Use of proliferation tests to evaluate the effects of complexing agents on beryllium toxicity.

Abstract : Occupational exposure to beryllium may cause chronic beryllium disease (CBD), a granulomatous interstitial pneumonitis caused by a cell-mediated immune response with delayed hypersensitivity initiated by an electrostatic interaction with the MHC class II human leukocyte antigen (HLA). Increased research efforts focus on the development of a CBD treatment by chelation therapy. This work presents an in vitro evaluation of the beneficial effects of beryllium chelation with different organic substrates. We have used a standard beryllium lymphocyte proliferation test (BeLPT) adapted for mouse splenocytes. Three complexing agents, 4,5-dihydroxy-1,3-benzenedisulfonic acid (tiron), nitrilotripropionic acid (NTP) and nitrilotriacetic acid (NTA), were tested using different protocols of the splenocyte proliferation test (SPT). We studied their corrective effect (beryllium pre-exposed splenocytes), their protective effect (ligand pre-exposed splenocytes) and their combined effects at fixed Be:L ratio of 1:2, at fixed Be concentration and at fixed L concentration. We also studied the effect of tiron in preventing splenocyte sensitization to beryllium. All three complexing agents showed a corrective effect and proved efficient in the combined effects, except NTA in the fixed Be:L ratio. Only NTP and tiron showed a significant protection at lower beryllium concentrations, while NTA was not significant. Splenocytes pre-exposed to chelated beryllium did not show sensitization while splenocytes pre-exposed to beryllium were sensitized. We observed a strong correlation between the efficiency of the complexing agent and its affinity towards beryllium. Both tiron and NTP showed a similar affinity towards the beryllium ion that is 10(7) higher than that of NTA.
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Submitted on : Thursday, May 2, 2013 - 3:55:13 AM
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Chadi H Stephan, Sébastien Sauvé, Michel Fournier, Pauline Brousseau. Use of proliferation tests to evaluate the effects of complexing agents on beryllium toxicity.. Journal of Applied Toxicology, Wiley, 2009, 29 (1), pp.27-35. ⟨10.1002/jat.1378⟩. ⟨pasteur-00819642⟩

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