Role of complement in the pathogenesis of postpartum thyroiditis: relationship between complement activation and disease presentation and progression

1995 ◽  
Vol 133 (2) ◽  
pp. 210-215 ◽  
Author(s):  
Arthur B Parkes ◽  
Sakinah Othman ◽  
Reginald Hall ◽  
Rhys John ◽  
John H Lazarus
Keyword(s):  
Complement Activation ◽  
Thyroid Dysfunction ◽  
Clinical Syndrome ◽  
Complement C3 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Thyroid Peroxidase ◽  
Free Triiodothyronine ◽  
Postpartum Thyroiditis

Parkes AB, Othman S, Hall R, John R, Lazarus JH, Role of complement in the pathogenesis of postpartum thyroiditis: relationship between complement activation and disease presentation and progression. Eur J Endocrinol 1995;133:210–5. ISSN 0804–4643 The aim of this study was to assess whether the presentation and progression of autoimmune postpartum thyroiditis (PPT) was related to the degree of thyroid peroxidase autoantibody (TPO-ab)-mediated activation of the complement cascade. One hundred and forty-eight thyroid autoantibodypositive women have been followed during their postpartum year. Seventy-five women remained euthyroid during this time whilst the remaining 73 showed one or more episodes of thyroid dysfunction. Fourteen women showed hyperthyroid PPT, 23 showed a biphasic PPT and the remaining 36 showed hypothyroid PPT. Hyperthyroid PPT was always transient but 29 of the 59 women with hypothyroidism remained hypothyroid or still required thyroxine replacement therapy at the conclusion of the study. Thyroid autoantibodies were measured by enzyme-linked immunosorbent assay (ELISA), free triiodothyronine and free thyroxine by the Amerlex M methods and thyrotrophin by the Amerlite TSH (monoclonal) assay. Complement component C3b, immobilized as a result of classical complement pathway activation in the presence of TPO/TPO-ab complexes in vitro, was measured by ELISA. Bioactive TPO-ab were calculated as the product of the C3 index and TPO-ab level. Basal levels of complement C3 activation were seen in the euthyroid TPO-ab-positive women (C3 index 0.06 at delivery rising to 0.36 at 12 months postpartum; bioactive TPO-ab activity 0.4kIU/l at delivery rising to 10.4kIU/l at 12 months' postpartum (N = 75). These parameters were elevated progressively as the severity of the clinical syndrome increased. In 14 hyperthyroid PPT women the C3 index was 0.47 at 8 months' postpartum (bioactive TPO-ab activity=20kIU/l; p vs euthyroid group, NS). In 23 biphasic PPT women the C3 index had risen to 0.65 by 7 months' postpartum (p < 0.005 vs euthyroid group), with bioactive TPO-ab activity 81kIU/l (p < 0.005), and in 36 women with hypothyroid PPT the C3 index was 0.7 by 6 months' postpartum (p < 0.005), with bioactive TPO-ab activity 76kIU/l (p < 0.005). In women with persistent PPT the C3 index had risen to 0.76 by 5 months' postpartum, with bioactive TPO-ab activity 116kIU/l; both parameters were statistically higher in the persistent group than in the remaining 44 cases where the C3 index was 0.56, with bioactive TPO-ab activity 33 kIU/l (p < 0.005 vs euthyroid; p < 0.05 vs transient). This study of the role of complement in the pathogenesis of PPT shows that the severity and duration of the thyroid dysfunction correlates with the degree of complement activation by TPO-ab measured in vitro. AB Parkes, Autoimmunology Research Unit, Section of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Wales College of Medicine, Heath Park, Cardiff CF4 4XN, UK

scholarly journals Complement C1r serine protease contributes to kidney fibrosis

2019 ◽  
Vol 317 (5) ◽  
pp. F1293-F1304 ◽  
Author(s):  
Sandhya Xavier ◽  
Ranjit K. Sahu ◽  
Sai Vineela Bontha ◽  
Valeria Mas ◽  
Ronald P. Taylor ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Complement Activation ◽  
Kidney Tissue ◽  
Growth Factor Receptor ◽  
Tubulointerstitial Fibrosis ◽  
Complement C3 ◽  
Cellular Mechanisms ◽  
Kidney Fibrosis ◽  
Expression Of Genes

