Death as a Drug Side Effect in FAERS: Is Glyphosate Contamination a Factor?

Abstract

An analysis of selected datasets from the FDA’s drug Adverse Event Reporting System (FAERS) leads us to hypothesize that glyphosate contamination in both food and drugs is a major contributor to chronic and acute kidney failure respectively. In chronic kidney failure, glyphosate-induced pancreatitis results in the release of trypsin, causing a leaky vasculature. The albumin-bound glyphosate escapes into the tissues, protecting the circulatory system and kidneys but resulting in multiple symptoms related to skin, gut, brain, bones, lungs, etc. The rare and poorly understood acute kidney failure response reported for protamine sulfate and Trasylol? is strikingly similar to that associated with glyphosate poisoning. Both drugs are derived from biological tissues that are plausibly contaminated with glyphosate. These drugs protect from haemorrhage, which leads to retention of glyphosate in the vasculature, are followed by circulatory collapse and a high likelihood of death as an outcome. We support our argument by comparing symptom profiles of selected subsets of FAERS with those related to glyphosate poisoning, anomalous reactions to protamine sulfate, and conditions showing strong statistical time-trend correlations with glyphosate.

Share and Cite:

Seneff, S., Swanson, N., Li, C. and Koenig, G. (2015) Death as a Drug Side Effect in FAERS: Is Glyphosate Contamination a Factor? Agricultural Sciences, 6, 1742-1501. http://dx.doi.org/10.4236/as.2015.612143

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] Nuckols, T.K., Paddock, S.M., Bower, A.G., Rothschild, J.M., Fairbanks, R.J., Carlson, B., Panzer, R.J. and Hilborne, L.H. (2008) Costs of Intravenous Adverse Drug Events in Academic and Nonacademic Intensive Care Units. Medical Care, 46, 17-24.
http://dx.doi.org/10.1097/MLR.0b013e3181589bed
[2] Lazarou, J., Pomeranz, B.H. and Corey, P.N. (1998) Incidence of Adverse Drug Reactions in Hospitalized Patients: A Meta-Analysis of Prospective Studies. The Journal of the American Medical Association, 279, 1200-1205.
http://dx.doi.org/10.1001/jama.279.15.1200
[3] Majewski, M.S., Coupe, R.H., Foreman, W.T. and Capel, P.D. (2014) Pesticides in Mississippi Air and Rain: A Comparison between 1995 and 2007. Environmental Toxicology and Chemistry, 33, 1283-1293.
http://dx.doi.org/10.1002/etc.2550
[4] Chang, F.C., Simcik, M.F. and Capel, P.D. (2011) Occurrence and Fate of the Herbicide Glyphosate and Its Degradate Aminomethylphosphonic Acid in the Atmosphere. Environmental Toxicology and Chemistry, 30, 548-555.
[5] Scribner, E.A., Battaglin, W.A., Gilliom, R.J. and Meyer, M.T. (2007) Concentrations of Glyphosate, Its Degradation Product, Aminomethylphophonic Acid, and Glufosinate in Ground- and Surface-Water, Rainfall, and Soil Samples Collected in the United States, 2001-06S. Geological Survey Scientific Investigations Report 2007-5122.
[6] Coupe, R.H., Kalkhoff, S.J., Capel, P.D. and Gregoire, C. (2012) Fate and Transport of Glyphosate and Aminomethylphosphonic Acid in Surface Waters of Agricultural Basins. Pest. Management Science, 68, 16-30.
http://dx.doi.org/10.1002/ps.2212
[7] Mercurio, P., Flores, F., Mueller, J.F., Carter, S. and Negri, A.P. (2014) Glyphosate Persistence in Seawater. Marine Pollution Bulletin, 85, 385-390.
http://dx.doi.org/10.1016/j.marpolbul.2014.01.021
[8] Aris, A. and Leblanc, S. (2011) Maternal and Fetal Exposure to Pesticides Associated to Genetically Modified Foods in Eastern Townships of Quebec, Canada. Reproductive Toxicology, 31, 528-533.
http://dx.doi.org/10.1016/j.reprotox.2011.02.004
[9] Krüger, M., Schledorn, P., Schrödl, W., Hoppe, H.-W., Lutz, W. and Shehata, A.A. (2014) Detection of Glyphosate Residues in Animals and Humans. Journal of Environmental & Analytical Toxicology, 4, 2.
