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Folic Acid Alleviates Oxidative Stress and Hyperhomocysteinemia Involved in Liver Dysfunction of Hypothyroid Rats
Ehab Tousson1,
, Wafaa Ibrahim2, Afrah F. Salama3, Wesam M. Hussein3
1Department of Zoology, Faculty of Science, Tanta University, Egypt
2Department of medical Biochemistry, Faculty of Medicine, Tanta University, Egypt
3Biochemistry Section, Department of Chemistry, Faculty of Science, Tanta University, Egypt
Abstract
Thyroid hormones are essential for growth and development of the liver. This study evaluated some biochemical alterations in post-pubertal hypothyroidism and its impact on liver functions. Additionally, the ameliorating role of folic acid supplementation was investigated. Fifty male albino rats were randomly divided into five groups (group I, control; group II, folic acid; group III, 0.05% propylthiouracil-induced hypothyroid rats; group IV, Co-treatment; group V post-treatment). There was a significant decrease in plasma T3, body weight, fluid and food intakes, folic acid, ALT, total thiol and tFRAP in hypothyroid rats as compared to control group. On the other hand, a significant increase in TSH, relative liver weight, plasma of total homocysteine, serum total protein, AST, total serum bilirubin, cholesterol and tMDA in hypothyroid rats as compared to control group. This reflects hyperhomocysteinemia and oxidative stress associated with hypothyroid state. Folic acid supplemented after restoration of the euthyroid state presented better amelioration over its concurrent supplementation. If confirmed in human beings, our results could propose that folic acid can be used as an adjuvant therapy in hypothyroidism disorders with thyroxin replacement therapy.
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Keywords: hypothyroidism, liver, oxidative stress, folic acid, PTU
American Journal of Biomedical Research, 2014 2 (4),
pp 70-76.
DOI: 10.12691/ajbr-2-4-3
Received September 27, 2014; Revised October 13, 2014; Accepted November 20, 2014
Copyright © 2013 Science and Education Publishing. All Rights Reserved.Cite this article:
- Tousson, Ehab, et al. "Folic Acid Alleviates Oxidative Stress and Hyperhomocysteinemia Involved in Liver Dysfunction of Hypothyroid Rats." American Journal of Biomedical Research 2.4 (2014): 70-76.
- Tousson, E. , Ibrahim, W. , Salama, A. F. , & Hussein, W. M. (2014). Folic Acid Alleviates Oxidative Stress and Hyperhomocysteinemia Involved in Liver Dysfunction of Hypothyroid Rats. American Journal of Biomedical Research, 2(4), 70-76.
- Tousson, Ehab, Wafaa Ibrahim, Afrah F. Salama, and Wesam M. Hussein. "Folic Acid Alleviates Oxidative Stress and Hyperhomocysteinemia Involved in Liver Dysfunction of Hypothyroid Rats." American Journal of Biomedical Research 2, no. 4 (2014): 70-76.
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1. Introduction
Thyroid hormones has multiple effects on liver function including stimulation of enzymes regulating lipogenesis and lipolysis as well as oxidative processes [1], also it stimulates protein turnover by stimulating both protein synthesis and degradation, in addition to increase gene expression with concomitant increases in protein synthesis and enzyme activity [2]. Thyroid hormones stimulates turnover of glucose, accordingly it has been found that the cycling between glycogenolysis and gluconeogenesis is stimulated by thyroid hormones [3].
Hypothyroidism has been reported to cause mild hyperhomocysteinaemia (increased homocysteine concentration in the blood) [4-8][4]. The mechanism by which hypothyroidism causes mild hyperhomocysteinaemia is not clear but altered remethylation is likely to be involved. Additionally, complex changes in folic acid metabolism occur in thyroid dysfunction with increases in tetrahydrofolate and decreases in methyltetrahydrofolate in hypothyroid rat liver [9]. Alteration in thyroid hormone level is also known to modulate functions of several tissues in adult animals by modulating their antioxidant defenses [4-8,10-13]. Overt Thyroid dysfunctions are frequently associated with abnormalities of biochemical liver tests and in severe forms with histologically evident hepatocellular damage the activity of hepatic lipase is decreased [14]. Hypothyroid animals have decreased metabolic rate with decreased hepatocytes oxygen consumption [15].
