Total Antioxidant Capacity: Biochemical Aspects and Clinical Significance.

Despite the physiological role of oxidant molecules, oxidative stress (OS) could underlie several human diseases. When the levels of antioxidants are too low or too high, OS occurs, leading to damage at the molecular, tissue and cellular levels. Therefore, antioxidant compounds could represent a way to modulate OS and/or to maintain proper redox balance. This review provides an overview of the methods available to assess total antioxidant capacity (TAC) in biological systems to elucidate the correct terminology and the pathophysiological roles. The clinical context is fundamental to obtain a correct interpretation of TAC. Hence, we discuss metabolic syndrome and infertility, two clinical conditions that involve OS, including the potential prognostic role of TAC evaluation in monitoring antioxidant supplementation. This approach would provide more personalised and precise therapy.

Insulin-sensitizing effect and antioxidant action of alpha lipoic acid in oligomenorrheic women with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a low-grade inflammatory disease characterized by anovulation and hyperandrogenism, associated with insulin-resistance. The aim of our study was to investigate the effects of a treatment with alpha-lipoic acid on clinical, endocrine, and metabolic features of women affected by PCOS. METHODS: In this pilot cohort study, 60 women (30 hyperinsulinemic and 30 normoinsulinemic patients; age 15-34 years) were enrolled and clinical, hormonal, and metabolic parameters were evaluated before and after a six-months treatment with alpha-lipoic acid 800 mg/daily. Investigations were performed during the early follicular phase of the menstrual cycles (spontaneous or progestin-induced cycles): after fasting overnight for 10-12 h, blood samples were collected for hormonal and metabolic assays and oral glucose tolerance test and pelvic ultrasound were performed. Total Antioxidant Capacity was expressed as LAG time. RESULTS: The treatment was able to increase the number of menstrual cycles during the 6 months considered in all patients and to reduce BMI in the normoinsulinemic population. In hyperinsulinemic patients we observed a statistically significant reduction in AUC-I as well as an increase of total antioxidant capacity. CONCLUSIONS: The relevant results in restoring menstrual cyclicity in both groups, in addition to the antioxidant effect, confirm that hyperinsulinemia influences only the metabolic response to the treatment, without predict the ovarian function. Even if alpha-lipoic acid mechanisms of action is not clear and further studies are needed to confirm these results, it could be considered a valid therapeutic alternative to traditional drugs, without side effects as reported.

Inflammation and Oxidative Stress in Seminal Plasma: Search for Biomarkers in Diagnostic Approach to Male Infertility.

Oxidative and inflammatory damage underlie several conditions related to male infertility, including varicocele. Free light chains of immunoglobulins (FLCs) are considered markers of low-grade inflammation in numerous diseases. Coenzyme Q10 (CoQ10), a lipidic antioxidant and anti-inflammatory compound, is involved in spermatozoa energy metabolism and motility. We aimed to evaluate FLCs' seminal levels in patients with varicocele in comparison to control subjects and to correlate them with CoQ10 and Total Antioxidant Capacity (TAC) in human semen. Sixty-five patients were enrolled. Semen analysis was performed; patients were divided into three groups: controls, 12 normozoospermic patients, aged 34 (33-41) years; varicocele (VAR), 29 patients, aged 33 (26-37) years; and idiopathic, 24 oligo-, astheno- and oligoasthenozoospermic patients aged 37 (33.5-40.5) years. FLCs (κ and λ) were assayed by turbidimetric method; CoQ10 by HPLC; TAC by spectrophotometric method. λ FLCs showed a trend toward higher levels in VAR vs. controls and the idiopathic group. VAR showed a trend toward lower κ FLCs levels vs. the other two groups. When comparing κ/λ ratio, VAR showed significantly lower levels vs. controls and idiopathic. Moreover, CoQ10 seminal levels showed higher levels in VAR and idiopathic compared to controls. Data reported here confirm lower levels of κ/λ ratio in VAR and suggest a possible application in personalized medicine as clinical biomarkers for male infertility.

Can plasma antioxidants prevent DNA damage in oxidative stress condition induced by growth hormone deficiency? A pilot study.