We have previously reported that complement activation precedes the development of kidney fibrosis; however, little is known about the cellular mechanisms involved in this transition. We hypothesized that increased expression of C1 complex protease C1r, the initiator of complement activation, contributes to tubulointerstitial fibrosis and tested this idea in mice with global deletion of C1r. Although expression of C1r in untreated wild-type (WT) mice was higher in the liver compared with kidney tissue, administration of folic acid (FA) led to upregulation of C1r mRNA and protein levels only in kidney tissue. Immunohistochemistry and in situ hybridization experiments localized increased expression of C1r and C1s proteases to renal tubular epithelial cells. C1r-null mice had reduced acute tubular injury and inflammation measured 2 days after FA administration compared with WT mice. C1r deletion reduced expression of C1s, C3 fragment formation, and organ fibrosis measured 14 days after FA administration. Differential gene expression performed in kidney tissue demonstrated that C1r-null mice had reduced expression of genes associated with the acute phase response, complement, proliferation of connective tissue cells (e.g., platelet-derived growth factor receptor-β), and reduced expression of genes associated with inflammation compared with FA-treated WT mice. In vitro experiments in renal epithelial cells demonstrated that C1s expression is dependent on increased C1r expression and that interferon-γ induces the expression of these two proteases. We conclude that increased expression of C1 complex proteases is associated with increased tissue inflammation and complement C3 formation and represents an important pathogenic mechanism leading to FA-mediated tubulointerstitial fibrosis.

scholarly journals Potential Role of the Chemokine Macrophage Inflammatory Protein 1α in Human and Experimental Schistosomiasis

2005 ◽  
Vol 73 (4) ◽  
pp. 2515-2523 ◽  
Author(s):  
Adriano L. S. Souza ◽  
Ester Roffê ◽  
Vanessa Pinho ◽  
Danielle G. Souza ◽  
Adriana F. Silva ◽  
...  
Keyword(s):  
Potential Role ◽  
Severe Disease ◽  
Experimental Studies ◽  
Interleukin 4 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Inflammatory Protein ◽  
Macrophage Inflammatory Protein ◽  
Deficient Mice

ABSTRACT In human schistosomiasis, the concentrations of the chemokine macrophage inflammatory protein 1α (MIP-1α/CCL3) is greater in the plasma of patients with clinical hepatosplenic disease. The objective of the present study was to confirm the ability of CCL3 to detect severe disease in patients classified by ultrasonography (US) and to evaluate the potential role of CCL3 in Schistosoma mansoni-infected mice. CCL3 was measured by enzyme-linked immunosorbent assay in the plasma of S. mansoni-infected patients. CCL3-deficient mice were infected with 25 cercariae, and various inflammatory and infectious indices were evaluated. The concentration of CCL3 was higher in the plasma of S. mansoni-infected than noninfected patients. Moreover, CCL3 was greater in those with US-defined hepatosplenic than with the intestinal form of the disease. In CCL3-deficient mice, the size of the granuloma and the liver eosinophil peroxidase activity and collagen content were diminished compared to wild-type mice. In CCL3-deficient mice, the worm burden after 14 weeks of infection, but not after 9 weeks, was consistently smaller. The in vitro response of mesenteric lymph node cells to antigen stimulation was characterized by lower levels of interleukin-4 (IL-4) and IL-10. CCL3 is a marker of disease severity in infected humans, and experimental studies in mice suggest that CCL3 may be a causative factor in the development of severe schistosomiasis.

scholarly journals The Role of Alpha-Lipoic Acid in the Pathomechanism of Acute Ischemic Stroke