Reversible abnormalities of liver function tests are common, although usually mild, in hypothyroidism. In addition, there is a significant decrease in gluconeogenesis [16]. Hypothyroid patients have specific defects in hepatic handling of amino acids resulting in decreased urea nitrogen generation [17].
Hypothyroidism may alter several critical steps in cholesterol and bile acid synthesis [18]. In addition, thyroid hormone modifies lipoprotein metabolism in the liver [19]. It is unclear whether this is a direct thyroid effect on liver enzymes or secondary to altered intestinal handling of cholesterol and bile acids [20].
There is also evidence that hypothyroidism may directly affect the liver structure or function. Hypothyroidism has been associated in a few case reports with cholestatic jaundice attributed to reduced bilirubin and bile excretion. The triad of reduced bilirubin excretion, hypercholesterolemia and hypotonia of the gall bladder seen in hypothyroidism increases the incidence of gallstones [21].
Folic acid, also known generically as folate is a member of the B-complex family of vitamins, works in concert with vitamin B12. Folic acid functions primarily as a methyl-group donor involved in many important body processes, including DNA synthesis. Therapeutically, folic acid is instrumental in reducing homocysteine levels. Moreover, this vitamin also has antioxidant properties [22]. So, therefore this work aimed to study the effect of hypothyroidism on liver, total plasma homocysteine level and oxidative stress parameters, aid to assess the possible effect of folic acid in reducing these changes.
2. Materials and Methods
The experiments were performed on fifty male albino rats (Rattus norvigicus) weighing (120 g ±10 g) and of 6-7 week’s age. The rats were kept in the laboratory for one week before the experimental work and maintained on a standard diet and water available ad libitum. The temperature in the animal room was maintained at 23±2C with a relative humidity of 55±5%. Light was on a 12:12 hr light -dark cycle. The experimental protocol was approved by Local Ethics Committee and Animals Research. The rats were randomly and equally divided into five groups (10 animals each).
Group 1: (G1) Control group in which, rats never received any treatment.
Group 2: (G2) Folic acid group in which, rats received clear water for two week then folic acid (El Nasr Pharmaceutical Chemicals Co.; 0.011 µmol/g of body weight/day) for four weeks according to Salama et al. [8].
Group 3: (G3) Hypothyroid rats group in which, rats received 0.05% 6-n-propyl-2-thiouracil (PTU) in drinking water for 6 weeks according to Tousson et al. [11].
Group 4: (G4) Co-treatment group in which, rats received 0.05% PTU in drinking water and folic acid simultaneously according to Salama et al. [8]. Rats received PTU for six weeks as in hypothyroid rats group. However, folic acid was administered orally for 4 weeks (form 2nd week to 6th week) after evidence of hypothyroidism had been established at the end of the second week.
Group 5: (G5) Post treatment group in which, rats received 0.05% PTU in drinking water for 6 weeks as in hypothyroid rats group. Additionally, folic acid was administered for another 4 weeks (form 7th week to 10th week) while PTU was withdrawn after the sixth week to return to the euthyroid state.
During the course of treatment, daily fluid consumption, body weight gain, and feed consumption were recorded periodically. At the end of the experimental period, rats were euthanized. Blood samples were individually collected from each rat in heparinized and non heparinized glass tubes to estimate some parameters in plasma and serum. Also liver were quickly removed and weighed after the removal of the surrounding connective tissues carefully and washed in saline and homogenized for assessment of biochemical parameters.