Adult growth hormone deficiency (GHD), a condition characterized by increased oxidative stress, is related to augmented cardiovascular, metabolic and oncological risk. A case-control observational study has been performed to evaluate DNA oxidative damage analysing the production of thymidine-glycol in lymphocytes and its correlation with plasma antioxidant levels, evaluated as Total Antioxidant Capacity (TAC). GHD was diagnosed using GHRH 50µg iv+arginine 0,5 g/Kg test, with peak GH response <9 µg/L when BMI was <30 kg/m2 or <4 µg/L when BMI was >30 kg/m2. Three groups were identified: total GHD (n = 16), partial GHD (n = 11), and controls (n = 12). Thymidine-glycol, TAC and IGF-1 have been determined respectively in lymphocytes, plasma and serum samples. When considering thymidine-glycol, we found a significant difference between total vs partial GHD and controls. Unexpectedly thymidine-glycol was lower in total GHD, also accompanied with a significant increase in plasmatic TAC. Our results showed that in adult GHD condition, the production of antioxidant species, in response to increased oxidative stress, could exert a protective effect on thymidine-glycol formation, and consequently on DNA intracellular damages. This pilot study could be inserted in the complex scenario of oxidative damage of GHD, a subtle, yet poorly defined condition, worthy of further insights.

Corrigendum to "Anabolic Hormone Deficiencies in Heart Failure with Reduced or Preserved Ejection Fraction and Correlation with Plasma Total Antioxidant Capacity".

[This corrects the article DOI: 10.1155/2020/5798146.].

Oxidative stress and anabolic hormones in back pain: Current concept and preliminary analysis in male cohort.

Back Pain (BP) is a common medical problem; anabolic hormones, through the modulation of oxidative stress (OS), could influence fracture risk. We evaluated the prevalence of anabolic hormonal deficiencies and their relationship with OS in males with BP, associated or not to nontraumatic fractures. 49 males with BP, from 36 to 80 years, were divided in two groups according to radiological evidence of nontraumatic fractures; group A (n=25): non-fractured; group B (n=24): fractured. A different prevalence of hormonal deficits was observed: 24% of hypotestosteronemia in A, 0% in B; 16% of GHD in A, 29% in B; Total Antioxidant Capacity (TAC) showed a trend toward higher levels in B. In A, despite lower TAC, a significant inverse correlation was present between TAC and IGF-1. A greater prevalence of GHD in patients with vertebral fractures was seen and, in a subgroup, OS could mediate the deleterious effects of hyposecretory GH state.

Evaluation of oxidative stress effects on different macromolecules in adult growth hormone deficiency.

Adult growth hormone deficiency (GHD) is being increasingly recognized to cause premature mortality exacerbated by oxidative stress. A case-control observational study has been performed with the primary objective of evaluating new parameters of oxidative stress and macromolecular damage in adult GHD subjects: serum nitrotryptophan; Total Antioxidant Capacity expressed as LAG time; urinary hexanoil-lysine; urinary dityrosine and urinary 8-OH-deoxyguanosine. GHD was diagnosed using Growth Hormone-Releasing Hormone 50µg iv+arginine 0,5 g/Kg test, with a peak GH response <9 µg /L when BMI was <30 kg/m2 or <4 µg/L when BMI was >30 kg/m2. Patients affected by adult GHD were divided into three groups, total GHD (n = 26), partial GHD (n = 25), and controls (n = 29). Total Antioxidant Capacity, metabolic and hormonal parameters have been determined in separate plasma samples; nitrotryptophan in serum samples; hexanoil-lysine, dityrosine, 8-OH-deoxyguanosine in urine samples. Assessment of hexanoil-lysine exhibited a trend to increase in comparing total GHD vs partial and controls, although not significant. Values of 8-OH-deoxyguanosine did not significantly differ among the three groups. Significant lower levels of dityrosine in partial GHD vs total and controls were found. No significant difference in nitrotriptophan serum levels was found, while significantly greater values of Total Antioxidant Capacity were showed in total and partial GHD vs controls. Thus, our result confirm that oxidative stress is increased both in partial and total adult GHD. The lack of compensation by antioxidants in total GHD may be connected to the complications associated to this rare disorder.