[10] Lanaro, R., Costa, J.L., Cazenave, S.O., Zanolli-Filho, L.A., Tavares, M.F. and Chasin, A.A. (2015) Determination of Herbicides Paraquat, Glyphosate and Aminomethylphosphonic Acid in Marijuana Samples by Capillary Electrophoresis. Journal of Forensic Sciences, 60, S241-S247.
http://dx.doi.org/10.1111/1556-4029.12628
[11] Flaum, I. (1977) Contamination of Pharmaceutical Products. Journal of Pharmaceutical Sciences, 67, 1-11.
http://dx.doi.org/10.1002/jps.2600670104
[12] Dunsmuir, L. (2015) Tylenol Maker to Pay $25 mln for Selling Metal-Contaminated Drugs. Reuters Press, March 10. Last accessed September 10, 2015.
http://www.reuters.com/article/2015/03/10/johnson-johnson-tylenol-idUSL1N0WC2E420150310
[13] Royston, D., Bidstrup, B.P., Taylor, K.M. and Sapsford, R.N. (1987) Effect of Aprotinin on Need for Blood Transfusion after Repeat Open-Heart Surgery. The Lancet, 2, 1289-1291.
http://dx.doi.org/10.1016/S0140-6736(87)91190-1
[14] Ray, W.A. and Stein, C.M. (2008) The Aprotinin Story—Is BART the Final Chapter? The New England Journal of Medicine, 358, 2398-2400.
http://dx.doi.org/10.1056/NEJMe0803514
[15] Mangano, D.T., Tudor, I.C. and Dietzel, C. (2006) The Risk Associated with Aprotinin in Cardiac Surgery. The New England Journal of Medicine, 354, 353-365.
http://dx.doi.org/10.1056/NEJMoa051379
[16] Mangano, D.T., Miao, Y., Vuylsteke, A., Tudor, I.C., Juneja, R., Filipescu, D,, Hoeft, A., Fontes, M.L., Hillel, Z., Ott E, Titov, T., Dietzel, C. and Levin, J., Investigators of the Multicenter Study of Perioperative Ischemia Research Group and Ischemia Research and Education Foundation (2007) Mortality Associated with Aprotinin during 5 Years Following Coronary Artery Bypass Graft Surgery. The Journal of the American Medical Association, 297, 471-479.
[17] Schneeweiss, S., Seeger, J.D., Landon, J. and Walker, A.M. (2008) Aprotinin during Coronary-Artery Bypass Grafting and Risk of Death. The New England Journal of Medicine, 358, 771-783.
http://dx.doi.org/10.1056/NEJMoa0707571
[18] Shaw, A.D., Stafford-Smith, M., White, W.D., Phillips-Bute, B., Swaminathan, M.D., Milano, C., Welsby, I.J., Aronson, S., Mathew, J.P., Peterson, E.D. and Newman, M.F. (2008) The Effect of Aprotinin on Outcome after Coronary-Artery Bypass Grafting. The New England Journal of Medicine, 358, 784-793.
http://dx.doi.org/10.1056/NEJMoa0707768
[19] Dietrich, W., Busley, R. and Boulesteix, A.L. (2008) Effects of Aprotinin Dosage on Renal Function: An Analysis of 8,548 Cardiac Surgical Patients Treated with Different Dosages of Aprotinin. Anesthesiology, 108, 189-198.
http://dx.doi.org/10.1097/01.anes.0000299428.55062.67
[20] Fergusson, D.A., Hébert, P.C., Mazer, C.D., Fremes, S., MacAdams, C., Murkin, J.M., Teoh, K., Duke, P.C., Arellano, R., Blajchman, M.A., Bussiéres, J.S., Côté, D., Karski, J., Martineau, R., Robblee, J.A., Rodger, M., Wells, G., Clinch, J. and Pretorius, R., BART Investigators (2008) A Comparison of Aprotinin and Lysine Analogues in High-Risk Cardiac Surgery. The New England Journal of Medicine, 358, 2319-2331.
http://dx.doi.org/10.1056/NEJMoa0802395
[21] Sedrakyan, A., Treasure, T. and Elefteriades, J.A. (2004) Effect of Aprotinin on Clinical Outcomes in Coronary Artery Bypass Graft Surgery: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. The Journal of Thoracic and Cardiovascular Surgery, 128, 442-448.
http://dx.doi.org/10.1016/j.jtcvs.2004.03.041
[22] Schloss, B., Gulati, P., Yu, L., Abdel-Rasoul, M., O’Brien, W., Von Visger, J. and Awad, H. (2011) Impact of Aprotinin and Renal Function on Mortality: A Retrospective Single Center Analysis. Journal of Cardiothoracic Surgery, 6, 103.
http://dx.doi.org/10.1186/1749-8090-6-103
[23] EPA (2013) Electronic Code of Federal Regulations, Title 40: Protection of Environment. PART 180 Tolerances and Exemptions for Pesticide Chemical Residues in Food. Subpart C: Specific Tolerances. Environmental Protection Agency, Washington DC.
[24] Just-Viera, J.O., Fischer, C.R., Gago, O. and Morris, J.D. (1984) Acute Reaction to Protamine. Its Importance to Surgeons. The American Surgeon, 50, 52-60.