Biochemical investigations: Serum T3 was assayed by using commercial test supplied by the Diagnostic systems Laboratories (Taxes, USA) according to the method of Chopra et al. [23]. Serum TSH was assayed by using commercial Kit supplied by Coat-A-Count TSH IRMA (Los Angeles, USA) according to the method of Engall [24]. AST and ALT activities in serum were assayed by using commercial kit that was supplied by Randox (Egypt) according to the method of Rietman and Frankel [25]. Concentration of bilirubin was spectrophotometrically determined using commercial diagnostic kits supplied by Human (German) according to the method of Jendrassik and Gróf [26]. Concentration of total protein was spectrophotometrically determined using commercial diagnostic kits supplied by Diamond (Egypt) according to the method of Bowers and Wong [27]. Cholesterol concentration was assayed by using commercial kit that was supplied by Spinreact (Spain) according to the method of Allain et al. [28].
Blood plasma was analyzed with High-Performance Liquid Chromatography (HPLC) to determine folic acid and total homocysteine (tHcy). The HPLC instrument was Agilent 1200 series HPLC system from Agilent Technologies (USA). Folic acid was determined by HPLC according to the method of Amidzic et al. [29]. Total plasma homocysteine was determined by HPLC according to the method of Jayatilleke and Shaw [30].
MDA in liver was estimated by the method of Placer et al. [31] using 1,1,3,3-tetramethoxypropane (Fluka Chemical Company) as MDA standard. Ferric reducing ability of liver homogenate which represent total antioxidant capacity (TAC) was [32].
2.1. Statistical AnalysisData were expressed as mean values ± SEM and statistical analysis was performed using one-way analysis of variance (ANOVA) to assess significant differences among treatment groups. The criterion for statistical significance was set at p < 0.05. All statistical analyses were performed using SPSS statistical version 16 software package (SPSS® Inc, USA).
3. Results
In order to ensure that PTU induced hypothyroidism we determined the serum T3 and TSH through the dose period. Table 1 showed that the serum T3 levels in hypothyroid rats and in co-treated hypothyroid rats with folic acid was significantly lower when compared with the control group; also post treated hypothyroid rats with folic acid were significantly higher when compared with the hypothyroid rats. On the other hand, Table 1 showed that serum TSH levels in hypothyroid rats and co-treated hypothyroid rats with folic acid were significantly higher than those found in the control group; also post treated hypothyroid rats with folic acid were significantly lower when compared with the hypothyroid rats.
Table 1 showed that, Plasma Hcy in hypothyroid rats were significantly higher when compared with the control group, also treatment of hypothyroid rats with folic acid (during and after inducing hypothyroidism) were insignificantly lower when compared with the hypothyroid rats (Table 1). Table 2 showed that, body weight gain were significantly lower in hypothyroid rats and in hypothyroid rats which co treated with folic when compared with the control and post treated folic acid groups. Also relative liver weight (RLW) were significantly lower in hypothyroid rats and in co-treated hypothyroid rats with folic acid when compared with the control and post treated hypothyroid rats with folic acid. The fluid intake in hypothyroid rats and in treated hypothyroid rats with folic acid groups was significantly lower than control group. The food intake in hypothyroid rats and in treated hypothyroid rats with folic acid groups were significantly lower than control (Table 2).
Table 1. The changes in the concentration of plasma T3, TSH, folic acid and Hcy levels in different groups under study
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Table 2. Changes in body weight, relative liver weight (RLW), food and fluid intake in different groups under study
, food and fluid intake in different groups under study)
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View current table in a new windowTable 3 showed that serum ALT showed non significant changes in hypothyroid group when compare with other groups. AST in hypothyroid, co-treatment and post-treatment groups showed significant increase as compared to control group. However, AST showed significant decrease in control group as compared to hypothyroid, co-treatment and post-treatment groups. Serum total protein in hypothyroid group showed significant increase as compared to all other groups.co-treatment and post-treated hypothyroid rats with folic acid showed significant decrease when compared with hypothyroid group (Table 3). Total serum bilirubin in hypothyroid, co-treated and post- treated groups showed non significant increase when compared with control group. Serum cholesterol in hypothyroid and in treated hypothyroid rats with folic acid showed significant increase as compared to control group. On the other hand, treated hypothyroid rats with folic acid showed significant decrease as compared to hypothyroid group (Table 3).
