Search

Context: Peroxynitrite (ONOO(-)) formation triggers oxidative/nitrative stress and contributes to exacerbated myocardial ischemia/reperfusion (MI/R) injury. Catalpol, an iridoid glycoside, abundantly found in the roots of Rehmannia glutinosa L. that is included in the family Phrymaceae in the order Lamiales, endemic to China, was found to have neuroprotective effects. However, the effect of catalpol on MI/R injury has not been identified., Objective: This study investigated whether catalpol attenuates oxidative/nitrative stress in acute MI/R., Materials and Methods: Adult male rats were subjected to 30 min of myocardial ischemia and 3 h of reperfusion and were treated with saline, catalpol (5 mg/kg, i.p., 5 min before reperfusion) or catalpol plus wortmannin (15 µg/kg intraperitoneally injected 15 min before reperfusion)., Results: Pretreatment with catalpol significantly improved cardiac functions, reduced myocardial infarction, apoptosis and necrosis of cardiomyocytes after MI/R (all p < 0.05). Meanwhile, ONOO(-) formation was markedly reduced after catalpol treatment (3.01 ± 0.22 vs. 4.66 ± 0.53 pmol/mg protein in vehicle, p < 0.05). In addition, catalpol increased Akt and endothelial nitric oxide synthase phosphorylation, nitric oxide (NO) production, anti-oxidant capacity and reduced MI/R-induced inducible nitric oxide synthase expression and superoxide anion (·O(2)(-)) production in I/R hearts. PI3K inhibitor wortmannin not only blocked catalpol-induced Akt activation, but also attenuated all the beneficial effects of catalpol. Suppression of ONOO(-) formation by either catalpol or an ONOO(-) scavenger uric acid (5 mg/kg) reduced myocardial infarct size in MI/R rats., Discussion and Conclusion: In conclusion, catalpol affords cardioprotection against MI/R insult by attenuating ONOO(-) formation, which is attributable to increased physiological NO and decreased ·O(2)(-) production.

Background and Aims: In obesity, oxidative stress is responsible for the aberrant production of adipokines such as adiponectin, plasminogen activator inhibitor (PAI)-1 and interleukin-6 (IL-6), which is causally associated with obesity-related inflammation, insulin resistance and cardiovascular disease. However, the signaling transduction pathways participating in adipokine dysregulation induced by oxidative stress are largely unknown. Thus, the aim of the present study was to identify possible involved signaling pathways., Methods: 3T3-L1 cells were differentiated into adipocytes and underwent oxidative stress by exposure to extraneous H(2)O(2). Quantitative PCR and immunoassays were performed to determine mRNA and protein levels of adipokines (adiponectin, PAI-1 and IL-6), respectively. Possible signaling pathways involved were high-throughout identified by Bioplex phosphoprotein assays and subsequently confirmed by inhibition of the targeted protein kinases such as Akt, ERK1/2, JAK/STAT, JNK, and p70 S6K, respectively., Results: H(2)O(2) markedly suppressed adiponectin mRNA expression as well as protein secretion; however, it enhanced PAI-1 and IL-6 production in mature adipocytes. Akt,JAK/STAT and ERK1/2 participated in the H(2)O(2)-induced increase of PAI-1 and IL-6 expression, whereas adiponectin expression was reduced by H(2)O(2) via Akt and JAK/STAT., Conclusions: Akt and JAK/STAT are congenerous pathways through which oxidative stress downregulates adiponectin and upregulates PAI-1 and IL-6 expression. ERK1/2 participates not in H(2)O(2)-induced decrease of adiponectin expression, but in the increase of PAI-1 and IL-6.

The purpose of the present study was to explore aging-associated cardiac dysfunction and the possible mechanism by which swimming exercise modulates cardiac dysfunction in aged mice. Aged mice were divided into two groups: i) Aged mice; and ii) aged mice subjected to swimming exercises. Another cohort of 4-month-old male mice served as the control group. Cardiac structure and function in mice were analyzed using hematoxylin and eosin staining, and echocardiography. The levels of oxidative stress were determined by measuring the levels of superoxide dismutase, malondialdehyde and reactive oxygen species (ROS). Levels of the endoplasmic reticulum (ER) stress-related protein PKR-like ER kinase, glucose-regulated protein 78 and C/EBP homologous protein were determined to evaluate the level of ER stress. The aged group exhibited an abnormal cardiac structure and decreased cardiac function, both of which were ameliorated by swimming exercise. The hearts of the aged mice exhibited pronounced oxidative and ER stress, which were ameliorated by exercise, and was accompanied by the reactivation of myocardial cGMP and suppression of cGMP-specific phosphodiesterase type 5 (PDE5). The inhibition of PDE5 attenuated age-induced cardiac dysfunction, blocked ROS production and suppressed ER stress. An ER stress inducer abolished the beneficial effects of the swimming exercise on cardiac function and increased ROS production. The present study suggested that exercise restored cardiac function in mice with age-induced cardiac dysfunction by inhibiting oxidative stress and ER stress, and increasing cGMP-protein kinase G signaling. [ABSTRACT FROM AUTHOR]