Abstract
Propranolol is a lipophilic nonselective beta blocker mainly eliminated via the liver. The specific architectural arrangement of the mammalian lung favors the filtration of so-called pneumophilic drugs out of the blood and retention within the tissue, as shown in particular for amphetamine, amiodarone, imipramine, chlorpromazine, propranolol and local anesthetics. In the current study we tested in vitro the susceptibility of freshly isolated rat type II pneumocytes (RTII), rat alveolar macrophages (RAM), human alveolar macrophages (HAM) and A549 human lung adenocarcinoma cell line (A549) to propranolol (0.001-1 mM). Cytotoxicity was evaluated by changes in membrane integrity (lactate dehydrogenase [LDH] assay) and mitochondrial metabolic activity (reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, MTT) after 3-h and 20-h incubation with propranolol. In all tested lung cells, propranolol caused concentration-dependent decreases of MTT reduction and LDH retention in the fraction of attached cells, which was associated with an increase of LDH activity in the medium and in the fraction of non-attached cells. After 3-h incubation, the reduction of MTT was significantly decreased compared with control at > or = 1 x 10(-4) M in HAM, at > or = 5 x 10(-4) M in A549 and significantly decreased of LDH retention in the fraction of attached cells in HAM and in A549 at > or = 5 x 10(-4) M. After 20-h incubation the reduction of MTT was significantly decreased compared with control at > or = 1 x 10(-6) M in RAM, at > or = 5 x 10(-5) M in RTII and HAM and > or = 5 x 10(-4) M in A549. Propranolol caused a significant decrease of LDH retention in the fraction of attached cells (> or = 5 x 10(-5) M, RAM and RTII; > or = 5 x 10(-4) M, HAM and A549). The cytotoxic effect of propranolol in HAM and A549 was more pronounced after prolongation of incubation time (from 3 h to 20 h). These results showed that rat and human lung cells were sensitive to propranolol concentration < or = 1 mM in vitro. We suppose that the damaging action of propranolol on the lungs might be mediated by physicochemical properties of moiety and its pulmonary metabolites.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: Methods and findings in experimental and clinical pharmacology
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