Table 4 showed that oxidative stress which represent by MDA in liver tissues in hypothyroid rats is significantly higher than those found in the control group; on the other hand, oxidative stress were reduced in hypothyroid groups that treated with folic acid. Also, Table 4 showed that total antioxidant capacity, total thiol and FRAP in liver tissue in hypothyroid group showed significant decrease when compared with the control and folic acid groups, also total antioxidant capacity, total thiol and FRAP in liver tissue in hypothyroid rat groups that treated with folic acid showed significant increase as compared to hypothyroid group.
Table 4. changes in the malondialdehyde (MDA) levels, ferric reducing antioxidant power (FRAP) and total thiol in liver tissue of different groups under study
 levels, ferric reducing antioxidant power (FRAP) and total thiol in liver tissue of different groups under study)
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View current table in a new windowTable 5. Correlation coefficient (r) of T3, tHcy, folic acid and liver MDA with liver FRAP, and liver total thiol in all groups under study
 of T3, tHcy, folic acid and liver MDA with liver FRAP, and liver total thiol in all groups under study)
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 with thyroid stimulating hormone (TSH) in different studied groups)
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 with albumin in different studied groups)
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 in different studied groups)
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Larger image(png format)Pearson correlation coefficient of different studied parameters in different studied groups:
In Table 5 and Figure 1- Figure 7, a significant negative correlation was detected between total T3 with TSH, tHcy in all groups. On the other hand, a significant positive correlation was detected between tHcy with AST, cholesterol and albumin in all groups. Folic acid was positive correlated with FRAP and total thiol in liver, however a negative correlation with MDA in liver tissues. However negative significant correlations were detected between folic acid with tHcy. In addition to liver MDA had significant negative correlation with liver FRAP.
4. Discussion
The present study was designed to investigate the effect of hypothyroidism on rat liver structure and functions and the possible ameliorating effect of folic acid in treatment. In order to achieve this target we made a hypothyroid state by using a reversible goitrogen (PTU) that known to decrease the conversion of peripheral T4 to T3 and thereby reduce serum T3 concentration [4, 5, 8, 11, 33]. Hypothyroid state was documented by changes in T3 and TSH. The overall changes in the thyroid hormones profile reflect the observed decline in body weight gain. The decrease in body weight gain was associated with a reduction in food and fluid consumption in groups of hypothyroidism. These findings are compatible with the results of other studies [11].
Folic acid exerts an important role over homocysteine catabolism by methyl group donation in remethylation pathway to methionine [34]. In the present study serum Hcy in hypothyroid rats were significantly higher than those found in the control, also Hcy in hypothyroid rats which treated with folic acid during and after inducing hypothyroidism were insignificantly lower than those found in the hypothyroid rats. This finding is in line with that of Diekman et al. [35] nd Ibrahim et al. [4] who reported that plasma Hcy concentrations increased in hypothyroidism and decreased in hyperthyroidism the mechanism of thyroid-induced changes in homocysteine metabolism is currently unknown. Adrees et al. [36] who observed that total Hcy levels were elevated in patients with subclinical and overt hypothyroidism. The explanation of this effect could be attributed to the reduced glomerular filtration rate in hypothyroidism which is linked to impaired renal Hcy clearance and hyperhomocysteinaemia [37]. Alternatively, changes in the concentrations or biologic activity of vitamin B12 or B6, and/or folate may occur in response to altered thyroid homeostasis [38].