Anabolic Hormones Deficiencies in Heart Failure With Preserved Ejection Fraction: Prevalence and Impact on Antioxidants Levels and Myocardial Dysfunction.

Purpose: In heart failure with reduced ejection fraction, catabolic mechanisms have a strong negative impact on mortality and morbidity. The relationship between anabolic hormonal deficiency and heart failure with preserved ejection fraction (HFpEF) has still been poorly investigated. On the other hand, oxidative stress is recognized as a player in the pathogenesis of HFpEF. Therefore, we performed a cohort study in HFpEF aimed to (1) define the multi-hormonal deficiency prevalence in HFpEF patients; (2) investigate the relationships between hormonal deficiencies and echocardiographic indexes; (3) explore the modulatory activity of anabolic hormones on antioxidant systems. Methods: 84 patients with diagnosis of HFpEF were enrolled in the study. Plasma levels of N-terminal pro-brain natriuretic peptide, fasting glucose, insulin, lipid pattern, insulin-like growth factor-1, dehydroepiandrosterone-sulfate (DHEA-S), total testosterone (T, only in male subjects) were evaluated. Hormonal deficiencies were defined according to T.O.S.C.A. multi-centric study, as previously published. An echocardiographic evaluation was performed. Plasma total antioxidant capacity (TAC) was measured using the system metmyoglobin -H2O2 and the chromogen ABTS, whose radical form is spectroscopically revealed; latency time (LAG) in the appearance of ABTS• is proportional to antioxidants in sample. Results: Multiple deficiencies were discovered. DHEA-S deficiency in 87% of patients, IGF-1 in 67% of patients, T in 42%. Patients with DHEA-S deficiency showed lower levels of TAC expressed by LAG (mean ± SEM 91.25 ± 9.34 vs. 75.22 ± 4.38 s; p < 0.05). No differences between TAC in patients with or without IGF-1 deficiency were found. A trend toward high level of TAC in patients without hormonal deficiencies compared with patients with one or multiple deficiencies was found. Regarding echocardiographic parameters, Left Atrial and Left Atrial Volume Index were significantly higher in patients with low IGF-1 values (mean ± SD 90.84 ± 3.86 vs. 72.83 ± 3.78 mL; 51.03 ± 2.33 vs. 40.56 ± 2.46 mL/m2, respectively; p < 0.05). Conclusions: Our study showed high prevalence of anabolic deficiencies in HFpEF. DHEA-S seems to influence antioxidant levels; IGF-1 deficiency was associated with alteration in parameters of myocardial structure and dysfunction. These data suggest a role of anabolic hormones in the complex pathophysiological mechanisms of HFpEF and could represent the basis for longitudinal studies and investigations on possible benefits of replacement therapy.

Anabolic Hormone Deficiencies in Heart Failure with Reduced or Preserved Ejection Fraction and Correlation with Plasma Total Antioxidant Capacity.

BACKGROUND: While anabolic hormone deficit is a common finding in heart failure with reduced ejection fraction (HFrEF), few data are available in heart failure with preserved ejection fraction (HFpEF). METHODS: Blood samples were collected for metabolic (total cholesterol, HDL cholesterol, LDL cholesterol, creatinine, and glucose) and hormonal (IGF-1, DHEA-S, TSH, fT3, fT4, and T) determination, comparing 30 patients with HFpEF and 20 patients with HFrEF. Total antioxidant capacity was evaluated by using the spectrophotometric method using the latency time in the appearance of the radical species of a chromogen (LAG, sec) as a parameter proportional to antioxidant content of the sample. Echocardiographic parameters were also assessed in the two groups. RESULTS: A high prevalence of testosterone (32% in HFrEF and 72% in HFpEF, p < 0.05) and DHEA-S deficiencies was observed in HFpEF patients. Echocardiographic parameters did not correlate with hormone values. A significant direct correlation between T (r 2 = 0.25, p < 0.05) and DHEA-S (r 2 = 0.19, p < 0.05) with LAG was observed only in HFpEF. CONCLUSION: Anabolic hormone deficiency is clearly shown in HFpEF, as already known in HFrEF. Although longitudinal studies are required to confirm the prognostic value of this observation, our data suggest different mechanisms in modulating antioxidants in the two conditions, with possible therapeutic implications.

