AIMS: Doxorubicin is widely used against cancer; however, it can produce heart failure (HF). Among other hallmarks, oxidative stress is a major contributor to HF pathophysiology. The late INa inhibitor ranolazine has proven effective in treating experimental HF. Since elevated [Na+ ]i is present in failing myocytes, and has been recently linked with reactive oxygen species (ROS) production, our aim was to assess whether ranolazine prevents doxorubicin-induced cardiotoxicity, and whether blunted oxidative stress is a mechanism accounting for such protection.\ud \ud METHODS AND RESULT: In C57BL6 mice, doxorubicin treatment for 7 days produced LV dilation and decreased echo-measured fractional shortening (FS). Ranolazine (305 mg/kg/day) prevented LV dilation and dysfunction when co-administered with doxorubicin. Doxorubicin-induced cardiotoxicity was accompanied instead by elevations in atrial natriuretic peptide (ANP), BNP, connective tissue growth factor (CTGF), and matrix metalloproteinase 2 (MMP2) mRNAs, which were not elevated on co-treatment with ranolazine. Alterations in extracellular matrix remodelling were confirmed by an increase in interstitial collagen, which did not rise in ranolazine-co-treated hearts. Levels of poly(ADP-ribose) polymerase (PARP) and pro-caspase-3 measured by western blotting were lowered with doxorubicin, with increased cleavage of caspase-3, indicating activation of the proapoptotic machinery. Again, ranolazine prevented this activation. Furthermore, in HL-1 cardiomyocytes transfected with HyPer to monitor H2 O2 emission, besides reducing the extent of cell death, ranolazine prevented the occurrence of oxidative stress caused by doxorubicin. Interestingly, similar protective results were obtained with the Na+ /Ca2+ exchanger (NCX) inhibitor KB-R7943.\ud \ud CONCLUSIONS: Ranolazine protects against experimental doxorubicin cardiotoxicity. Such protection is accompanied by a reduction in oxidative stress, suggesting that INa modulates cardiac redox balance, resulting in functional and morphological derangements

Higher DII scores, indicating greater inflammatory potential of the diet, were directly associated with LGI, as measured by a composite score of plasma and cellular biomarkers of inflammation. These findings are consistent with the contributing role of diet-mediated inflammation in increasing risk for inflammation-related chronic diseases.

No abstract

Background/Objectives: Antioxidant-rich foods may favorably influence lung function. We examined possible associations between the total dietary antioxidant capacity (TAC) and pulmonary function in a healthy Italian population. Subjects/Methods: Until May 2009, 22 300 persons were randomly recruited from the general population in the Moli-sani project. A sample only including healthy women (5824) and men (5848) was analyzed. TAC was measured in foods by three different assays and the ferric reducing-antioxidant power (FRAP) assay was selected as the better indicator of dietary TAC. The European Investigation into Cancer and Nutrition Food Frequency Questionnaire was used for dietary assessment. The association between quintiles of dietary FRAP and pulmonary indexes was assessed using analysis of variance separately for men and women. Results: After adjustment for confounders, women in the highest quintile of FRAP intake had þ 39 ml forced expiratory volume in the first second (FEV 1 ) and þ 54 ml forced vital capacity, compared with those in the lowest quintile (P for trend p0.006). Stratified analysis showed that this relationship only occurred in women who were premenopausal/never smokers. In this subgroup, the observed effect of higher FRAP intake on FEV 1 was equivalent to an improvement in pulmonary age of 3.3 years. In men, all significant associations between pulmonary function and TAC were lost after adjustment for confounding. Conclusions: Dietary TAC may have a favorable role in respiratory health, particularly in premenopausal/never smoker women.

A higher overall polyphenol content of human diet was associated with better pulmonary function in a general population. The association might be partially mediated by WBC in men.