2018 ◽  
Vol 48 (1) ◽  
pp. 42-53 ◽  
Author(s):  
Qingqing Wang ◽  
Chengmei Lv ◽  
Yongxin Sun ◽  
Xu Han ◽  
Shan Wang ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Lipoic Acid ◽  
Nuclear Translocation ◽  
Infarct Volume ◽  
Neurological Deficits ◽  
Experimental Stroke ◽  
Enzyme Linked Immunosorbent Assay ◽  
M2 Phenotype

Background/Aims: Ischemic stroke results in increased cerebral infarction, neurological deficits and neuroinflammation. The underlying mechanisms involving the anti-inflammatory and neuroprotective properties of α-Lipoic acid (α-LA) remain poorly understood. Herein, we investigated the potential role of α-LA in a middle cerebral artery occlusion (MCAO) rat model and an in vitro lipopolysaccharide (LPS)-induced microglia inflammation model. Methods: In the in vivo study, infarct volume was examined by TTC staining and Garcia score was used to evaluate neurologic recovery. The cytokines were evaluated by enzyme-linked immunosorbent assay, and protein expression of microglia phenotype and NF-κB were measured using western blot. In the in vitro study, the expressions of microglia M1/M2 phenotype were evaluated using qRT-PCR, and immunofluorescence staining was used to assess the nuclear translocation of NF-κB. Results: Both 20 mg/kg and 40 mg/kg of α-LA alleviated infarct size, brain edema, and neurological deficits. Furthermore, α-LA induced the polarization of microglia to the M2 phenotype, modulated the expression of IL-1β, IL-6, TNF-α and IL-10, and attenuated the activation of NF-κB after MCAO. α-LA inhibited the expression of M1 markers, increased activation of the M2 markers, and suppressed the nuclear translocation of NF-κB in LPS-stimulated BV2 microglia. Conclusions: α-LA improved neurological outcome in experimental stroke via modulating microglia M1/M2 polarization. The potential mechanism of α-LA might be mediated by inhibition of NF-κB activation via regulating phosphorylation and nuclear translocation of p65.

Single-chain antibody fragments derived from a human synthetic phage-display library bind thrombospondin and inhibit sickle cell adhesion

Blood ◽  
2003 ◽  
Vol 102 (2) ◽  
pp. 718-724 ◽  
Author(s):  
Nicholas A. Watkins ◽  
Lily M. Du ◽  
J. Paul Scott ◽  
Willem H. Ouwehand ◽  
Cheryl A. Hillery
Keyword(s):  
Sickle Cell ◽  
Matrix Protein ◽  
Binding Domain ◽  
Extracellular Matrix Protein ◽  
Enzyme Linked Immunosorbent Assay ◽  
Adhesion Assay ◽  
Single Chain ◽  
Cell Binding

AbstractThe enhanced adhesion of sickle red blood cells (RBCs) to the vascular endothelium and subendothelial matrix likely plays a significant role in the pathogenesis of vaso-occlusion in sickle cell disease. Sickle RBCs have enhanced adhesion to the plasma and extracellular matrix protein thrombospondin-1 (TSP) under conditions of flow in vitro. In this study, we sought to develop antibodies that bind TSP from a highly diverse library of human single-chain Fv fragments (scFvs) displayed on filamentous phage. Following 3 rounds of phage selection of increasing stringency 6 unique scFvs that bound purified TSP by enzyme-linked immunosorbent assay were isolated. Using an in vitro flow adhesion assay, 3 of the 6 isolated scFvs inhibited the adhesion of sickle RBCs to immobilized TSP by more than 40% compared with control scFvs (P &lt; .001). Furthermore, scFv TSP-A10 partially inhibited sickle RBC adhesion to activated endothelial cells (P &lt; .005). Using TSP proteolytic fragments to map the binding site, we showed that 2 of the inhibitory scFvs bound an epitope in the calcium-binding domain or proximal cell-binding domain of TSP, providing evidence for the role of these domains in the adhesion of sickle RBCs to TSP. In summary, we have isolated a panel of scFvs that specifically bind to TSP and differentially inhibit sickle RBC adhesion to surface-bound TSP under flow conditions. These scFvs will be useful reagents for investigating the role of the calcium and cell-binding domains of TSP in sickle RBC adhesion.