The Role of Selenium in Oxidative Stress and in Nonthyroidal Illness Syndrome (NTIS): An Overview.

Selenium is a trace element, nutritionally classified as an essential micronutrient, involved in maintaining the correct function of several enzymes incorporating the selenocysteine residue, namely the selenoproteins. The human selenoproteome including 25 proteins is extensively described here. The most relevant selenoproteins, including glutathione peroxidases, thioredoxin reductases and iodothyronine deiodinases are required for the proper cellular redox homeostasis as well as for the correct thyroid function, thus preventing oxidative stress and related diseases. This review summarizes the main advances on oxidative stress with a focus on selenium metabolism and transport. Moreover, thyroid-related disorders are discussed, considering that the thyroid gland contains the highest selenium amount per gram of tissue, also for future possible therapeutic implication.

Relationships Between Thyroid Hormones, Insulin-Like Growth Factor-1 and Antioxidant Levels in Hypothalamic Amenorrhea and Impact on Bone Metabolism.

Reduced bone mineral density (BMD) in Functional Hypothalamic Amenorrhea (FHA) is mainly related to hypoestrogenism, but other hormonal derangement (reduced conversion of T4-T3 and GH resistance) can play a role. These hormones are involved in antioxidant systems regulation. We evaluated the impact of hormonal alterations, with special focus on low T3 and IGF-1 levels, on antioxidant systems as a link with osteoporosis in FHA. Forty-three FHA patients, 15-34 years, with BMI range 17.3-23.4 kg/m2, were divided in 2 groups according to fT3 levels; group A (n=22), low fT3 (<2.4 pg/ml) and group B (n=21), normal fT3 (≥ 2.4 pg/ml). We evaluated hormonal parameters (fT3, fT4, TSH, IGF-1, FSH, LH, estradiol, DHEAS, testosterone, cortisol), bone metabolism (calcium, phosphorus, 25-OH Vitamin D, PTH, ß-crosslaps, bone alkaline phosphatase) and total antioxidant capacity (TAC), expressed as LAG (latency time in radical species appearance using spectrophotometric method). BMD was assessed by DEXA. Group A patients exhibited significantly lower levels of IGF-1 (159.76±14.79 vs. 220.05±15.25 ng/ml) and osteocalcin (17.51±1.14 vs. 21.49±1.56 ng/ml); LAG values were significantly higher in A (66.33±1.74 s) vs. B (54.62±1.74 s). A significant direct correlation was found between both IGF-1 and fT3 with osteocalcin (r²=0.22, p=0.0049 and r²=0.34, p=0.0001, respectively). No difference in LAG between groups according to IGF-1 were found. These data show a correlation between altered bone turnover and low fT3, which is highly prevalent in FHA. Low fT3 levels may contribute to reduced BMD. Oxidative stress could be the link underlying different bone turnover pattern and endocrine dysfunction in FHA.

Circulating irisin levels in heart failure with preserved or reduced ejection fraction: A pilot study.

Irisin, a recently discovered myokine, has been considered a prognostic factor in several cardiovascular diseases. Nevertheless, no data are available on the role of irisin in patients with heart failure (HF), both with preserved (HFpEF) or reduced (HFrEF) ejection fraction. We have therefore evaluated the circulating irisin levels in HFpEF and HFrEF patients, correlating them with metabolic parameters and total antioxidant capacity (TAC), as index of oxidative stress. Irisin was significantly higher in HFpEF than in HFrEF patients (7.72 ± 0.76 vs 2.77 ± 0.77 ng/ml, respectively). An inverse correlation between irisin and TAC was found in HFpEF, but not in HFrEF. Conversely, no correlation was present with HOMA index. These data support the hypothesis that a different pathophysiological mechanism is involved in the two HF subtypes, and oxidative stress modulates irisin secretion.

