4-hydroxy-2-nonenal and Hyperthyroidism

Metabolic dysfunctions might play a crucial role in the pathophysiology of thyroid dysfunctions. This study aimed to investigate the impact of a controlled diet (normal versus high fat feeding) on hypothyroid and hyperthyroid Sprague Dawley rats. Female Sprague Dawley rats (n = 66) were grouped into normal diet (n = 30) and high-fat diet (n = 36) groups and subdivided into controls, hypothyroid and hyperthyroid groups, induced through propylthiouracil or triiodothyronine (T3) treatment, respectively. After 12 weeks of treatment metabolic parameters, such as oxidized LDL (oxLDL), malondialdehyde (MDA), 4-hydroxynonenal (HNE), the lipid profile, body weight and food intake parameters were analyzed. Successfully induced thyroid dysfunctions were shown by T3 levels, both under normal and high fat diet. Thyroid dysfunctions were accompanied by changes in calorie intake and body weight as well as in the lipid profile. In detail, hypothyroid rats showed significantly decreased oxLDL levels, whereas hyperthyroid rats showed significantly increased oxLDL levels. These effects were seen under high fat diet and were less pronounced with normal feeding. Taken together, we showed for the first time in female SD rats that only hyper-, but not hypothyroidism, is associated with high atherogenic oxidized LDL irrespective of normal or high-fat diet in Sprague Dawley rats.

Topics: Aldehydes; Animals; Body Weight; Diet, High-Fat; Female; Hyperthyroidism; Hypothyroidism; Lipid Metabolism; Lipids; Lipoproteins, LDL; Malondialdehyde; Rats; Rats, Sprague-Dawley; Thyroid Gland

The lipid peroxidation product 4-hydroxynonenal (HNE) is a biomarker of oxidative stress which is essentially involved in the pathophysiology of many diseases. The analysis of HNE is challenging because this aldehyde is extremely reactive and thus unstable. Hence, we adopted a gas chromatography-mass spectrometry (GC-MS) method based on derivatization of HNE with pentafluorobenzyl-hydroxylamine-HCl followed by trimethylsilylation to trimethylsilyl ethers. Ions representative for a negative ion chemical ionization mode were recorded at m/z = 152 for HNE and at m/z = 162 for the deuterated analogon (HNE-d11) as internal standard. This excellent stable and precise GC-MS method was carefully validated for HNE, and showed good linearity (r(2) = 0.998), and high specificity and sensitivity. Within-day precisions were 4.4-6.1% and between-day precisions were 5.2-10.2%. Accuracies were between 99% and 104% for the whole calibration range (2.5-250 nmol/L) of HNE. To examine the versatility of this modified GC-MS method, we analyzed HNE in ethylenediaminetetraacetic acid (EDTA) plasma in a well-defined collective of migraine patients; recently published. The results underline our former observations that women with migraine are afflicted with increased levels of HNE. Patients with thyroidal dysfunction showed no significant HNE alterations. This was confirmed by normal HNE EDTA plasma levels in hyper- und hypothyroid Sprague-Dawley rats. Taken together, the GC-MS method presented herein is of excellent quality to record oxidative stress-related bioactive HNE levels. This is important for a reorientation of oxidative stress analytics in other human diseases first of atherosclerosis and cancer.

Topics: Adult; Aldehydes; Animals; Biomarkers; Case-Control Studies; Female; Gas Chromatography-Mass Spectrometry; Humans; Hydroxylamines; Hyperthyroidism; Hypothyroidism; Lipid Peroxidation; Migraine Disorders; Rats; Rats, Sprague-Dawley; Sensitivity and Specificity; Trimethylsilyl Compounds

The aim of this study was to evaluate the influence of hyperthyroidism on lipid peroxidation and oxidative modification of low density lipoprotein (LDL). Twenty patients with hyperthyroidism due to Graves' disease or toxic multinodular goitre and 17 healthy subjects as the control group were investigated. Lipid peroxidation was measured by the serum level of malondialdehyde and 4-hydroxynonenal (MDA+4-HNE) whereas the oxidative modification of LDL was determined by measuring the serum levels of antibodies against oxidized LDL (anti-oxLDL). Ratios, which were evaluated as proportions of lipid peroxidation products level or anti-oxLDL level to the LDL-cholesterol level (LDL-C) were also determined: MDA+4-HNE/LDL-C and anti-oxLDL/LDL-C. The patients with hyperthyroidism displayed a significant elevation of the MDA+4-HNE/LDL-C ratio. The level of anti-oxLDL and anti-oxLD/LDL-C ratio were positively correlated with FT4 level and inversely correlated with HDL-cholesterol. These data suggest that the intensification of lipid peroxidation and oxidative modification of plasma lipoprotein is affected by changes in the level of thyroid hormones.

Topics: Adult; Aged; Aged, 80 and over; Aldehydes; Antibodies; Case-Control Studies; Cholesterol, LDL; Humans; Hyperthyroidism; Lipid Peroxidation; Lipoproteins, LDL; Male; Malondialdehyde; Middle Aged