[25] Holland, C.L., Singh, A.K., McMaster, P.R.B. and Fang, D.W. (1984) Adverse Reactions to Protamine Sulfate Following Cardiac Surgery. Clinical Cardiology, 7, 157-162.
http://dx.doi.org/10.1002/clc.4960070305
[26] Lee, H.L., Kan, C.D., Tsai, C.L., Liou, M.J. and Guo, H.R. (2009) Comparative Effects of the Formulation of Glyphosate-Surfactant Herbicides on Hemodynamics in Swine. Clinical Toxicology (Philadelphia), 47, 651-658.
http://dx.doi.org/10.1080/15563650903158862
[27] Lee, H.L., K.W., Chen, Chi, C.H., J.J., Huang and Tsai, L.M. (2000) Clinical Presentations and Prognostic Factors of a Glyphosate-Surfactant Herbicide Intoxication: A Review of 131 Cases. Academic Emergency Medicine, 7, 906-910.
http://dx.doi.org/10.1111/j.1553-2712.2000.tb02069.x
[28] Jayasumana, C., Gunatilake, S. and Senanayake, P. (2014) Glyphosate, Hard Water and Nephrotoxic Metals: Are They the Culprits behind the Epidemic of Chronic Kidney Disease of Unknown Etiology in Sri Lanka? International Journal of Environmental Research and Public, 11, 2125-2147.
http://dx.doi.org/10.3390/ijerph110202125
[29] Pandey, A. and Rudraiah, M. (2015) Analysis of Endocrine Disruption Effect of Roundup in Adrenal Gland of Male Rats. Toxicology Reports, 2, 1075-1085.
http://dx.doi.org/10.1016/j.toxrep.2015.07.021
[30] Livingston, M., Fernandez-Cornejo, J., Unger, J., Osteen, C., Schimmelpfennig, D., Park, T. and Lambert, D. (2015) The Economics of Glyphosate Resistance Management in Corn and Soybean Production. U.S. Department of Agriculture, Economic Research Service, April 2015, No. ERR-184.
[31] Benbrook, C.B. (2012) Impacts of Genetically Engineered Crops on Pesticide Use in the U.S.—The First Sixteen Years. Environmental Sciences Europe, 24, 2190-4715.
[32] Swanson, N.L., Leu, A., Abrahamson, J. and Wallet, B. (2014) Genetically Engineered Crops, Glyphosate and the Deterioration of Health in the United States of America. Journal of Organic Systems, 9, 6-37.
[33] Guyton, K.Z., Loomis, D., Grosse, Y., El Ghissassi, F., Benbrahim-Tallaa, L., Guha, N., Scoccianti, C., Mattock, H. and Straif, K., The International Agency for Research on Cancer Monograph Working Group (2015) Carcinogenicity of Tetrachlorvinphos, Parathion, Malathion, Diazinon, and Glyphosate. The Lancet Oncology, 16, 490-491.
http://dx.doi.org/10.1016/s1470-2045(15)70134-8
[34] Samsel, A. and Seneff, S. (2015) Glyphosate, Pathways to Modern Diseases IV: Cancer and Related Pathologies. The Journal of Biological Physics and Chemistry, 15, 121-159.
http://dx.doi.org/10.4024/11sa15r.jbpc.15.03
[35] Hazell, L. and Shakir, S.A. (2006) Under-Reporting of Adverse Drug Reactions: A Systematic Review. Drug Safety, 29, 385-396.
http://dx.doi.org/10.2165/00002018-200629050-00003
[36] Kristeller, J.L., Roslund, B.P. and Stahl, R.F. (2008) Benefits and Risks of Aprotinin Use during Cardiac Surgery. Pharmacotherapy, 28, 112-124.
http://dx.doi.org/10.1592/phco.28.1.112
[37] Linhardt, R.J. and Gunay, N.S. (1999) Production and Chemical Processing of Low Molecular Weight Heparins. Seminars in Thrombosis and Hemostasis, 3, 5-16.
[38] Cericato. L., Neto, J.G., Fagundes, M., Kreutz, L.C., Quevedo, R.M., Finco, J., da Rosa, J.G., Koakoski, G., Centenaro, L., Pottker, E., Anziliero, D. and Barcellos, L.J. (2008) Cortisol Response to Acute Stress in Jundi Rhamdiaquelen Acutely Exposed to Sub-Lethal Concentrations of Agrichemicals. Comparative Biochemistry and Physiology C-Toxicology & Pharmacology, 148, 281-286.
[39] Walsh, L.P., McCormick, C., Martin, C. and Stocco, D.M. (2000) Roundup Inhibits Steroidogenesis by Disrupting Steroidogenic Acute Regulatory (StAR) Protein Expression. Environmental Health Perspectives, 108, 769-776.
http://dx.doi.org/10.1289/ehp.00108769
[40] Johnson, E.O., Vlachoyiannopoulos, P.G., Skopouli, F.N., Tzioufas, A.G. and Moutsopoulos, H.M. (1998) Hypofunction of the Stress Axis in Sjögren’s Syndrome. The Journal of Rheumatology, 25, 1508-1514.