Liver is a major target organ for thyroid hormone with important biological and medical implications [39]. Clinical diagnosis of disease and damage to the structural integrity of liver is commonly assessed by monitoring the status of serum AST and ALT activities. In the present study AST elevation may be attributed to myopathies which are usually associated with hypothyroidism [40]. It has been well established that thyroid hormone affects cholesterol concentration, hepatic metabolism and cholesterol synthesis [41]. In the present study, serum cholesterol in hypothyroid, co-treatment and post-treatment groups showed significant increase as compared to control group. However co-treatment and post-treatment groups showed significant decrease as compared to hypothyroid group. Hypercholesterolemia might have resulted from increased mobilization of body fat reserves as a result of increased thyrotrophic hormone level in induced hypothyroidism [42]. Moreover, hypercholesterolemia and hyperlipidemia and poor body weight have been suggested as excellent indicators of suspected hypothyroidism [43]. Thyroid hormones are predominantly considered as hormones involved in the catabolic processes of lipids [44]. Variations in the serum total cholesterol, HDL and LDL-VLDL cholesterol, and total cholesterol in the liver and muscle accounts for the variation in the activity of thyroid hormones on cholesterol biosynthesis and degradative pathways. The most noticeable fact is that hypothyroidism results in the accumulation of cholesterol in the liver and thyroid hormone treatment reduces it [44]. There are relationships between hypothyroidism and hypercholesterolemia and hyperhomocysteinemia [45]. Karmin et al. [46] suggested that homocysteine effects cholesterol production and secretion.
Total serum bilirubin in hypothyroid, co-treatment and post-treatment groups showed significant increase as compared to control and folic acid groups. The increased bilirubin levels observed in the hypothyroid group in the present study might be explained by the findings from earlier observational studies, which proposed that the activity of bilirubin UDP glucuronyl transferase is decreased, resulting in a reduction in bilirubin excretion [40], thyroid function affects bile flow and composition so bilirubin excretion decreases in hypothyroid and increases in hyperthyroid rats [47]. The liver synthesizes a number of plasma proteins so if liver was affected by hypothyroidism; these proteins would be altered. Total protein in serum of hypothyroid rats showed significant increase as compared to all other groups. Co-treatment and post-treatment groups showed significant decrease as compared to hypothyroid group. The resultant increase in inflammatory proteins and immunoglobulins may account for marginally raised serum proteins observed in hypothyroid subjects [48].
It has been well documented that thyroid dysfunction increases lipid peroxidation reactions (evidenced by the elevated MDA levels) and reactive oxygen species [49], and these match with the present study as there was significantly higher of MDA in liver homogenate of hypothyroid group when compared to the control and folic acid groups. The significant decrease in total thiol of liver homogenate in hypothyroid group compared to control group reflects increasing oxidative stress and reduction of antioxidants effectiveness with hypothyroidism [50]. The significant increase in total thiol of liver homogenate in co-treatment as compared to hypothyroid group was explained by the role of folic acid in restoring FRAP without restoration of euthyroid state as presented here. However liver homogenate of post-treatment show significant increase in total thiol as compared to hypothyroid group, this was explained by the role of folic acid and normal thyroid hormone. This finding confirms what previously mentioned that thyroid hormones regulate protein, and antioxidant enzymes synthesis and degradation [4, 13].
