The effect of organic acids on phytohaemagglutinin-activated proliferation of human lymphocytes in vitro |
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| Affiliation: | 1. Faculty of Science and Technology, Division of Molecular Science, Gunma University, 1-5-1 Tenjin-cho, Kiryu, Gunma 376-8515, Japan;2. Gunma Sericultural Technology Center, 1-1-1 Ohte-machi, Maebashi, Gunma 371-8570, Japan;3. Department of Anesthesiology, Graduate School of Medicine, Gunma University, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan;4. Collaboration Promotion Unit, Global Research Cluster, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan;5. Chemical Resource Development Research Unit, RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan;6. Transgenic Silkworm Research Center, National Institute of Agrobiological Sciences, 1-2 Owashi, Tsukuba, Ibaraki 305-8634, Japan;1. Sanofi, LGCR Chemistry, 65926 Frankfurt am Main, Germany;2. University of Hamburg, Department of Chemistry, Pharmaceutical and Medicinal Chemistry, Bundesstraße 45, 20146 Hamburg, Germany;1. Department of Chemistry and Biochemistry, University of Texas at Arlington, 700 Planetarium Place, Arlington, TX, 76019, USA;2. Millipore-Sigma, Bellefonte, PA, 16823, USA;3. Institut des Sciences Analytiques, Université de Lyon 1, CNRS, 5 rue de la Doua, 69100, Villeurbanne, France;1. Department of Nuclear Medicine, General University Hospital and First Faculty of Medicine, Charles University, Praga, República Checa;2. Department of Radiology, General University Hospital and First Faculty Medicine, Charles University, Praga, República Checa;3. Department of Paediatrics, Second Faculty of Medicine, Charles University in Prague and University Hospital Motol, Praga, República Checa;4. Department of Medical Physics, General University Hospital, Praga, República Checa;1. Departamento de Química, Universidad Nacional de Río Cuarto, 5800 Río Cuarto, Argentina;2. IMIBIO – CONICET – Fac. de Química, Bioquímica y Farmacia, Área de Química Física, UNSL, 5700 San Luis, Argentina |
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| Abstract: | The present study assesses the effects of 25 organic acids on in vitro proliferation of human peripheral lymphocyte stimulated with phytohaemagglutinin (PHA). Lymphocytes were cultured in flat-bottomed 96-well microplates at 37°C for 96 h in the presence of the mitogen and of one acid. The concentrations of organic acids tested in the cultures were from 1 to 5 mM, corresponding to those usually found in the blood of patients with organic acidaemias. Cellular growth was measured by the incorporation of 6[3H]-thymidine into cellular DNA. We observed that tiglic (2-methylcrotonic), α-keto-β-methylvaleric, aminoadipic, sebacic and alpha-ketoisocaproic acids strongly inhibited lymphocyte DNA synthesis, whereas α-ketoisovaleric, propionic, α-hydroxy-β-methylvaleric, α-methylbutyric and isobutyric acids moderately suppressed DNA synthesis. Lactic and ethylmalonic acids, however, stimulated DNA synthesis. The most inhibitory acids were added to cultures at different times after the beginning of the incubation period. Except for tiglic acid, whose action persisted even after 48 h from the onset of cultures, the others acted only when added during the first 24 h. The present study demonstrated that organic acids modulate DNA synthesis in mitogen-stimulated human lymphocytes. |
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