[41] Samsel, A. and Seneff, S. (2013) Glyphosate’s Suppression of Cytochrome P450 Enzymes and Amino Acid Biosynthesis by the Gut Microbiome: Pathways to Modern Diseases. Entropy, 15, 1416-1463.
http://dx.doi.org/10.3390/e15041416
[42] Mesnage, R., Arno, M., Costanzo, M., Malatesta, M., Séralini, G.-E. and Antoniou, M.N. (2015) Transcriptome Profile Analysis Reflects Rat Liver and Kidney Damage Following Chronic Ultra-Low Dose Roundup Exposure. Environmental Health, 14, 70.
http://dx.doi.org/10.1186/s12940-015-0056-1
[43] Séralini, G.-E., Clair, E., Mesnage, R., Gress, S., Defarge, N., Malatesta, M., Hennequin, D. and Spiroux de Vendômois, J. (2014) Republished Study: Long-Term Toxicity of a Roundup Herbicide and a Roundup-Tolerant Genetically Modified Maize. Environmental Sciences Europe, 26, 14.
http://dx.doi.org/10.1186/s12302-014-0014-5
[44] Walker, D.L. and Davis, M. (2002) The Role of Amygdala Glutamate Receptors in Fear Learning, Fear-Potentiated Startle and Extinction. Pharmacology Biochemistry and Behavior, 71, 379-392.
http://dx.doi.org/10.1016/s0091-3057(01)00698-0
[45] Falls, W.A., Miserendino, M.J. and Davis, M. (1992) Extinction of Fear-Potentiated Startle: Blockade by Infusion of an NMDA Antagonist into the Amygdala. The Journal of Neuroscience, 12, 854-863.
[46] Wilcox, K.S., Fitzsimonds, R.M., Johnson, B. and Dichter, M.A. (1996) Glycine Regulation of Synaptic NMDA Receptors in Hippocampal Neurons. Journal of Neurophysiology, 76, 3415-3424.
[47] Cattani, D., de Liz Oliveira Cavalli, V.L., Heinz Rieg, C.E., Domingues, J.T., Dal-Cim, T., Tasca, C.I., Mena Barreto Silva, F.R. and Zamoner, A. (2014) Mechanisms Underlying the Neurotoxicity Induced by Glyphosate-Based Herbicide in Immature Rat Hippocampus: Involvement of Glutamate Excitotoxicity. Toxicology, 320, 34-45.
http://dx.doi.org/10.1016/j.tox.2014.03.001
[48] Samsel, A. and Seneff, S. (2015) Glyphosate, Pathways to Modern Diseases III: Manganese Neurological Diseases, and Associated Pathologies. Surgical Neurology International, 6, 45.
[49] Bohrer, D., do Nascimento, P.C., Binotto, R. and Pomblum, S.C. (2001) Influence of the Glass Packing on the Contamination of Pharmaceutical Products by Aluminium. Part I: Salts, Glucose, Heparin and Albumin. Journal of Trace Elements in Medicine and Biology, 15, 95-101.
http://dx.doi.org/10.1016/S0946-672X(01)80050-X
[50] Seneff, S., Swanson, N. and Li, C. (2015) Aluminum and Glyphosate Can Synergistically Induce Pineal Gland Pathology: Connection to Gut Dysbiosis and Neurological Disease. Agricultural Science, 6, 42-70.
http://dx.doi.org/10.4236/as.2015.61005
[51] Alfrey, A.C. (1993) Aluminum Toxicity in Patients with Chronic Renal Failure. Therapeutic Drug Monitoring, 15, 593-597.
http://dx.doi.org/10.1097/00007691-199312000-00025
[52] Mayor, G.H., Sprague, S.M., Hourani, M.R. and Sanchez, T.V. (1980) Parathyroid Hormone-Mediated Aluminum Deposition and Egress in the Rat. Kidney International, 17, 40-44.
http://dx.doi.org/10.1038/ki.1980.5
[53] Cozzolino, M., Brancaccio, D., Gallieni, M., Galassi, A., Slatopolsky, E. and Dusso, A. (2005) Pathogenesis of Parathyroid Hyperplasia in Renal Failure. Journal of Nephrology, 18, 5-8.
[54] Sinha, P.K., Mandal, S. and Kundu, D. (2007) Leaching of Lead and Cadmium from Glass Dinnerware. Journal of Environmental Science and Engineering, 49, 58-61.
[55] Wanigasuriya, K.P., Peiris-John, R.J. and Wickremasinghe, R. (2011) Chronic Kidney Disease of Unknown Aetiology in Sri Lanka: Is Cadmium a Likely Cause? BMC Nephrology, 12, 32.
http://dx.doi.org/10.1186/1471-2369-12-32
[56] Sughis, M., Penders, J., Haufroid, V., Nemery, B. and Nawrot, T.S. (2011) Bone Resorption and Environmental Exposure to Cadmium in Children: A Cross-Sectional Study. Environmental Health, 10, 104.
http://dx.doi.org/10.1186/1476-069X-10-104
[57] Bawaskar, H.S., Bawaskara, P.H. and Bawaskara, P.H. (2010) Chronic Renal Failure Associated with Heavy Metal Contamination of Drinking Water: A Clinical Report from a Small Village in Maharashtra. Clinical Toxicology, 48, 768-769.