Oxidative stress in adult growth hormone deficiency: different plasma antioxidant patterns in comparison with metabolic syndrome.

BACKGROUND AND AIMS: Growth hormone deficiency (GHD) is a condition associated with increased cardiovascular risk and insulin-resistance. Oxidative stress (OS) could be a mechanism underlying both these phenomena. In order to investigate plasma antioxidant defenses in such condition, we evaluated adults with GHD, compared with controls and metabolic syndrome patients (MetS), studying plasma total antioxidant capacity (TAC) and coenzyme Q10 (CoQ10, lipophilic antioxidant) levels, both in its oxidized and reduced forms, correlating this data with metabolic and hormonal pattern. MATERIALS AND METHODS: In this case-control study, 51 GHD, 36 controls, and 35 MetS were enrolled. An evaluation of hormonal and metabolic parameters was performed. TAC was measured using the system metmyoglobin -H202 and the chromogen ABTS, whose radical form is spectroscopically revealed; latency time (LAG) in the appearance of ABTS● is proportional to antioxidant in sample. CoQ10 was assayed by electrochemical method. RESULTS: Despite HOMA index was higher in both GHD and MetS (2.2 ± 0.3 and 3.1 ± 0.3 vs. 1.2 ± 0.2 in controls), only in MetS we observed lower LAG levels (64.5 ± 3.1 s vs. 82.8 ± 5.8 in GHD and 80.6 ± 6.6 in controls), suggesting an increased consumption of antioxidants. LAG significantly correlated with uric acid only in MetS (r 2 = 0.65, p < 0.001), suggesting a different pattern of antioxidants. CoQ10 exhibited a trend toward lower levels in GHD, although not significant. CONCLUSIONS: Our data indicate that GHD, although sharing with MetS various metabolic features, including increased HOMA levels, showed a different pattern of plasma antioxidants, suggesting inadequate reactivity toward radical production rather than an antioxidants consumption as in MetS.

Plasmatic and Intracellular Markers of Oxidative Stress in Normal Weight and Obese Patients with Polycystic Ovary Syndrome.

Introduction Insulin resistance (IR) is associated with polycystic ovary syndrome (PCOS). Oxidative stress (OS) is, in turn, related to IR. Studies in PCOS evidenced an increase in OS markers, but they are mainly performed in obese patients, while the complex picture of normal weight PCOS is still poorly investigated. Matherials and Methods To investigate OS in PCOS and relationship with hormonal and metabolic picture, we performed a case-control study in 2 PCOS groups: normal weight (N-PCOS, n=21, age 18-25 ys, mean±SEM BMI 20.7±0.2 kg/m2) and obese (OB-PCOS, n=15, 20-30 ys, BMI 32.8±1.1), compared with control groups matched for BMI: normal (N-C, n=10, 20-30 ys, BMI 21.6±0.9) and obese (OB-C, n=20, 21-31ys, BMI 36.8±1.0). Malondialdehyde (MDA) in blood plasma and peripheral mononuclear cells, obtained by density-gradient centrifugation, was assayed spectrophotometrically by TBARS assay. CoenzymeQ10 (CoQ10) in plasma and cells was assayed by HPLC. Plasma Total Antioxidant Capacity (TAC) was also measured by spectrophotometric method. Results PCOS patients exhibited higher Testosterone levels than controls, but OB-PCOS had highest HOMA (Homeostasis Model Assessment) index, suggesting marked insulin resistance. Despite plasma MDA levels were not significantly different (N-PCOS 3380±346.94 vs. N-C 7 120±541.66; OB-PCOS 5 517.5±853.9 vs. OB. 3 939.66±311.2 pmol/ml), intracellular MDA levels were significantly higher in N-PCOS than controls (mean 3 259±821.5 vs. 458±43.2 pmol/106/cells) and higher than OB-PCOS, although not significantly (1363.1±412.8 pmol/106/cells). Intracellular CoenzymeQ10 was higher in N-PCOS than in N-C, but the highest levels were found in OB-C. Conclusions Our data, while confirming the presence of OS in obese PCOS patients in agreement with literature, suggest that OS could be present also in normal weight PCOS, but it can be revealed in tissue rather than in plasma. The relationship with metabolic status remains to be established, but could be a physiopathological basis for antioxidant treatment in such patients.