Reference
| [1] | Strait KA, Kinlaw WB, Mariash, CN, Oppenheimer JH. Kinetics of induction by thyroid hormone of the two hepatic mRNAs coding for cytosolic malic enzyme in the hypothyroid and euthyroid states. Evidence against an obligatory role of S14 protein in malic enzyme gene expression. J Biol Chem 1989; 264; 19784-9. | ||
 In article | |||
| [2] | Morrison WL, Gibson JN, Jung RT. Skeletal muscle and whole body protein turnover in thyroid disease. Eur. J. Clin, 1988; 18; 62-8. | ||
| In article | CrossRef | ||
| [3] | Rochon C, Tauveron I, Dejax C. Response of glucose disposal to hyperinsulinaemia in human hypothyroidism and hyperthyroidism. Clin Sci 2003; 104; 7-15. | ||
| In article | CrossRef | ||
| [4] | Ibrahim W, Tousson E, Ali EM, Mansour MA. Folic acid alleviates oxidative stress and hyperhomocysteinemia involved in testicular dysfunction of hypothyroid rats. General and Comparative Endocrinology 2011; 174; 143-9. | ||
| In article | CrossRef | ||
| [5] | Ibrahim W, Tousson E, El-Masery T, Arafa N, Akela M. The effect of folic acid as an antioxidant on the hypothalamic monoamines in experimentally induced hypothyroid rat. Toxicology and Industrial Health 2012; 28; 253-61. | ||
| In article | CrossRef | ||
| [6] | Tousson E, Ali EM, Ibrahim W, Mansour MA. Treatment with folic acid ameliorated the histopathological alterations caused by propylthiouracil-induced hypothyroid rat testes. Toxicology and Industrial Health 2012b; 28; 566-76. | ||
| In article | CrossRef | ||
| [7] | Tousson E, Ibrahim W, Arafa N and Akela MA. Monoamine concentrations changes in the PTU induced hypothyroid rat brain and the ameliorating role of folic acid. Human & Experimental Toxicology 2012a; 31; 282-9. | ||
| In article | CrossRef | ||
| [8] | Salama AF, Tousson E, Ibrahim W and Hussein MW. Biochemical and histopathological studies in the PTU-induced hypothyroid rat kidney with reference to the ameliorating role of folic acid. Toxicology and Industrial Health 2013; 29 (7); 600-8. | ||
| In article | CrossRef | ||
| [9] | Nair CP, Viswanathan G, Noronha JM. Folate mediated incorporation of ring-2-carbon of histidine into nucleic acids: influence of thyroid hormone. Metabolism 1994; 43; 1575-8. | ||
| In article | CrossRef | ||
| [10] | Tousson E, Ali EM, Ibrahim W and Ashraf RM (2012): Histopathological and immunohistochemical alterations in rat heart after thyroidectomy and the role of hemin and ketoconazole in treatment. Biomedicine & Pharmacotherapy. 66 (2012) 627-632. | ||
| In article | CrossRef | ||
| [11] | Tousson E, Ali EM, Ibrahim W, Mansour MA. Proliferating Cell Nuclear Antigen as a Molecular Biomarker for Spermatogenesis in PTU-Induced Hypothyroidism of Rats. Reprod Sci 2011; 18; 679-86. | ||
| In article | CrossRef | ||
| [12] | Tousson E, Hafez E, Massoud A, Sweef O, Atta N. Protective role of folic acid in thyroxine-induced cardiac hypertrophy in hyperthyroid rat. Biomedicine & Aging Pathology 2013; 3; 89-95. | ||
| In article | CrossRef | ||
| [13] | Tousson E and Hafez E. Thyroxine-induced cardiac hypertrophy: Role of ascorbic acid in treatment. Biomedicine & Aging Pathology 2014; 4. | ||
| In article | |||
| [14] | Tan KC, Shiu SW, Kung AW. Effect of thyroid dysfunction on high-density lipoprotein sub fraction metabolism: roles of hepatic lipase and cholesteryl ester transfer protein. J Clin Endocrinol Metab 1998; 83; 2921-4. | ||
| In article | |||
| [15] | Liverini G, Iossa S, Barletta A. Relationship between resting metabolism and hepatic metabolism: effect of hypothyroidism and 24 hours fasting. Hor Res 1992; 38; 154-8. | ||
