Jan Stepniak

Potassium iodide, but not potassium iodate, as a potential protective agent against oxidative damage to membrane lipids in porcine thyroid

BackgroundFenton reaction (Fe2++H2O2→Fe3++•OH+OH−) is of special significance in the thyroid gland, as both its substrates, i.e. H2O2 and Fe2+, are required for thyroid hormone synthesis. Also iodine, an essential element supplied by the diet, is indispensable for thyroid hormone synthesis. It is well known that iodine affects red-ox balance. One of the most frequently examined oxidative processes is lipid peroxidation (LPO), which results from oxidative damage to membrane lipids. Fenton reaction is used to experimentally induce lipid peroxidation. The aim of the study was to evaluate effects of iodine, used as potassium iodide (KI) or potassium iodate (KIO3), on lipid peroxidation in porcine thyroid homogenates under basal conditions and in the presence of Fenton reaction substrates.MethodsPorcine thyroid homogenates were incubated in the presence of either KI (0.00005 – 500 mM) or KIO3 (0.00005 – 200 mM), without or with addition of FeSO4 (30 μM) + H2O2 (0.5 mM). Concentration of malondialdehyde + 4-hydroxyalkenals (MDA + 4-HDA) was measured spectrophotometrically, as an index of lipid peroxidation.ResultsPotassium iodide, only when used in the highest concentrations (≥50 mM), increased lipid peroxidation in concentration-dependent manner. In the middle range of concentrations (5.0; 10; 25; 50 and 100 mM) KI reduced Fenton reaction-induced lipid peroxidation, with the strongest protective effect observed for the concentration of 25 mM. Potassium iodate increased lipid peroxidation in concentrations ≥2.5 mM. The damaging effect of KIO3 increased gradually from the concentration of 2.5 mM to 10 mM. The strongest damaging effect was observed at the KIO3 concentration of 10 mM, corresponding to physiological iodine concentration in the thyroid. Potassium iodate in concentrations of 5–200 mM enhanced Fenton reaction-induced lipid peroxidation with the strongest damaging effect found again for the concentration of 10 mM.ConclusionsPotassium iodide, used in doses generally recommended in iodide prophylaxis, may prevent oxidative damage to membrane lipids in this gland. Toxic effects of iodide overload may result from its prooxidative action. Potassium iodate does not possess any direct beneficial effects on oxidative damage to membrane lipids in the thyroid, which constitutes an additional argument against its utility in iodine prophylaxis.

High level of oxidized nucleosides in thyroid mitochondrial DNA; damaging effects of Fenton reaction substrates

BackgroundThe mitochondrial DNA (mtDNA) lies in close proximity to the free radical-producing electron transport chain, thus, it is highly prone to oxidative damage. Oxyphilic type of follicular thyroid carcinoma consists of cells filled – almost exclusively – with aberrant mitochondria. In turn, bivalent iron (Fe2+) and hydrogen peroxide (H2O2) are indispensable for thyroid hormone synthesis, therefore being available in physiological conditions presumably at high concentrations. They participate in Fenton reaction (Fe2++H2O2→Fe3++·OH + OH-), resulting in the formation of the most harmful free radical – hydroxyl radical (·OH). The same substrates may be used to experimentally induce oxidative damage to macromolecules. The aim of the study was to evaluate the background level of oxidative damage to mtDNA and the damaging effects of Fenton reaction substrates.MethodsThyroid mtDNA was incubated in the presence of either H2O2 [100, 10, 1.0, 0.5, 0.1, 0.001, 0.00001 mM] or FeSO4 (Fe2+) [300, 150, 30, 15, 3.0, 1.5 μM], or in the presence of those two factors used together, namely, in the presence of Fe2+ [30 μM] plus H2O2 [100, 10, 1.0, 0.5, 0.1, 0.001, 0.00001 mM], or in the presence of H2O2 [0.5 mM] plus Fe2+ [300, 150, 30, 15, 3.0, 1.5 μM]. 8-oxo-7,8-dihydro-2’-deoxyguanosine (8-oxodG) concentration, as the index of DNA damage, was measured by HPLC.ResultsBoth Fenton reaction substrates, used separately, increased 8-oxodG level for the highest H2O2 concentration of 100 mM and in Fe2+ concentration-dependent manner [300, 150, and 30 μM].When Fe2+ and H2O2 were applied together, Fe2+ enhanced H2O2 damaging effect to a higher degree than did H2O2 on Fe2+ effect.ConclusionsThe level of oxidized nucleosides in thyroid mtDNA is relatively high, when compared to nuclear DNA. Both substrates of Fenton reaction, i.e. ferrous ion and hydrogen peroxide, increase oxidative damage to mtDNA, with stronger damaging effect exerted by iron. High level of oxidative damage to mtDNA suggests its possible contribution to malignant transformation of thyroid oncocytic cells, which are known to be especially abundant in mitochondria, the latter characterized by molecular and enzymatic abnormalities.