Serum Proteins Opsonization and Phagocytic Uptake of PEG-Modified PLGA Nanoparticles: Effect of Particle Size

2011 ◽  
Vol 393-395 ◽  
pp. 939-942 ◽  
Author(s):  
An Shu Yang ◽  
Wei Liu ◽  
Xiang Liang Yang
Keyword(s):  
Particle Size ◽  
Serum Protein ◽  
Complement Activation ◽  
Serum Proteins ◽  
Enzyme Linked Immunosorbent Assay ◽  
Spontaneous Emulsification ◽  
Protein Assay ◽  
Effect Of Particle Size ◽  
Serum Dependent

The purpose of this study is to evaluate the effect of particle size on serum protein opsonization and in vitro macrophage uptake of polyethyleneglycol modified poly (D, L-lactide-co-glycolide) nanoparticles (PEG-PLGA-NPs). PEG-PLGA-NPs were prepared by modified-spontaneous emulsification solvent diffusion (modified-SESD) method. Serum protein adsorptions to PEG-PLGA-NPs were evaluated by bicinchoninic acid (BCA) protein assay and enzyme-linked immunosorbent assay (ELISA). Complement activation was also investigated by ELISA for complement fragments iC3b. Uptake of PEG-PLGA-NPs by macrophages was measured by fluorescence spectrometer. The results showed that serum protein adsorption and complement activation were augmented for nanoparticles with a larger size below 400 nm. Phagocytosis of PEG-PLGA-NPs by murine peritoneal macrophages involved serum-independent and serum-dependent phagocytosis. Serum-independent phagocytosis decreased, while serum-dependent phagocytosis increased with the increase of particle size in the nanometer and submicrometer range. Consequently, nanoparticles with size of about 400 nm were phagocytosed more readily than either smaller or larger particles

scholarly journals Relationship between Different Psoriasis Types and Thyroid Dysfunction: A Retrospective Analysis

Scanning ◽  
2021 ◽  
Vol 2021 ◽  
pp. 1-5
Author(s):  
Juan Du ◽  
Chunyue Ma ◽  
Runnan Wang ◽  
Lanmei Lin ◽  
Luhui Gao ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Thyroid Function ◽  
Thyroid Dysfunction ◽  
Thyroid Stimulating Hormone ◽  
Thyroid Peroxidase ◽  
Thyroid Function Tests ◽  
Free Triiodothyronine ◽  
Hormone Levels ◽  
Significant Difference ◽  
Total Thyroxine

Objective. The aim of this study was to investigate the relationship between different psoriasis types and thyroid dysfunction. Methods. The data of patients diagnosed with psoriasis between January 2013 and October 2018 who underwent thyroid function tests were collected. Free triiodothyronine (FT3), free thyroxine (FT4), total triiodothyronine (TT3), total thyroxine (TT4), thyroid-stimulating hormone (TSH), thyroglobulin antibody (TGAb), and thyroid peroxidase antibody (TPOAb) were measured. The thyroid function of patients with psoriasis vulgaris, pustular psoriasis, erythrodermic psoriasis, and psoriatic arthritis was evaluated, and the differences in hormone levels and antibodies in the pituitary-thyroid axis with psoriasis type were analyzed. Results. The data of a total of 468 patients were analyzed in this study. The proportion of normal hormone levels was higher among vulgaris patients ( P < 0.001 ), while the erythrodermic patients were more likely to have decreased FT3 or FT4 but normal TSH ( P < 0.001 ). FT3 levels were lower in pustular patients ( P < 0.05 ), FT4 levels were lower in erythrodermic patients ( P < 0.05 ), and TSH levels were higher in patients with psoriatic arthritis ( P < 0.05 ). TPOAb levels were higher than normal in all patients, but there was no significant difference in the levels of TPOAb and TGAb among 4 types of the patients. Conclusion. Psoriasis is related to thyroid dysfunction, especially in patients with atypical psoriasis types. The possibility of complications should be considered in erythrodermic patients.