| In article | CrossRef | ||
| [16] | Comte B, Vidal H, Laville M, et al. Influence of thyroid hormones on gluconeogenesis from glycerol in rat hepatocytes: a dose-response study. Metabolism 1990; 39; 259-63. | ||
| In article | CrossRef | ||
| [17] | Marchesini G, Fabbri A, Bianchi GP, et al. Hepatic conversion of amino nitrogen to urea nitrogen in hypothyroid patients and upon L-thyroxine therapy. Metabolism 1993; 42; 1263-6. | ||
| In article | CrossRef | ||
| [18] | Balasubramaniam S, Mitropoulous KA, Myant NB. Hormonal Control of the Activities of Cholesterol-7hydroxylase and Hydroxy Methylglutaryl-Coa Reductase in Rats. In: Advances in bile acid research. Matern, S, Hachenschmidt, J, Back, P, et al, (eds). Stuttgart: Schattauer Verlag. P 61; 1975. | ||
| In article | |||
| [19] | Lin-Lee YC, Strobl W, Soyal S, et al. Role of thyroid hormone in the expression of apo lipoprotein A-IV and C-III Genes in rat liver. J Lipid Res 1993; 34; 249-55. | ||
| In article | |||
| [20] | Gebhart RL, Stone BG, Andreini JP, et al. Thyroid hormone differentially augments biliary sterol secretion in the rat. J Lipid Res 1992; 33; 1459-64. | ||
| In article | |||
| [21] | Inkinen J, Sand J, Nordback I. Association between common bile duct stones and treated hypothyroidism. Hepatogastroenterology 2000; 47; 919-21. | ||
| In article | |||
| [22] | Au-Yeung KW, Yip JCW, Siow YL, Karmin O. Folic acid inhibits homocysteine-induced superoxide anion production and nuclear factor kappa B activation in macrophages. Can J Physiol Pharmacol 2006; 84; 141-7. | ||
| In article | CrossRef | ||
| [23] | Chopra IJ, Solomon DH, Ho RS. A radioimmunoassay of triiodothyronine. J Clin Endocrinol 1971; 33; 865-8. | ||
| In article | CrossRef | ||
| [24] | Engall E. Methods in Enzymology. In: Methods in Enzymology. Van Vunakis H. and Langone J.J. (eds.), Vol. 70, Academic press, New York. pp 419-92; 1980. | ||
| In article | |||
| [25] | Rietman S, Frankel S. A colorimetric method for determination of serum glutamic oxaloacetic and glutamic pyruvic transaminase. Amer J Clin Pathol 1957; 28; 56-61. | ||
| In article | |||
| [26] | Jendrassik L, Gróf P. Vereinfachte photometrische Methoden zur Bestimmung des Blutbilirubins. Biochem Zeitschrift 1938; 297; 82-9. | ||
| In article | |||
| [27] | Bowers L, Wong E. Kinetic serum creatinine assays. A critical evaluation and review. Clin Chem 1980; 26; 555-61. | ||
| In article | |||
| [28] | Allain C, Poon L, Chan G, Richmond W, Fu C. Enzymatic determination of total serum cholesterol. Clin Chem 1974; 20 (4); 470-5. | ||
| In article | |||
| [29] | Amidzic R, Brboric J, Cudina O, Vladimirov S. RP-HPLC Determination of vitamins B1, B3, B6, folic acid and B12 in multivitamin tablets. J Serb Chem Soc 2005; 70 (10); 1229-35. | ||
| In article | CrossRef | ||
| [30] | Jayatilleke E, Shaw S. A high performance liquid chromatographic assay for reduced and oxidized glutathione in biological samples. Ana Biochem 1993; 214; 452-7. | ||
| In article | CrossRef | ||
| [31] | Placer ZA, Cushmann LL, Johnson BC. Estimation of products of lipid peroxidation in biochemical systems. Anal Biochem 1966; 16; 359-64. | ||
| In article | CrossRef | ||
| [32] | Benzie IF, Strain JJ. The ferric reducing ability of plasma (FRAP) as a measure of antioxidant power: the FRAP assay. Anal Biochem 1996; 239; 70-6. | ||
| In article | CrossRef | ||
| [33] | Gilbert ME, Paczkowski C. Propylthiouracil (PTU) induced hypothyroidism in the developing rat impairs synaptic transmission and plasticity in the dentate gyrus of the adult hippocampus. Dev Brain Res 2003; 145; 19-29. | ||
| In article | CrossRef | ||
| [34] | Brosnan JT, Jacobs RL, Stead LM, Brosnan ME. Methylation demand: a key determinant of homocysteine metabolism. Acta Biochim 2004; 51; 405-13. | ||