Topoisomerases and Anthracyclines: Recent Advances and Perspectives in Anticancer Therapy and Prevention of Cardiotoxicity.

Topoisomerases are ubiquitous enzymes involved in maintaining genomic stability of the cell by regulating the over- or underwinding of DNA strands. Besides their customary functions, topoisomerases are important cellular targets of widely used anticancer drugs. In particular, topoisomerase IIα (Top2α) has been postulated as the primary molecular target of anthracycline's anticancer activity, whereas topoisomerase IIß (Top2ß), the only Top2 present in heart tissue, seems to be involved in the development of anthracycline-induced cardiotoxicity. Noteworthy, cardiotoxicity is the most frequent adverse effect of both conventional and modern anticancer targeted therapy, representing the leading noncancer-related cause of morbidity and mortality in long-term survivors. The molecular mechanisms of anthracyclineinduced cardiotoxicity have been investigated for decades and, despite the numerous mechanistic hypotheses put forward, its aetiology and pathogenesis still remain controversial. This review is aimed at focusing on the double edge sword of topoisomerase-anthracycline interaction, and, in particular, on the potential role of topoisomerases in anthracyclines anticancer activity as well as in the pathogenesis of anthracycline-induced cardiotoxicity.

Thyroid Hormones, Oxidative Stress, and Inflammation.

Inflammation and oxidative stress (OS) are closely related processes, as well exemplified in obesity and cardiovascular diseases. OS is also related to hormonal derangement in a reciprocal way. Among the various hormonal influences that operate on the antioxidant balance, thyroid hormones play particularly important roles, since both hyperthyroidism and hypothyroidism have been shown to be associated with OS in animals and humans. In this context, the nonthyroidal illness syndrome (NTIS) that typically manifests as reduced conversion of thyroxine (T4) to triiodothyronine (T3) in different acute and chronic systemic conditions is still a debated topic. The pathophysiological mechanisms of this syndrome are reviewed, together with the roles of deiodinases, the enzymes responsible for the conversion of T4 to T3, in both physiological and pathological situations. The presence of OS indexes in NTIS supports the hypothesis that it represents a condition of hypothyroidism at the tissue level and not only an adaptive mechanism to diseases.

Cancer Biomarkers Discovery and Validation: State of the Art, Problems and Future Perspectives.

Cancer is one of the major public health problems worldwide representing the leading cause of morbidity and mortality in industrialized countries. To reduce cancer morbidity and mortality as well as to facilitate the evolution from the traditional "one size fits all" strategy to a new "personalized" cancer therapy (i.e., the right drug to the right patient at the right time, using the right dose and schedule), there is an urgent need of reliable, robust, accurate and validated cancer biomarker tests.Unfortunately, despite the impressive advances in tumor biology research as well as in high-powerful "omics" technologies, the translation of candidate cancer biomarkers from bench to bedside is lengthy and challenging and only a few tumor marker tests have been adopted successfully into routine clinical care of oncologic patients.This chapter provides an updated background on biomarkers research in oncology, including biomarkers clinical uses, and discusses the problems of discovery pipeline, biomarkers failures and future perspectives.

Inhibition of Anthracycline Alcohol Metabolite Formation in Human Heart Cytosol: A Potential Role for Several Promising Drugs.

