, particularly in areas of habitually low vitamin E intake.

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“…It would be of considerable interest, therefore, to test the adequacy of this assumption by analyzing the mRNA profile in animal models of nonthyroidal disease such as the tumor-bearing rat (45) and the uremic rat (46). Such studies could conceivably APPENDIX Table I, when nuclear sites are fully saturated by injected T3 for the first day, the necessary but not sufficient (compatible) criteria require that the value at the end of the first day of starvation in euthyroid animals treated with T3, (ES,)', should equal or exceed the value in the euthyroid fed animal EF.…”

Section: Discussionmentioning

confidence: 99%

Starvation and hypothyroidism exert an overlapping influence on rat hepatic messenger RNA activity profiles.

Carr¹,

Seelig²,

Mariash³

et al. 1983

J. Clin. Invest.

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A B S T R A C T To assess the effect of starvation and to explore the potential interrelationship of starvation and thyroid status at the pretranslational level, we have analyzed by two-dimensional gel electrophoresis, the hepatic translational products of starved and fed euthyroid and hypothyroid rats. 5 d of starvation resulted in a statistically significant change in 27 of 240 products visualized, whereas hypothyroidism caused a change in 20, both in comparison with the fed euthyroid state. Of considerable interest was that 68% of all changing messenger (m)RNA sequences were common to the hypothyroid and starved groups and showed the same directional shift. Further, both starvation and hypothyroidism yielded comparable decreases in total hepatic cytoplasmic RNA content. Although it has been well established that the level of circulating triiodothyronine (T3) and the level of hepatic nuclear receptors fall in starvation, this reduction cannot account for the observed decrease of total hepatic RNA nor for all of the alterations in the concentrations of specific mRNA sequences. Thus, administration of T3 to starved animals in a dose designed to occupy all nuclear T3 receptors fails to prevent the fall in total RNA and the majority of starvation-induced changes in the level of mRNA sequences. Moreover,The results of this study were reported in part at the Na- (1)(2)(3)(4)(5)(6)(7)(8) and also a decrease in hepatic nuclear T3 receptors in the rat (8)(9)(10)(11)(12). Associated with the effect of starvation on T3 receptor capacity and content are alterations in the incremental response of two hepatic enzymes, malic enzyme (ME) and a-glycerol phosphate dehydrogenase (a-GPD) to a given dose of T3 (8). Starvation and hypothyroidism are known to impair protein synthesis (13)(14)(15) and to result in a decrease in hepatic protein and RNA content (16,17).

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Thyroid Function in a Uremic Rat Model

Cited by 65 publications

References 34 publications

Hepatic messenger ribonucleic acid activity profiles in experimental azotemia in the rat. Relationship to food intake and thyroid function.

Hepatic messenger ribonucleic acid activity profiles in experimental azotemia in the rat. Relationship to food intake and thyroid function.

Anthocyanin-rich extract decreases indices of lipid peroxidation and DNA damage in vitamin E-depleted rats

Starvation and hypothyroidism exert an overlapping influence on rat hepatic messenger RNA activity profiles.

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