http://dx.doi.org/10.3109/15563650.2010.497763
[58] Mesnage, R., Bernay, B. and Séralini, G.-E. (2013) Ethoxylated Adjuvants of Glyphosate-Based Herbicides Are Active Principles of Human Cell Toxicity. Toxicology, 313, 122-128.
http://dx.doi.org/10.1016/j.tox.2012.09.006
[59] Mesnage, R., Defarge, N., Spiroux de Vendômois, J. and Séralini, G.-E. (2014) Major Pesticides Are More Toxic to Human Cells than Their Declared Active Principles. BioMed Research International, 2014, Article ID: 179691.
http://dx.doi.org/10.1155/2014/179691
[60] Moon, J.M. and Chun, B.J. (2010) Predicting Acute Complicated Glyphosate Eintoxication in the Emergency Department. Clinical Toxicology, 48, 718-724.
http://dx.doi.org/10.3109/15563650.2010.488640
[61] Roberts, D.M., Buckley, N.A., Mohamed, F., Eddleston, M.E., Goldstein, D.A., Mehrsheikh, A., Bleeke, M.S. and Dawson, A.H. (2010) A Prospective Observational Study of the Clinical Toxicology of Glyphosate-Containing Herbicides in Adults with Acute Self-Poisoning. Clinical Toxicology, 48, 129-136.
http://dx.doi.org/10.3109/15563650903476491
[62] Sato, C., Kamijo, Y., Yoshimura, K. and Ide, T. (2011) Aseptic Meningitis in Association with Glyphosate-Surfactant Herbicide Poisoning. Clinical Toxicology (Philadelphia), 49, 118-120.
http://dx.doi.org/10.3109/15563650.2011.552065
[63] Komuro, J., Kaneko, M., Ueda, K., Nitta, S., Kasao, M. and Shirai, T. (2015) Adrenal Insufficiency Causes Life-Threatening Arrhythmia with Prolongation of QT Interval. Heart and Vessels, Epub ahead of Print.
http://dx.doi.org/10.1007/s00380-015-0660-6
[64] Carter, G., Goss, A.N. and Doecke, C. (2005) Bisphosphonates and Avascular Necrosis of the Jaw: A Possible Association. Medical Journal of Australia, 182, 413-415.
[65] Bagan, J., Sáez, G.T., Tormos, M.C., Gavalda-Esteve, C., Bagan, L., Leopoldo-Rodado, M. and Camps, C. (2014) Oxidative Stress in Bisphosphonate-Related Osteonecrosis of the Jaws. Journal of Oral Pathology & Medicine, 43, 371-377.
http://dx.doi.org/10.1111/jop.12151
[66] Rodan, G.A. and Fleisch, H.A. (1996) Bisphosphonates: Mechanisms of Action. The Journal of Clinical Investigation, 97, 2692-2696.
http://dx.doi.org/10.1172/JCI118722
[67] De Roos, A.J., Blair, A., Rusiecki, J.A., Hoppin, J.A., Svec, M., Dosemeci, M., Sandler, D.P. and Alavanja, M.C. (2005) Cancer Incidence among Glyphosate-Exposed Pesticide Applicators in the Agricultural Health Study. Environmental Health Perspectives, 113, 49-54.
http://dx.doi.org/10.1289/ehp.7340
[68] Aman, J., van der Heijden, M., van Lingen, A., Girbes, A.R., van NieuwAmerongen, G.P., van Hinsbergh, V.W. and Groeneveld, A.B. (2011) Plasma Protein Levels Are Markers of Pulmonary Vascular Permeability and Degree of Lung Injury in Critically Ill Patients with or at Risk for Acute Lung Injury/Acute Respiratory Distress Syndrome. Critical Care Medicine, 39, 89-97.
http://dx.doi.org/10.1097/CCM.0b013e3181feb46a
[69] Jensen, J.S., Borch-Johnsen, K., Jensen, G. and Feldt-Rasmussen, B. (1995) Microalbuminuria Reflects a Generalized Transvascular Albumin Leakiness in Clinically Healthy Subjects. Clinical Science, 88, 629-633.
http://dx.doi.org/10.1042/cs0880629
[70] Sarafidis, P.A. and Bakris, G.L. (2006) Microalbuminuria and Chronic Kidney Disease as Risk Factors for Cardiovascular Disease. Nephrology Dialysis Transplantation, 21, 2366-2374.
http://dx.doi.org/10.1093/ndt/gfl309
[71] Meurman, J.H., Rantonen, P., Pajukoski, H. and Sulkava, R. (2002) Salivary Albumin and Other Constituents and Their Relation to Oral and General Health in the Elderly. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontology, 94, 432-438.
http://dx.doi.org/10.1067/moe.2002.122345
[72] Kamisawa, T., Tu, Y., Egawa, N., Sakaki, N., Inokuma, S. and Kamata, N. (2003) Salivary Gland Involvement in Chronic Pancreatitis of Various Etiologies. American Journal of Gastroenterology, 98, 323-326.
