Hematology profile, serum clinical chemistry changes and thiodiglycol levels following sulfur mustard exposure in African green monkeys
 
Holmes, W.W., DeLion, M.T., Capacio, B.R., Anderson, D.R.
Sulfur mustard is a chemical warfare agent that is best known as a blistering agent. Research has shown that sulfur mustard affects hematology constituents and most notably leukocytes in exposed individuals. In the present study, we examined clinical blood chemistry constituents in African green monkeys (AGMs; Chlorocebus aethiops) exposed to sulfur mustard. To establish normal cell count and levels of blood chemistry constituents in male AGMs (N=7; 4-7 kg), 1.5 mL blood samples were collected from the saphenous vein twice a week for three weeks. An aliquot of whole blood was analyzed for complete blood count and a cell differential count. The remainder was centrifuged with the resulting serum analyzed for clinical chemistries. These same animals were then challenged with a 1.0 mg/kg intravenous injection of sulfur mustard. Just prior to exposure, a 1.5 mL blood sample was taken and analyzed; subsequent 1.5 mL blood draws were taken three times a week for 30 days after sulfur mustard exposure. Residual whole blood was also analyzed for thiodiglycol (TDG), which is released from blood protein adducts formed upon exposure to sulfur mustard, using a recently developed gas chromatography-mass spectrometry method. Complete blood count analysis showed a reduction in lymphocytes (~70 %) typically observed at 1 day postexposure, reaching a nadir of 460 cells/uL (78 % decrease) at about 4 days postexposure. In contrast, the absolute neutrophil counts (ANC) generally rose 1 day postexposure and then began to drop with a nadir (mean 143 cells/uL) reached on day 7. Blood chemistry analysis showed significant increases in alanine transaminase (ALT), aspartate transaminase (AST), blood urea nitrogen (BUN), creatine kinase (CK), and lactate dehydrogenase (LDH) one day after sulfur mustard exposure with levels rising 93, 189, 75, 721, and 114 % above control levels, respectively. These showed a biphasic pattern with a second peak 32, 101, 75, 330, and 94 %, respectively, occurring between days 7 and 16. Serum total bilirubin (TBIL) levels showed a significant increase at day 4 with a lower peak on day 14. Alkaline phosphate (ALP) levels increased on day 7 by 33 % over controls and peaked with significant differences from control on days 18 (+65 %) and 21 (+70 %). Analysis also showed significant decreases in albumin (ALB), total protein (TP), and calcium (CA) levels. ALB levels decreased significantly starting at day 7 and lasting through day 23, reaching a nadir of 3.67 g/dL (-20 %) at day 11 compared with a control level of 4.58 g/dL. TP levels revealed a similar pattern, with significant decreases observed from day 9 through day 21, with a nadir of 5.92 g/dL (-14 %) compared with a control level of 6.93 g/dL. CA levels also decreased with a significant drop in level 1 day after sulfur mustard exposure, and also at days 4 through day 16. Clinically, increases in ALP, ALT, AST, TBIL, BUN, CK, and LDH and decreases in ALB, TP, and CA, are indicative of cellular injury in the liver, kidneys, and in the GI tract. Analysis of TDG in blood revealed a peak at day 1 and a two-phase exponential decay through the sampling period. TDG was still detectable after 30 days. A comparison of the TDG and lymphocyte data revealed a very strong inverse relationship between the two (R squared = 0.86). In conclusion, observations of these clinical chemistries, TDG levels and lymphocyte counts can be used for clinical diagnosis of sulfur mustard exposure and be indicative of impending neutropenia.
Proceedings of the medical defense bioscience review, 2004
213-1
 
© Copyright 2007 Joshua P. Gray