NO LONGTERM SEVERE THYROID DYSFUNCTION SEEN IN PATIENTS WITH PREEXISTING REDUCED SERUM TT3 CONCENTRATIONS AFTER A SINGLE LARGE DOSE OF IODINATED CONTRAST

2020 ◽  
Vol 26 (8) ◽  
pp. 840-845
Author(s):  
Si Hai-Long ◽  
Qin Qin ◽  
Liu Yuan-Yuan ◽  
Zhao Bing-Rang
Keyword(s):  
Thyroid Dysfunction ◽  
Coronary Intervention ◽  
Thyroid Stimulating Hormone ◽  
World Health ◽  
Thyroid Peroxidase ◽  
Free Triiodothyronine ◽  
Iodinated Contrast ◽  
Total Triiodothyronine ◽  
Total Thyroxine ◽  
Health Organization

Objective: After an intravenous bolus injection of 100 mL of iodinated contrast agent (370 mgI/mL), the amount of iodine atoms entering the blood is tens of thousands of times the daily dose of iodine recommended by the World Health Organization. However, the effect of iodinated contrast in patients with nonthyroidal illness, manifested as reduced serum total triiodothyronine (TT3) concentrations, is unclear. We studied the effect of iodinated contrast on thyroid function and auto-antibodies in patients with reduced TT3 after diagnosis and treatment of coronary heart disease. Methods: This was a prospective cohort study. One hundred and fifty-four stable angina pectoris patients with reduced TT3 and normal thyroid-stimulating hormone (TSH), free thyroxine (FT4), and reverse triiodothyronine (rT3) were enrolled from January, 2017, to June, 2018. All subjects had no history of thyroid dysfunction and had no recent infections, tumors, trauma, or other critical illnesses. Fourty-one patients underwent coronary angiography and 113 patients underwent coronary intervention. Results: There were 6 patients (3.9%) with hypothyroidism and 30 patients (19.5%) developed subclinical hypothyroidism (SCHypo) on the first day after surgery. There were 6 patients (3.9%) with hypothyroidism, 6 patients (3.9%) with SCHypo, and 18 patients (11.7%) with subclinical hyperthyroidism (SCHyper) at the first month postsurgery. There were 23 patients (14.9%) with SCHyper and 6 patients (3.9%) with SCHypo at the sixth month after surgery. No patient with longterm severe thyroid dysfunction occurred during follow-up. The levels of free triiodothyronine, FT4, TT3, total thyroxine, and TSH showed statistically significant changes at 1 day, and 1, 3, and 6 months postoperative ( P<.005). The level of rT3 showed no statistically significant change at 1, 3, and 6 months postoperative ( P>.05). The levels of thyroglobulin antibody and thyroid peroxidase antibody decreased at 6 months postoperative ( P<.001). Conclusion: The risk of subclinical thyroid dysfunction and transient hypothyroidism occurred with a single large dose of iodinated contrast in the diagnosis and treatment of coronary heart disease, but no longterm severe thyroid dysfunction occurred. Patients with preoperative thyroid antibody elevation were more likely to have subclinical thyroid dysfunction after surgery. Abbreviations: FT3 = free triiodothyronine; FT4 = free thyroxine; PCI = percutaneous coronary intervention; rT3 = reverse triiodothyronine; SCHyper = subclinical hyperthyroidism; SCHypo = subclinical hypothyroidism; TGAB = thyroglobulin antibody; TPOAB = thyroid peroxidase antibody; TT3 = total triiodothyronine; TT4 = total thyroxine; TSH = thyroid-stimulating hormone; WHO = World Health Organization

Complement activating ABO IgM/IgG act synergistically to cause erythrophagocytosis: implications among minor ABO incompatible platelet transfusions

