ABSTRACT
We studied the effect of short-term nadolol administration on the reactive oxygen species (ROS) generation by polymorphonuclear leukocytes and mononuclear cells in 8 normal subjects. At a oral dose of 40 mg/day for 5 days, nadolol produced a decrease in the ROS generation by leukocytes. ROS generation by polymorphonuclear leukocytes decreased by 38% from 134 +/- 44 mV at baseline to 83 +/- 34 mV after 5 days (p = 0.005), and ROS generation by mononuclear cells decreased by 33% from 174 +/- 69 mV at baseline to 117 +/- 55 mV after 5 days (p = 0.015). There was also a significant reduction in linoleic acid oxidation as reflected by the lower levels of 9- and 13- hydroxy-octadecadienoic acid after 5 days. There was no change in the plasma thiobarbituric acid-reacting substances, a less sensitive index of oxidative damage to lipids. There was also no significant change in the levels of metatyrosine and orthotyrosine, which are known indexes of oxidative damage to amino acids and proteins. The absence of a significant change in metatyrosine, orthotyrosine, and thiobarbituric acid-reacting substances may reflect the short duration of nadolol administration and the decreased ROS load. Because ROS may induce lipid peroxidation, this inhibitory effect of nadolol on ROS generation by leukocytes and linoleic acid oxidation may inhibit low-density lipoprotein oxidation and thus atherogenesis. This effect may partly explain the favorable outcomes observed in patients with coronary artery disease on long-term beta-blocker therapy.
Subject(s)
Adrenergic beta-Antagonists/pharmacology , Leukocytes, Mononuclear/drug effects , Linoleic Acid/metabolism , Nadolol/pharmacology , Neutrophils/drug effects , Reactive Oxygen Species/metabolism , Administration, Oral , Adult , Chromatography, High Pressure Liquid , Female , Humans , Leukocytes, Mononuclear/metabolism , Male , Neutrophils/metabolism , Oxidation-Reduction/drug effects , Phenylalanine/blood , Thiobarbituric Acid Reactive Substances/metabolism , Tyrosine/bloodABSTRACT
The bone-marrow microenvironment has a decisive role in maintaining haemopoietic stem cells and regulating their differentiation. In diseases of the haemopoietic system, viz. anaemias and leukemias, the microenvironment has been shown to play a key role. In this paper we show that leukemic cell conditioned medium and sera from CML patients, interact with the in vitro bone-marrow environment and bring about changes which affect the maintenance of normal stem cells.