| In article | |||
| [35] | Diekman MJ, Harms MP, Endert E. Endocrine factors related to changes in total peripheral vascular resistance after treatment of thyrotoxic and hypothyroid patients. Eur J Endocrinol 2001; 144; 339-42. | ||
| In article | CrossRef | ||
| [36] | Adrees M, Gibney J, El-Saeity N, Boran G. Effects of 18 months of L-T4 replacement in women with subclinical hypothyroidism. Clin Endocrinol (Oxf) 2001; 71 (2); 298-303. | ||
| In article | CrossRef | ||
| [37] | Turhan S, Sezer S, Erden G, Guctekin A, Ucar F, Ginis Z, Ozturk O, Bingol S. Plasma homocysteine concentrations and serum lipid profile as atherosclerotic risk factors in subclinical hypothyroidism. Annu Saudi Med 2008; 28 (2); 96-101. | ||
| In article | CrossRef | ||
| [38] | Parameswaran F, Nair CP, Viswanathan G, Noronha, JM. Folate mediated incorporation of ring-2-carbon of histidine into nucleicacids: influence of thyroid hormone. Metabolism 1994; 43; 1575-8. | ||
| In article | CrossRef | ||
| [39] | 39 Simon-Giavarotti KA, Giavarotti L, Gomes, LF, Lima AF, Veridiano AM, Garcia EA. Enhancement of lindane induced liver oxidative stress and hepatotoxicity by thyroid hormone is reduced by gadolinium chloride. Free Radic Res 2002; 36; 1033-9. | ||
| In article | CrossRef | ||
| [40] | Malik R, Hodgson H. The relationship between the thyroid gland and the liver. Q J Med 2002; 95; 559-69. | ||
| In article | CrossRef | ||
| [41] | Dory L, Roheim P. Rat plasma lipoproteins and apolipoproteins in experimental hypothyroidism. J Lipid Res 1981; 22 (2); 287-96. | ||
| In article | |||
| [42] | Varghese, S, Shameena, B, Oommen, OV. Thyroid hormones regulate lipid peroxidation and antioxidant enzyme activities in Anabas testudinens (Bloch). Comp Biochem Physiol 2001; 128; 165-71. | ||
| In article | CrossRef | ||
| [43] | Al-Tonsi AA, Abdel-Gayoum AA, Saad M. The secondary dyslipidemia and deranged serum phosphate concentration in thyroid disorders. Exp Mol Pathol 2004; 76; 182-7. | ||
| In article | CrossRef | ||
| [44] | Sheridan MA, His Kao Y. Regulation of metamorphosis associated changes in the lipid metabolism of selected vertebrates. Amer Zoolo 1998; 38; 350-68. | ||
| In article | |||
| [45] | Morris M, Bostom A, Jacques P, Selhub J, Rosenberg I. Hyperhomocysteinemia and hypercholesterolemia associated with hypothyroidism in the third US National Health and Nutrition Examination Survey. Atherosclerosis 2001; 155; 195-200. | ||
| In article | CrossRef | ||
| [46] | Karmin O, Lynn EG, Chung YH, Siow YL, Man RY, Choy PC. Homocysteine stimulates the production and secretion of cholesterol in hepatic cells. Biochim Biophys Acta 1998; 1393; 317-24. | ||
| In article | CrossRef | ||
| [47] | Layden TJ, Boyer JL. The effect of thyroid hormone on bile salt-independent bile flow and Na+, K+-ATPase activity in liver plasma membranes enriched in bile canaliculi. J Clin Invest 1976; 57; 1009-18. | ||
| In article | CrossRef | ||
| [48] | Arora S, Chawla R, Tayal D, Gupta V, Sohi J, Mallika V. Biochemical markers of liver and kidney function are influenced by thyroid function a case-controlled follow up study in indian hypothyroid subjects. Indian J Clinic Biochem 2009; 24 (4); 370-4. | ||
| In article | CrossRef | ||
| [49] | Messarah M, Boulakoud MS, Boumendjel A, El Feki A. The impact of thyroid activity variations on some oxidizing-stress parameters in rats. C R Biol 2007; 330; 107-12. | ||
| In article | CrossRef | ||
| [50] | Yilmaz S, Ozan S, Benzer F, Canatan H. Oxidative damage an antioxidant enzyme activities in experimental hypothyroidism. Cell Biochem Funct 2003; 21; 325-30. | ||
| In article | CrossRef | ||
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