http://dx.doi.org/10.1111/j.1572-0241.2003.07230.x
[73] De Waele, J.J., Hoste, E.A.J., Baert, D., Hendricks, K., Rijckaert, D., Thibo, P., Van Biervliet, P., Blot, S.I. and Colardyn, F. (2007) Relative Adrenal Insufficiency in Patients with Acute Pancreatitis. Intensive Care Medicine, 33, 1754-1760.
http://dx.doi.org/10.1007/s00134-007-0747-3
[74] De Waele, J.J., Hoste, E., Decruyenaere, J. and Colardyn, F. (2003) Adrenal Insufficiency in Severe Acute Pancreatitis. Pancreas, 27, 244-246.
http://dx.doi.org/10.1097/00006676-200310000-00009
[75] Peng, Y.-S., Wu, C.-S., Chen, Y.-C., Lien, J.-M., Tian, Y.-C., Fang, J.-T., Yang, C., Chu, Y.-Y., Hung, C.-F., Yang, C.-W., Chen, P.-C. and Tsai, M.-H. (2009) Critical Illness-Related Corticosteroid Insufficiency in Patients with Severe Acute Biliary Pancreatitis: A Prospective Cohort Study. Critical Care, 13, R123.
http://dx.doi.org/10.1186/cc7978
[76] Yue, Y., Zhang, Y., Zhou, L., Qin, J. and Chen, X. (2008) In Vitro Study on the Binding of Herbicide Glyphosate to Human Serum Albumin by Optical Spectroscopy and Molecular Modeling. Journal of Photochemistry and Photobiology B, 90, 26-32.
http://dx.doi.org/10.1016/j.jphotobiol.2007.10.003
[77] Chen, P.O. and Mahler, J.F. (1992) NTP Technical Report on Toxicity Studies of Glyphosate (CAS No. 1071083-6) Administered in Dosed Feed to F344/N Rats and B6C3F1 Mice. National Toxicology Program, Research Triangle Park, NC, USA. NTP Toxicity Report Series No. 16, NIH Publication 92-3135, July 1992. Submitted to WHO by Monsanto In. Services SA, Brussels, Belgium.
[78] Glyphosate Renewal Assessment Report (RAR). Volume 3CA-CP B-6, Toxicology and Metabolism, 2013-12-18. Draft Report Submitted by Federal Institute for Risk Assessment (BfR, Germany) to the European Food Safety Authority. Last Accessed October 1, 2015.
http://www.scribd.com/doc/238089929/Glyphosate-RAR-08-Volume-3CA-CP-B-6-2013-12-18-San
[79] Hirota, M., Ohmuraya, M. and Baba, H. (2006) The Role of Trypsin, Trypsin Inhibitor, and Trypsin Receptor in the Onset and Aggravation of Pancreatitis. Journal of Gastroenterology, 41, 832-836.
http://dx.doi.org/10.1007/s00535-006-1874-2
[80] Malatesta, M., Caporaloni, C., Rossi, L., Battistelli, S., Rocchi, M.B., Tonucci, F. and Gazzanelli, G. (2002) Ultrastructural Analysis of Pancreatic Acinar Cells from Mice Fed on Genetically Modified Soybean. Journal of Anatomy, 201, 409-415.
http://dx.doi.org/10.1046/j.0021-8782.2002.00103.x
[81] Klimstra, D.S., Heffess, C.S., Oertel, J.E. and Rosai, J. (1992) Acinar Cell Carcinoma of the Pancreas: A Clinicopathologic Study of 28 Cases. The American Journal of Surgical Pathology, 16, 815-837.
http://dx.doi.org/10.1097/00000478-199209000-00001
[82] Salbego, J., Pretto, A., Machado da Silva, V.M., Loro, V.L., Lazzari, R., Gioda, C.R. and Baldisserotto, B. (2014) Glyphosate on Digestive Enzymes Activity in Piava (Leporinus obtusidens). Ciência Rural, 44, 1603-1607.
http://dx.doi.org/10.1590/0103-8478cr20131399
[83] Zouaoui, K., Dulaurent, S., Gaulier, J.M., Moesch, C. and Lachatre, G. (2013) Determination of Glyphosate and AMPA in Blood and Urine from Humans: About 13 Cases of Acute Intoxication. Forensic Science International, 226, e20-e25.
http://dx.doi.org/10.1016/j.forsciint.2012.12.010
[84] Kalra, A., Palaniswamy, C., Patel, R., Kalra, A. and Selvaraj, D.R. (2012) Acute Hypotensive Transfusion Reaction with Concomitant Use of Angiotensin-Converting Enzyme Inhibitors: A Case Report and Review of the Literature. American Journal of Therapeutics, 19, e90-e94.
http://dx.doi.org/10.1097/MJT.0b013e3181e4ddb2
[85] Raddy, M., Sriganesh, K., Bhadrinarayan, V. and Raghavendra, B.S. (2011) Unusual Manifestation of Blood Transfusion Reaction as Diffuse Operative Site Oozing, Hypotension and Brain Swelling. Journal of Anaesthesiology Clinical Pharmacology, 27, 130-131.