2020 ◽  
Author(s):  
Priyanka Pandey ◽  
Waseem Q. Anani ◽  
Tina Pugh ◽  
Jerome L. Gottschall ◽  
Gregory A Denomme
Keyword(s):  
Complement Activation ◽  
Complement C3 ◽  
Transfusion Reaction ◽  
Single Donor ◽  
Healthy Donors ◽  
Hemolytic Transfusion Reaction ◽  
Group A ◽  
Donor Sample ◽  
Donor Plasma

Abstract Background Typically minor ABO incompatible platelet products are transfused without any incident, yet serious hemolytic transfusion reactions occur. To mitigate these events, ABO ‘low titer’ products are used for minor ABO incompatible transfusions. We sought to understand the role of IgG and complement activation by anti-A on extravascular hemolysis. Samples evaluated: i) Group O plasma from a blood donor whose apheresis platelet product resulted in an extravascular transfusion reaction, ii) Group O plasma from 12 healthy donors with matching titers that activated complement (N = 6) or not (N = 6), and iii) Group O sera from 10 patients with anti-A hemolysin activity. Monocytes from healthy donors were co-incubated with anti-A-sensitized fluorescently-labeled Group A1+ RBCs with and without fresh Group A serum, as a source of complement C3, and phagocytosis was analyzed by flow cytometry. The plasma and sera had variable direct agglutinating (IgM) and indirect (IgG) titers. Results None of 12 selected samples showed monocyte-dependent erythrophagocytosis with or without complement activation. The donor sample causing a hemolytic transfusion reaction and 2 of the 10 patient sera with hemolysin activity showed significant erythrophagocytosis (>10%) only when complement C3 was activated. The single donor plasma and two sera demonstrating significant erythrophagocytosis had high IgM (≥128) and IgG titers (>1024). The donor plasma anti-A was IgG1, while the patient sera were an IgG3 and an IgG1 plus IgG2. Conclusion High anti-A IgM/IgG titers act synergistically to cause significant monocyte erythrophagocytosis by activating complement C3, thus engaging both Fcγ- and CR1-receptors.

Human Macrophages Phagocytose Rituximab Opsonised Leukemic Cells Via CD16, CD32 and CD64 but Do Not Mediate ADCC.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2507-2507
Author(s):  
Josee Golay ◽  
Marzia Leidi ◽  
Giuseppe A. Palumbo ◽  
Martino Introna
Keyword(s):  
Complement Activation ◽  
Xenograft Model ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Therapeutic Activity ◽  
Blood Monocytes ◽  
Response Curves ◽  
Human Macrophages

Abstract Rituximab (Mabthera®) is a chimeric monoclonal IgG1 antibody with therapeutic activity in non-Hodgkin B lymphomas (B-NHL) and B-Chronic Lymphocytic Leukemia (B-CLL). We have recently obtained evidence, using a bulky lymphoma xenograft model in nude mice, that both complement and macrophages are required for the therapeutic activity of rituximab. In order to further investigate the tumor cell killing potential of macrophages and its modulation by different factors, including complement, we have set up in vitro experiments with purified macrophage populations. Human macrophages were obtained from purified peripheral blood monocytes cultured for 4 days in presence of 20% FCS and 20 ng/ml M-CSF. FACS analysis confirmed the phenotype of these cells including CD11b and FcγRs expression (CD16, CD32, CD64). Phagocytosis assays were then carried out with CLL cell as targets in presence or absence of increasing concentrations of rituximab. Phagocytosis was evaluated by counting under an inverted microscope the stained cytospin preparations. From 9.8% to 60.8% of macrophages engulfed at least one tumor target cell in a series of 24 experiments (mean 29.7%± 18.3%). Control irrelevant IgG1k monoclonal antibodies (anti-erbB2 trastuzumab and anti-EGFR cetuximab) did not mediate phagocytosis, and rituximab did not lead to ingestion of CD20 negative cells, demonstrating the specificity of the assay. Phagocytosis was already maximal at around 0.1 μg/ml rituximab concentration. In contrast complement activation required Mab concentration of at least 1 μg/ml. Thus phagocytosis, like ADCC, is active at about 10 fold lower MAb concentrations than complement triggering. Levels of CD20 expression on targets did not significantly affect phagocytosis. The role of different FcγRs was also investigated by addition 5 μg/ml blocking antibodies to CD16, CD32 and CD64. All 3 blocking Mabs reduced significantly phagocytosis (by 45%, 42% and 40% respectively with respect to control). Inhibition increased to 64% in presence of all 3 antibodies. Since previous data had suggested a role of the Val/Phe polymorphism at position 158 of CD16A in the clinical response of lymphoma patients to rituximab as well as in NK-mediated ADCC, we investigated whether this polymorphism also affected phagocytosis. No significant differences in dose response curves were observed using macrophages from either Val-Val or Phe-Phe homozygotes. Perhaps surprisingly, concomitant complement activation induced by addition of human serum did not increase phagocytosis. Whether human macrophages can also mediate antibody dependent cellular cytotoxicity (ADCC) was also studied. CLL or BJAB cells were labeled with Calcein-AM and ADCC measured as released fluorescence after 4 hours at 37°C. Macrophages were unable to mediate ADCC in presence of rituximab even following treatment with IFNγ (100 U/ml) for 48 hours. We conclude that macrophages efficiently mediate phagocytosis but not ADCC in presence of low concentrations of rituximab.