The clinical efficacy of anthracyclines (e.g., doxorubicin and daunorubicin) in cancer therapy is limited by their severe cardiotoxicity, the etiology of which is still not fully understood. The development of anthracycline-induced cardiomyopathy has been found to correlate with myocardial formation and accumulation of anthracycline secondary alcohol metabolites (e.g., doxorubicinol and daunorubicinol) that are produced by distinct cytosolic NADPH-dependent reductases. The aim of the current study is to identify chemical compounds capable of inhibiting myocardial reductases implied in anthracycline reductive metabolism in an attempt to decrease the production of cardiotoxic C-13 alcohol metabolites. Among the variety of tested compounds (metal chelators, radical scavengers, antioxidants, ß-blockers, nitrone spin traps, and lipid-lowering drugs), ebselen, cyclopentenone prostaglandins, nitric oxide donors, and short-chain coenzyme Q analogs resulted in being effective inhibitors of both doxorubicinol and daunorubicinol formation. In particular, ebselen (as well as ebselen diselenide, its storage form in the cells) was the most potent inhibitor of cardiotoxic anthracycline alcohol metabolites with 50% inhibition of doxorubicinol formation at 0.2 mol Eq of ebselen with respect to doxorubicin concentration. The high efficacy, together with its favorable pharmacological profile (low toxicity, lack of adverse effects, and metabolic stability) portends ebselen as a promising cardioprotective agent against anthracycline-induced cardiotoxicity.

Oxidative stress and metabolic syndrome: Effects of a natural antioxidants enriched diet on insulin resistance.

BACKGROUND & AIMS: Oxidative stress (OS) could play a role in metabolic syndrome-related manifestations contributing to insulin resistance (IR). The aim of the present study was to gain insight the relationships between OS, IR and other hormones involved in caloric balance, explaining the effects of a natural antioxidant-enriched diet in patients affected by metabolic syndrome. METHODS: We investigated the effects of dietary antioxidants on IR, studying 53 obese (20 males and 33 females, 18-66 years old, BMI 36.3 ± 5.5 kg/m2), with IR evaluated by Homeostasis Model Assessment (HOMA)-index, comparing 4 treatments: hypocaloric diet alone (group A) or plus metformin 1000 mg/daily (group B), natural antioxidants-enriched hypocaloric diet alone (group C) or plus metformin (group D). A personalized program, with calculated antioxidant intake of 800-1000 mg/daily, from fruit and vegetables, was administered to group C and D. The glycemic and insulinemic response to oral glucose load, and concentrations of total-, LDL- and HDL-cholesterol, triglycerides, uric acid, C reactive protein, fT3, fT4, TSH, insulin-like growth factor 1 were evaluated before and after 3-months. Plasma Total antioxidant capacity was determined by H2O2-metmyoglobin system, which interacting with the chromogen ABTS generates a radical with latency time (LAG) proportional to antioxidant content. RESULTS: Despite a similar BMI decrease, we found a significant decrease of HOMA and insulin peak only in group B and D. Insulin response (AUC) showed the greatest decrease in group D (25.60  ±  8.96%) and was significantly lower in group D vs B. No differences were observed in glucose response, lipid metabolism and TAC (expressed as LAG values). TSH values were significantly suppressed in group D vs B. CONCLUSIONS: These data suggest that dietary antioxidants ameliorate insulin-sensitivity in obese subjects with IR by enhancing the effect of insulin-sensitizing drugs albeit with molecular mechanisms which remain yet to be elucidated.

Thyroid hormones and antioxidant systems: focus on oxidative stress in cardiovascular and pulmonary diseases.

In previous works we demonstrated an inverse correlation between plasma Coenzyme Q10 (CoQ10) and thyroid hormones; in fact, CoQ10 levels in hyperthyroid patients were found among the lowest detected in human diseases. On the contrary, CoQ10 is elevated in hypothyroid subjects, also in subclinical conditions, suggesting the usefulness of this index in assessing metabolic status in thyroid disorders. A Low-T3 syndrome is a condition observed in several chronic diseases: it is considered an adaptation mechanism, where there is a reduction in pro-hormone T4 conversion. Low T3-Syndrome is not usually considered to be corrected with replacement therapy. We review the role of thyroid hormones in regulation of antioxidant systems, also presenting data on total antioxidant capacity and Coenzyme Q10. Published studies suggest that oxidative stress could be involved in the clinical course of different heart diseases; our data could support the rationale of replacement therapy in low-T3 conditions.