N-Octanoyl Dopamine, a Non-Hemodyanic Dopamine Derivative, for Cell Protection during Hypothermic Organ Preservation
نویسندگان
چکیده
BACKGROUND Although donor dopamine treatment reduces the requirement for post transplantation dialysis in renal transplant recipients, implementation of dopamine in donor management is hampered by its hemodynamic side-effects. Therefore novel dopamine derivatives lacking any hemodynamic actions and yet are more efficacious in protecting tissue from cold preservation injury are warranted. We hypothesized that variation of the molecular structure would yield more efficacious compounds avoid of any hemodynamic effects. METHODOLOGY/PRINCIPAL FINDINGS To this end, we assessed protection against cold preservation injury in HUVEC by the attenuation of lactate dehydrogenase (LDH) release. Modification of dopamine by an alkanoyl group increased cellular uptake and significantly improved efficacy of protection. Further variation revealed that only compounds bearing two hydroxy groups in ortho or para position at the benzene nucleus, i.e. strong reductants, were protective. However, other reducing agents like N-acetyl cysteine and ascorbate, or NADPH oxidase inhibition did not prevent cellular injury following cold storage. Unlike dopamine, a prototypic novel compound caused no hemodynamic side-effects. CONCLUSIONS/SIGNIFICANCE In conclusion, we demonstrate that protection against cold preservation injury by catecholamines is exclusively governed by strong reducing capacity and sufficient lipophilicity. The novel dopamine derivatives might be of clinical relevance in donor pre-conditioning as they are completely devoid of hemodynamic action, their increased cellular uptake would reduce time of treatment and therefore also may have a potential use for non-heart beating donors.
منابع مشابه
Hypothermic injury: the mitochondrial calcium, ATP and ROS love-hate triangle out of balance.
BACKGROUND/AIMS Catecholamines prevent hypothermic cell death which accounts for severe tissue damage and impaired allograft function after prolonged organ preservation. Here, we identified cellular processes which govern hypothermia-mediated cell death in endothelial cells and how they are influenced by dopamine. METHODS Lactate dehydrogenase assay, intracellular ATP, reactive oxygen species...
متن کاملA review of the role of dopamine receptors and novel therapeutic strategies in non-small cell lung cancer (NSCLC)
Lung cancer is a very aggressive and most deadly cancer in both men and women. Lung cancer is divided into two types of small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). NSCLC is divided into 3 subgroups: adenocarcinoma (AC), squamous cell carcinoma (SqCC) and large cell carcinoma (LCC). Dopamine is involved in controlling motions, cognition, emotions, memory and reward mech...
متن کاملDopamine and lipophilic derivates protect cardiomyocytes against cold preservation injury.
Donor heart allografts are extremely susceptible to prolonged static cold storage. Because donor treatment with low-dose dopamine improves clinical outcome after heart transplantation, we tested the hypothesis that dopamine and its lipophilic derivate, N-octanoyl dopamine (NOD), protect cardiomyocytes from cold storage injury. Neonatal rat cardiomyocytes were treated with dopamine or NOD or lef...
متن کاملHypothermic Blood Substitution: Special Considerations for Protection of Cells during ex vivo and in vivo Preservation
Clinical applications of hypothermia range from ex vivo storage of cells, tissues and organs for transplantation or cell-based therapies to in vivo protection of a patient during complex surgeries that might entail circulatory and/or cardiac arrest. The intent of this brief review is to outline the essential principles of hypothermia applied in the preservation of cells for a multitude of clini...
متن کاملDopamine-Synthesizing Neurons: An Overview of Their Development and Application for Cell Therapy
Cell-gene therapy is a dynamic constituent of novel medical biotechnology. Neurodegenerative disordersin which damage to or demise of specific brain cell types plays central role, are clear examples of diseasecandidate for cell replacement therapy. Dopaminergic (DAergic) neurons biosynthesize dopamine, a vitalneurotransmitter in the central nervous system. Due to the involveme...
متن کامل