Showing papers by "Elisabetta Meucci published in 2012"

Biochemical alterations in semen of varicocele patients: a review of the literature.

Abstract: Oxidative stress is a mechanism underlying different kinds of infertility in human males. However, different results can be observed in relation to the method used for its evaluation. Varicocele patients show a number of biochemical abnormalities, including an altered distribution of coenzyme Q between seminal plasma and sperm cells and also an apparent defect in the utilization of antioxidants. Moreover, an influence of systemic hormones on seminal antioxidant system was observed too. Finally, the effects of surgical treatment on oxidativestress indexes and the possible usefulness of some medical therapies, like coenzyme Q supplementation, are discussed. In conclusion, published data show a role of oxidative stress in varicocele-related male infertility, but at present we do not know the precise molecular mechanisms underlying these phenomena.

Anthracyclines and mitochondria.

Abstract: Anthracyclines remain the cornerstone in the treatment of many malignancies including lymphomas, leukaemias, and sarcomas. Unfortunately, the clinical use of these potent chemotherapeutics is severely limited by the development of a progressive dose-dependent cardiomyopathy that irreversibly evolves toward congestive heart failure. The molecular mechanisms responsible for anthracycline anticancer activity as well as those underlying anthracycline-induced cardiotoxicity are incompletely understood and remain a matter of remarkable controversy. Anthracyclines have long been considered to induce cardiotoxicity by mechanisms different from those mediating their anticancer activity. In particular, anthracycline antitumor efficacy is associated with nuclear DNA intercalation, topoisomerase II inhibition and drug-DNA adducts formation, whereas the cardiotoxicity is prevalently ascribed to oxidative stress and mitochondrial dysfunction. At present, however, the view that distinct mechanisms are implied in anticancer and cardiotoxic responses to anthracycline therapy does not seem fully convincing since beneficial (anticancer) and detrimental (cardiotoxic) effects are to some extent overlapping, share the subcellular organelle targets, the molecular effectors and the pathophysiological processes (i.e. DNA strand breaks, oxidative stress, signalling pathways, mitochondrial dysfunctions, apoptosis etc.).

Hypothyroidism, Oxidative Stress and Reproduction

Abstract: In women, both hyperand hypo-thyroidism may result in menstrual disturbances. In hyperthyroidism the most common manifestations are simple oligomenorrhea and anovulatory cycles. Hypothyroidism results in changes in cycle length, amount of bleeding, and usually is associated with abnormal menstrual cycles characterized mainly by polymenorrhea and anovulatory cycles (Krassas et al., 1999). Also subclinical hypothyroxinemia can be associated with short luteal phase and insufficient progesterone secretion (Bohnet et al., 1981); similar pictures are present in a variety of situations characterized by low T3 levels (malnutrition, chronic illness, exercise), known as “nonthyroidal illness” (De Groot, 2006).

Relationship between plasma antioxidants and thyroid hormones in chronic obstructive pulmonary disease

Abstract: BACKGROUND: A low-T₃ syndrome is observed in chronic diseases, but its treatment is still debated. Chronic obstructive pulmonary disease (COPD) has not been conclusively studied under this aspect. COPD is a complex condition, which cannot be considered a lung-related disorder, but rather a systemic disease also associated to increased oxidative stress. We evaluated thyroid hormones and antioxidant systems, the lipophilic Coenzyme Q10 (CoQ₁₀) and total antioxidant capacity (TAC) in COPD patients to reveal the presence of a low-T₃ syndrome in COPD and investigate the correlation between thyroid hormones, lung function parameters and antioxidants. METHODS: We studied: 32 COPD patients and 45 controls, evaluating thyrotropin (TSH), free-triiodotyronine (fT₃), free-tetraiodotyronine (fT₄), CoQ₁₀ (also corrected for cholesterol) and TAC. CoQ₁₀ was assayed by HPLC; TAC by the metmyoglobin-ABTS method and expressed as latency time (LAG) in radical species appearance. RESULTS: We found significantly lower LAG values, fT₃ and fT₄ levels and significantly higher TSH in COPD patients vs. controls. LAG values significantly correlated with fT₃ concentration. 12 out of 32 patients exhibited fT₃ levels lower than normal range. So we divided COPD patients in 2 groups on the basis of the fT₃ concentration (normal fT₃ COPD and low fT₃ COPD). We observed lower LAG values in normal fT₃-COPD, compared to healthy subjects, with a further significant reduction in low fT₃-COPD patients. Moreover higher TSH concentration was present in normal fT₃-COPD, compared to healthy subjects, with a further significant increase in low fT₃-COPD patients. CoQ₁₀/cholesterol ratio was higher in low fT₃-COPD vs. normal fT₃-COPD, with a nearly significant difference. CONCLUSIONS: These data seem to indicate an increased oxidative stress in low fT₃-COPD and a role of fT₃ in modulating antioxidant systems. However low fT₃ levels are joined to metabolic indexes of true hypothyroidism, suggesting that elevated CoQ₁₀ expresses a reduced tissue utilization. These data might suggest the need of thyroid replacement therapy in such a condition.

Cancer Stem Cell and ATP-Binding Cassette: Which Role in Chemoresistance?

Abstract: Chemoresistance is mediated through a variety of cellular alterations including, among others, reduced drug accumulation, decreased levels of protein targets, change in drugs metabolism, and break down of apoptotic signaling. The capability to acquire resistance to multiple compounds by cancer stem cells (CSCs), called multidrug resistance (MDR), is attributed to overexpression of ATP-binding cassette (ABC) transporters that extrude several substrates from the cell using ATP as driving force. ABC proteins are involved in the exclusion from the cells of several physiological compounds and/or xenobiotics. Three members of the ABC protein superfamily, ABCB1, ABCC1, and ABCG2 which play a major role in mediating clinical development of the MDR phenotype are also implicated in protection from chemotherapy of CSCs. In brief, the most intriguing characteristic of CSCs is their ability to acquire resistance to multiple anticancer agents that is often mediated by overexpression of ABC transporters which remove drugs out of the cell against a concentration gradient. Modulation of ABC transporters, using inhibitors in a combination therapy with cytostatic agents, could be a winning strategy to mitigate CSCs’ chemoresistance and open the door to apoptotic pathways of these cells in order to prevent relapse of tumor metastases.