Grape Seed Extract-Cardiac Impact and Drug Interaction

描述（由申请人提供）：据商业报道，抗氧化剂可减缓心脏病的进展或严重程度。因此，许多传统医疗保健的患者正在服用维生素，矿物质和植物性抗氧化剂补充剂。然而，对其潜在作用机制知之甚少，混淆了安全性和疗效评价。植物药代表了植物化学物质的复杂混合物，其中任何一种都可能与处方药物方案相互作用并改变其生物效应。在某些疾病状态或医疗干预中，这些相互作用可能对患者健康和治疗有害。心脏病通常涉及心脏缺血/再灌注损伤。缺血/再灌注损伤发生在心脏首先被剥夺然后重新供氧，产生破坏性的活性氧（ROS）。缺血/再灌注损伤发生在心脏病的整个范围内-在充血性心力衰竭中以微妙的慢性方式发生，或者在心脏外科手术中以急性方式发生。缺血/再灌注损伤是 通过预处理降低，预处理通过短暂的缺氧或通过药物如阿片类药物预处理发生。阿片类止痛药用于急诊和外科手术。阿片类药物心脏保护作用的机制之一涉及产生低水平的ROS预处理。因此，ROS淬灭抗氧化剂可能会改变阿片类药物的心脏保护作用。合成抗氧化剂已被证明在实验上降低阿片类药物的心脏保护作用，但没有发表的研究调查了膳食抗氧化剂补充剂的潜在影响。我们的研究将利用标准化的葡萄籽提取物IH 636，富含抗氧化剂原花青素。使用兔心肌细胞和整个心脏程序，我们将确定三周的IH 636补充是否影响心脏应激防御蛋白或抗氧化储备的表达。我们还将确定心脏膜的完整性，细胞代谢，心脏功能和整体活力。同时，我们将使用相同的终点评估缺血/再灌注条件下IH 636的心脏效应。最后，利用阿片机制的知识，我们提出的研究将评估IH 636补充剂是否与阿片心脏保护相互作用，以及这种相互作用的性质。对于葡萄籽提取物补充剂，作用机制和阿片类药物相互作用目前尚不清楚。考虑到这种植物提取物的使用越来越多，必须提高对安全性和有效性的认识。

DESCRIPTION (provided by applicant): Antioxidants are commercially reported to slow the advance or severity of heart disease. As such, many patients of conventional health care are consuming antioxidant supplements from vitamins, minerals, and botanicals. However, little is understood of their potential mechanisms of action, confounding safety and efficacy evaluations. Botanicals represent a complex blend of phytochemicals, any of which may interact with prescribed drug regimens and alter their biological effects. In certain diseased states or medical interventions, these interactions could be deleterious to patient health and treatment. Heart disease commonly involves cardiac ischemia/reperfusion damage. Ischemia/reperfusion damage occurs when the heart is first denied then re-supplied with oxygen, generating damaging reactive oxygen species(ROS). Ischemia/reperfusion injury occurs across the span of heart disease - in a subtle, chronic fashion with congestive heart failure, or in an acute fashion as with cardiac surgical procedures. Ischemia/reperfusion damage is lowered through preconditioning, which occurs through brief periods of oxygen deprivation or through pretreatment with drugs such as opioids. Opioid pain-killers are used in emergent and surgical settings. One mechansism of opioid cardioprotection involves the generation of low levels of preconditioning ROS. Thus, ROS-quenching antioxidants may alter opioid cardioprotection. Synthetic antioxidants have been shown to experimentally decrease opioid cardioprotection, but no published studies have investigated the potential impact of dietary antioxidant supplementation. Our studies will utilize a standardized grape seed extract IH636, rich in antioxidant proanthocyanidins. Using rabbit cardiac myocyte and whole heart procedures, we will determine if three weeks of IH636 supplementation affects the expression of cardiac stress defense proteins or antioxidant reserve. We will also determine cardiac membrane integrity, cellular metabolism, heart function, and overall viability. In concert, we will evaluate cardiac effects of IH636 under ischemia/reperfusion conditions using the same endpoints. Finally, using knowledge of opioid mechansisms, our proposed studies will evaluate if IH636 supplementation interacts with opioid cardioprotection, and the nature of this interaction. For grape seed extract supplementation, both mechanisms of action and opioid interaction are currently unknown. Considering the increasing use of this botanical extract, improved knowledge of safety and efficacy is imperative.