Iron (III)-mediated degradation of α-asarone and characterization of its major degradation products by UPLC-MS/MS and NMR.

α-Asarone, the main bioactive phytochemicals of Acorus species, is widely used in the treatment of respiratory disorders. The solution stability study of α-asarone was investigated in the presence of various metal ions. α-Asarone was found to be unstable in the presence of the metal ions Fe3+, Cu2+ and Al3+, in which the induction of Fe3+ was highly prone to the degradation of α-asarone. Thus, an iron (III)-mediated forced degradation study of α-asarone was carried out. One oxidative and four dimeric products were formed after the degradation of α-asarone. The complete mass fragmentation patterns for α-asarone and its degradation products (DPs) were established by UPLC-MS/MS in the positive ionization mode, and their structural confirmation was accomplished with 1H and 13C NMR. Then, the mechanistic pathways for the formation of all DPs were postulated. Finally, the oxidation degradation behavior and mechanism of α-asarone in the presence of oxidative stressors viz., hydrogen peroxide and azobisisobutyronitrile were explored.

RXR agonists inhibit oxidative stress-induced apoptosis in H9c2 rat ventricular cells.

Retinoid X receptor (RXR) plays a central role in the regulation of intracellular receptor signaling pathways. We examined its role in regulating oxidative stress-induced apoptosis in H9c2 rat ventricular cells. We showed for the first time that functional RXR protein was downregulated by hydrogen peroxide (H2O2) in H9c2 cardiomyocytes. Natural and synthetic agonists of RXR, 9-cis-RA, and LGD1069 respectively, prevented H2O2-triggered apoptosis, and this anti-apoptotic effect was inhibited by the RXR antagonist HX531. Further investigation into the protective mechanisms of RXR demonstrated that H2O2-induced loss of mitochondrial membrane potential, mitochondrial release of cytochrome c and caspase-3 activation were all significantly attenuated by pretreatment with RXR agonists. Furthermore, this protection was associated with a reduction in intracellular reactive oxygen species and an upregulation in catalase activity. Thus, these data indicate that pharmacological activation of RXR exerts protective effects against H2O2-induced apoptosis in H9c2 rat ventricular cells through antioxidant and mitochondria-protective mechanisms.

Gender differences in epicardial and tissue-level reperfusion in patients undergoing primary angioplasty for acute myocardial infarction.

OBJECTIVE: The impact of gender on clinical course after ST-elevation myocardial infarction (STEMI) is not fully understood. We prospectively investigated whether there are gender-related differences in epicardial and myocardial tissue-level perfusion, both of which represent important prognostic determinants in STEMI patients undergoing primary percutaneous coronary intervention (PPCI). METHODS: A total of 594 consecutive non-selected STEMI patients undergoing PPCI were prospectively enrolled. Primary end-point of the study was post-procedural epicardial and myocardial perfusion. Secondary end-points were the 30-day and 6-month composite occurrence of major adverse cardiac events (MACE). RESULTS: Women with STEMI had higher risk factor profiles than men. Although PPCI achieved equal rates of successful epicardial reperfusion, women tended to have impaired microvascular reperfusion as reflected by lower rates of normal TIMI myocardial perfusion grade (P=0.007) and complete ST-segment resolution (P=0.079). After adjustment for the risk profiles, multivariable analysis showed that gender itself was not an independent predictor of impaired microvascular reperfusion. Both female gender and impaired myocardial reperfusion were independent predictors of 30-day MACE, whereas gender lost its prognostic significance for 6-month MACE. Multivariable analysis restricted to female patients identified incomplete ST-segment resolution as the strongest determinant of 30-day MACE. CONCLUSION: The differences in microvascular reperfusion after PPCI between women and men are attributed to higher risk profiles in women. Both female gender and impaired myocardial reperfusion were independent predictors of 30-day outcomes after PPCI, emphasizing the importance of successful microvascular reperfusion in the women with STEMI.

Factors affecting thrombolysis in myocardial infarction myocardial perfusion frame count: insights of myocardial tissue-level reperfusion from a novel index for assessing myocardial perfusion.

BACKGROUND: Myocardial tissue-level perfusion failure is associated with adverse outcomes following ST-elevation myocardial infarction (STEMI) despite successful epicardial recanalization. We have developed a new quantitative index-thrombolysis in myocardial infarction (TIMI) myocardial perfusion frame count (TMPFC)--for assessing myocardial tissue level perfusion. However, factors affecting this novel index of myocardial perfusion are currently unknown. METHODS: A total of 255 consecutive STEMI patients undergoing primary angioplasty were enrolled. Myocardial tissue level perfusion was assessed by TMPFC, which measures the filling and clearance of contrast in the myocardium using cine-angiographic frame counting. We differentiate three groups with two cut off values for TMPFC: a TMPFC of 90 frames was the upper boundary of the 95% confidence interval (CI) for the TMPFC observed in normal arteries, and a TMPFC of 130 was the 75th percentile of TMPFC. RESULTS: STEMI patients with TMPFC > 130 frames (68 patients, 26.7%) had higher clinical and angiographic risk factor profiles as well as a higher 30-day MACE rate compared with those with TMPFC ≤ 90 frames and those with TMPFC > 90 and ≤ 130 frames. Multivariable analysis identified that the independent predictors of TMPFC > 130 frames were age ≥ 75 years (OR 2.08, 95%CI 1.21 to 3.58, P = 0.007), diabetes (OR 1.37, 95%CI 1.01 to 1.86, P = 0.042), Killip class ≥ 2 (OR 1.52, 95%CI 1.05 to 2.21, P = 0.027), and prolonged pain-to-balloon time (OR 1.73, 95%CI 1.07 to 2.79, P = 0.013). TMPFC > 130 frames was identified as the strongest independent predictor of 30-day major adverse cardiac event (MACE) (OR 2.77, 95%CI 1.21 to 6.31, P = 0.008), along with age ≥ 75 years (OR 2.19, 95%CI 1.11 to 4.33, P = 0.016), female gender (OR 1.67, 95%CI 1.03 to 2.70, P = 0.038), and Killip class ≥ 2 (OR 1.83, 95%CI 1.07 to 3.14, P = 0.021). CONCLUSIONS: STEMI patients with poor myocardial perfusion assessed by TMPFC had higher risk factor profiles. Advanced age, diabetes, higher Killip class, and longer ischemia time were independent predictors of impaired TMPFC after primary percutaneous coronary intervention. These results emphasize that particular attention should be paid on myocardial microvascular reperfusion in STEMI patients with these risk factors.