scholarly journals Dronedarone and Amiodarone Induce Dyslipidemia and Thyroid Dysfunction in Rats

2016 ◽  
Vol 38 (6) ◽  
pp. 2311-2322 ◽  
Author(s):  
Li-Qin Jiang ◽  
Shan-Jiang Chen ◽  
Jian-Jiang Xu ◽  
Zhang Ran ◽  
Wang Ying ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Mrna Expression ◽  
Thyroid Dysfunction ◽  
Early Stage ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Thyroid Peroxidase ◽  
Sprague Dawley ◽  
Free Triiodothyronine

Background/Aims: Amiodarone, a thyroid hormone-like molecule, can induce dyslipidemia and thyroid dysfunction. However, the effects of dronedarone on lipid metabolism and of both dronedarone and amiodarone on thyroid function and lipid metabolism remain unknown. Methods: Fifty male Sprague-Dawley rats were randomly divided into 5 groups (10 in each group): normal control (NC), amiodarone-treated (AMT), dronedarone-treated (DRT), rats treated with amiodarone combined with polyene phosphatidylcholine (AC), and rats treated with dronedarone combined with polyene phosphatidylcholine (DC). Rats were given amiodarone (120 mg/kg/d), dronedarone (120 mg/kg/d), and polyene phosphatidylcholine (200 mg/kg/d) for 13 weeks. At the end of weeks 4, 8, 12, and 13, plasma-free triiodothyronine (FT3), free thyroxine (FT4), triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c) were determined. At the end of this protocol, rats were sacrificed and the thyroid glands were isolated, weighed, and examined histopathologically. The protein expression of Bcl-2 was measured by immunochemical staining. The mRNA expression of thyroglobulin (Tg), type-1 deiodinase (D1), and thyroid peroxidase (TPO) were detected by polymerase chain reaction (PCR). Results: Compared with the NC group, FT3 and FT4 levels in the DRT and DC groups significantly increased at week 4 but declined thereafter. The AMT and AC groups had lower FT3 levels but comparable FT4 levels. The levels of TG, LDL-c, and HDL-c in the NC group were lower than those in the other groups whereas the LDL-c/HDL-c ratio was lowest in the AMT group. Bcl-2 expression significantly increased in the DRT group. The mRNA expression of Tg increased whereas the mRNA expression of D1 decreased. Dronedarone induced hyperthyroidism at the early stage and hypothyroidism at the late stage whereas amiodarone only caused hypothyroidism. Conclusion: Both dronedarone and amiodarone can induce dyslipidemia and increase the levels of TC, LDL-c, and HDL-c, and these effects may be associated with thyroid dysfunction.

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