Abstract

A multi-component solution, containing α-ketoglutaric acid (α-KG), 5-hydroxymethylfurfural (5-HMF), N-acetyl-seleno-l-methionine (NASeLM), and N-acetyl-l-methionine (NALM) as active ingredients, has been tested considering its supposed antioxidative effect with respect to heart transplantations. Oxidative stress was induced on isolated rat hearts through occlusion of a coronary artery and in chicken heart tissue through hydrogen peroxide. Both heart types were analyzed and the oxidative stress markers malondialdehyde (MDA) and carbonyl proteins (CPs) were determined via HPLC/UV–Vis. In both approaches, it was found that treatment with the multi-component solution led to a lower amount of MDA and CPs compared to a negative control treated with Krebs–Ringer solution (KRS). Further investigation on chicken heart tissue identified α-KG as antioxidative component in these experiments. However, numerous factors like arrhythmia, vessel dilatation, and minimization of oxidative stress effects play an important role for successful transplantation. Therefore, the investigated multi-component solution might be a novel approach against oxidative stress situations, for example at ischemia reperfusion injury during heart transplantations.

Highlights

  • Graft failure is a severe problem after heart transplantations

  • The active ingredients of the multi-component solution are α-ketoglutaric acid (α-KG), 5-hydroxymethylfurfural (5-HMF), N-acetyl-seleno-l-methionine (NASeLM), and N-acetyl-l-methionine (NALM). α-KG and 5-HMF are described as directly antioxidative agents under different conditions [5,6,7,8]

  • MDA showed a rise of about 160% through oxidative stress, carbonyl proteins (CPs) increased about 950% compared to hearts without oxidative stress

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Summary

Introduction

Graft failure is a severe problem after heart transplantations. It is caused due to the excessive formation of reactive oxygen and nitrogen species (ROS/RNS) during the peri-surgical process including explantation, transport, and implantation.ROS generation occurs mainly at reperfusion when molecular oxygen is reintroduced into the ischemic area. It is caused due to the excessive formation of reactive oxygen and nitrogen species (ROS/RNS) during the peri-surgical process including explantation, transport, and implantation. ROS can react with nitric oxide (NO) and thereby form reactive nitrogen species (RNS)—for example peroxynitrite [1, 2]. A novel approach to overcome this problem is a multicomponent solution in combination with angiotensin-(1-7). The active ingredients of the multi-component solution are α-ketoglutaric acid (α-KG), 5-hydroxymethylfurfural (5-HMF), N-acetyl-seleno-l-methionine (NASeLM), and N-acetyl-l-methionine (NALM). NALM is a source of methionine, while NASeLM is a source of selenium. Both methionine and selenium are contributors of the body’s antioxidative defense system via regulation of antioxidative enzymes [9,10,11,12]

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