[86] Dumaswala, U.J., Zhuo, L., Jacobsen, D.W., Jain, S.K. and Sukalski, K.A. (1999) Protein and Lipid Oxidation of Banked Human Erythrocytes: Role of Glutathione. Free Radical Biology and Medicine, 27, 1041-1049.
http://dx.doi.org/10.1016/S0891-5849(99)00149-5
[87] Collard, K., White, D. and Copplestone, A. (2014) The Influence of Storage Age on Iron Status, Oxidative Stress and Antioxidant Protection in Paediatric Packed Cell Units. Blood Transfusion, 12, 210-219.
[88] Collard, K.J. and White, D.L. (2014) On the Source of the Non-Transferrin-Bound Iron Which Accumulates in Packed Red Blood Cell Units during Storage. Blood Transfusion, 12, 527-532.
[89] L’Acqua, C., Bandyopadhyay, S., Francis, R.O., McMahon, D.J., Nellis, M., Sheth, S., Kernie, S.G., Brittenham, G.M., Spitalnik, S.L. and Hod, E.A. (2015) Red Blood Cell Transfusion Is Associated with Increased Hemolysis and an Acute Phase Response in a Subset of Critically Ill Children. American Journal of Hematology, 90, 915-920.
http://dx.doi.org/10.1002/ajh.24119
[90] Cavas, T. and Könen, S. (2007) Detection of Cytogenetic and DNA Damage in Peripheral Erythrocytes of Goldfish (Carassius auratus) Exposed to a Glyphosate Formulation Using the Micronucleus Test and the Comet Assay. Mutagenesis, 22, 263-268.
http://dx.doi.org/10.1093/mutage/gem012
[91] Kwiatkowska, M., Huras, B. and Bukowska, B. (2014) The Effect of Metabolites and Impurities of Glyphosate on Human Erythrocytes (in Vitro). Pesticide Biochemistry and Physiology, 109, 34-43.
[92] Lu, W., Li, L., Chen, M., Zhou, Z., Zhang, W., Ping, S., Yan, Y., Wang, J. and Lin, M. (2013) Genome-Wide Transcriptional Responses of Escherichia coli to Glyphosate, a Potent Inhibitor of the Shikimate Pathway Enzyme 5-Enolpyruvylshikimate-3-Phosphate Synthase. Molecular BioSystems, 9, 522-530.
http://dx.doi.org/10.1039/c2mb25374g
[93] Lushchak, O.V., Kubrak, O.I., Storey, J.M., Storey, K.B. and Lushchak, V.I. (2009) Low Toxic Herbicide Roundup Induces Mild Oxidative Stress in Goldfish Tissues. Chemosphere, 76, 932-937.
http://dx.doi.org/10.1016/j.chemosphere.2009.04.045
[94] Benachour, N. and Séralini, G.-E. (2009) Glyphosate Formulations Induce Apoptosis and Necrosis in Human Umbilical, Embryonic and Placental Cells. Chemical Research in Toxicology, 22, 97-105.
http://dx.doi.org/10.1021/tx800218n
[95] Darbari, D.S., Kple-Faget, P., Kwagyan, J., Rana, S., Gordeuk, V.R. and Castro, O. (2006) Circumstances of Death in Adult Sickle Cell Disease Patients. American Journal of Hematology, 81, 858-863.
http://dx.doi.org/10.1002/ajh.20685
[96] Vichinsky, E.P., Haberkern, C.M., Neumayr, L., Earles, A.N., Black, D., Koshy, M., Pegelow, C., Abboud, M., Ohene-Frempong, K. and Iyer, R.V. (1995) A Comparison of Conservative and Aggressive Transfusion Regimens in the Perioperative Management of Sickle Cell Disease. The New England Journal of Medicine, 333, 206-213.
http://dx.doi.org/10.1056/NEJM199507273330402
[97] Ballas, S.K. (2001) Iron Overload Is a Determinant of Morbidity and Mortality in Adult Patients with Sickle Cell Disease. Seminars in Hematology, 38, 30-36.
[98] Platt, O.S., Brambilla, D.J., Rosse, W.F., Milner, P.F., Castro, O., Steinberg, M.H. and Klug, P.P. (1994) Mortality in Sickle Cell Disease. Life Expectancy and Risk Factors for Early Death. The New England Journal of Medicine, 330, 1639-1644.
http://dx.doi.org/10.1056/NEJM199406093302303
[99] Haynes Jr, J. and Allison, R.C. (1986) Pulmonary Edema: Complication in the Management of Sickle Cell Pain Crisis. American Journal of Medicine, 80, 833-840.
http://dx.doi.org/10.1016/0002-9343(86)90624-8
[100] Siddiqui, A.K. and Ahmed, S. (2003) Pulmonary Manifestations of Sickle Cell Disease. Postgraduate Medical Journal, 79, 384-390.
http://dx.doi.org/10.1136/pmj.79.933.384
[101] Shehata, A.A., Schrödl, W., Schledorn, P. and Krüger, M. (2014) Distribution of Glyphosate in Chicken Organs and Its Reduction by Humic Acid Supplementation. The Journal of Poultry Science, 51, 333-337.
http://dx.doi.org/10.2141/jpsa.0130169
[102] Ridley, W.P. and Mirly, K. (1988) The Metabolism of Glyphosate in Sprague-Dawley Rats-Part I. Excretion and Tissue Distribution of Glyphosate and Its Metabolites Following Intravenous and Oral Administration. (Unpublished Study MSL-7215 Conducted by Monsanto Company Environmental Health Laboratory and Submitted to the US EPA July 1988) MRID#407671-01.