17β-estradiol prevents experimentally-induced oxidative damage to membrane lipids and nuclear DNA in porcine ovary

Abstract Estrogens, with their principle representative 17β-estradiol, contribute to the redox state of cells showing both pro- and antioxidative properties. In the ovary, being the main source of estrogens, maintaining balance between the production and detoxification of ROS is crucial. Whereas ovary estrogen concentration is difficult to estimate, its circulating concentration in women may reach the nanomolar level. The aim of the study was to evaluate the effects of 17β-estradiol on oxidative damage to membrane lipids (lipid peroxidation, LPO) and to nuclear DNA in the porcine ovary under basal conditions and in the presence of Fenton reaction (Fe2++H2O2→Fe3++•OH + OH−) substrates. Ovary homogenates and DNA were incubated in the presence of 17β-estradiol (1 mM–1 pM), without/with FeSO4 (30 μM) + H2O2 (0.5 mM). Malondialdehyde + 4-hydroxyalkenals (MDA + 4-HDA) concentration (LPO index) was measured spectrophotometrically. The concentration of 8-oxo-7,8-dihydro-2’-deoxyguanosine (8-oxodG) (DNA damage index) was measured by HPLC. We observed that 17β-estradiol did not alter the basal level of oxidative damage, but reduced Fe2++H2O2-induced oxidative damage to membrane lipids when ≥10 nM and to DNA at concentrations ≥1 nM. In the ovary at near physiological concentration, 17β-estradiol prevents experimentally induced oxidative damage. This suggests that under physiological conditions this hormone may contribute to protecting the ovary against oxidative damage.

TSH ≥2.5 mIU/l is Associated with the Increased Oxidative Damage to Membrane Lipids in Women of Childbearing Age with Normal Thyroid Tests

According to current recommendations, a TSH value of <2.5 mIU/l should be maintained during preconception and pregnancy. The same recommendation, however, does not relate to all women of childbearing age. The aim of the study was to evaluate relationship between lipid peroxidation (LPO; index of oxidative damage to membrane lipids) and thyroid tests and other parameters, which may be affected by thyroid dysfunction, in euthyroid women of childbearing age. Ninety nine female inpatients with normal thyroid tests (TSH 0.27-4.2 mIU/l), aged 18-48 years, were prospectively enrolled. Blood concentrations of malondialdehyde+4-hydroxyalkenals (LPO index) were measured spectrophotometrically. Thyroid tests (TSH, FT4, FT3), thyroid antibodies and other laboratory parameters [cholesterol, HDL cholesterol (HDLC), LDL cholesterol, HDLC/cholesterol ratio, triglycerides, glucose, CRP, iron] were measured with standard methods. Blood LPO level was higher in women with TSH≥2.5 mIU/l than in women with TSH<2.5 mIU/l. Positive correlation was found between TSH concentration and LPO level (r=0.210, p=0.037). In the univariate regression analysis, blood LPO level did constitute the only independent factor associated with TSH≥2.5 mIU/l. Abnormal HDLC/cholesterol ratio occurred more frequently in subjects with TSH≥2.5 mIU/l. Additionally, LPO level correlated positively with triglyceride concentration (r=0.340, p=0.001), whereas it correlated negatively with HDLC concentration (r=-0.335, p=0.001) and with HDL/cholesterol ratio (r=-0.331, p=0.001). In conclusion, in women of childbearing age with normal thyroid tests, TSH≥2.5 mIU/l is associated with higher oxidative damage to membrane lipids and less favorable lipid profile, which supports our standpoint that TSH of less than 2.5 mIU/l should be maintained in all women of childbearing age.

Relationship between urine lipid peroxidation, anthropometric parameters and parameters associated with goitre formation in school-age children

Introduction Oxidative stress has been implicated in the normal ageing process and the pathogenesis of several diseases, including goitre. The aim of the study was to evaluate the relationship between urine lipid peroxidation (LPO) and anthropometric parameters as well as the parameters associated with goitre formation in children. Material and methods The subjects included 172 healthy children (93 girls and 79 boys) aged 8–15, divided into 4 age groups – group I (8–9 years), group II (10–11 years), group III (12–13 years) and group IV (14–15 years) – and into 2 groups based on the BSA: the BSA-1 group (≤ 0.55 m2) and the BSA-2 group (> 0.55 m2). Results The value of LPO was the highest in group I but the difference between the groups was not statistically significant (p = 0.074). In the BSA-1 group, the LPO was higher than in the BSA-2 group (12.75 ±6.90 nmol/ml and 10.79 ±4.86 nmol/ml, respectively; p = 0.023). We found a weak, negative linear correlation between LPO and age (r = –0.216; p < 0.005), body mass (r = –0.153; p < 0.05), height (r = –0.152; p < 0.05) and BSA (r = –0.151; p < 0.05). Conclusions Anthropometric parameters of school-age children independently of age are negatively associated with oxidative damage to membrane lipids, whereas factors promoting goitrogenesis do not contribute to this process.