[103] Horrow, J.C. (1988) Protamine Allergy. Journal of Cardiothoracic Anesthesia, 2, 225-242.
http://dx.doi.org/10.1016/0888-6296(88)90277-3
[104] Studier, F.W. (2005) Protein Production by Auto-Induction in High Density Shaking Cultures. Protein Expression and Purification, 41, 207-234.
http://dx.doi.org/10.1016/j.pep.2005.01.016
[105] Studier, F.W. (2014) Stable Expression Clones and Autoinduction for Protein Production in E. coli. Methods in Molecular Biology, 1091, 17-32.
http://dx.doi.org/10.1007/978-1-62703-691-7_2
[106] Filizadeh, Y. and Zolfinejad, K. (2011) Toxicity Determination on Three Sturgeon Species Exposed to the Glyphosate. Iranian Journal of Fisheries Sciences, 10, 383-392.
[107] Antón, F.A., Laborda, E. and Ariz, M. (1994) Acute Toxicity of the Herbicide Glyphosate Tofish. Chemosphere, 28, 745-753.
http://dx.doi.org/10.1016/0045-6535(94)90228-3
[108] Uotila, M., Gullner, G. and Kömives, T. (1995) Induction of Glutathione S-Transferase Activity and Glutathione Level in Plants Exposed to Glyphosate. Physiologia Plantarum, 93, 689-694.
[109] Basantani, M., Srivastava, A. and Sen, S. (2011) Elevated Antioxidant Response and Induction of Tau-Class Glutathione S-Transferase after Glyphosate Treatment in Vigna radiata (L.). Wilzek. Pesticide Biochemistry and Physiology, 99, 111-117.
http://dx.doi.org/10.1016/j.pestbp.2010.11.007
[110] Jain, M. and Bhalla-Sarin, N. (2001) Glyphosate-Induced Increase in Glutathione S-Transferase Activity and Glutathione Content in Groundnut (Arachis hypogaea L.). Pesticide Biochemistry and Physiology, 69, 142-152.
http://dx.doi.org/10.1006/pest.2000.2535
[111] Lee, D.H. and Jacobs, D.R. (2009) Is Serum Gamma-Glutamyltransferase an Exposure Marker of Xenobiotics? Empirical Evidence with Polycylic Aromatic Hydrocarbon. Clinical Chemistry and Laboratory Medicine, 47, 860-862.
http://dx.doi.org/10.1515/CCLM.2009.197
[112] Lum, G. and Gambino, S.R. (1972) Serum Gamma-Glutamytranspeptidase Activity as an Indicator of Disease of Liver, Pancreas, or Bone. Clinical Chemistry, 18, 358-362.
[113] Lum, G. (1974) Gamma-Glutamyl Transpeptidase in Cancer Diagnosis. Annals of Clinical & Laboratory Science, 4, 13-18.
[114] Miyazaki, S. and Okumura, M. (1992) Change of Serum Glutamyltranspeptidase Level and Isoenzyme Pattern in Hepatobiliary Pancreatic Disease. Clinica Chimica Acta, 40, 193-197.
[115] Mastellone, V., Tudisco, R., Monastra, G., Pero, M.E., Calabrò, S., Lombardi, P., Grossi, M., Cutrignelli, M.I., Avallone, L. and Infascelli, F. (2013) Gamma-Glutamyltransferase Activity in Kids Born from Goats Fed Genetically Modified Soybean. Food and Nutrition Sciences, 4, 50-54.
http://dx.doi.org/10.4236/fns.2013.46A006
[116] Khorana, A.A., Francis, C.W., Blumberg, N., Culakova, E., Refaai, M.A. and Lyman, G.H. (2008) Blood Transfusions, Thrombosis and Mortality in Hospitalized Patients with Cancer. Archives of Internal Medicine, 168, 2377-2381.
http://dx.doi.org/10.1001/archinte.168.21.2377
[117] Zacharski, L.R. (2005) Hypercoagulability Preceding Cancer. The Iron Hypothesis. Journal of Thrombosis and Haemostasis, 3, 585-588.
http://dx.doi.org/10.1111/j.1538-7836.2005.01178.x
[118] Dominici, S., Paolicchi, A., Lorenzini, E., Maellaro, E., Comporti, M., Pieri, L., Minotti, G. and Pompella, A. (2003) Gamma-Glutamyltransferase-Dependent Prooxidant Reactions: A Factor in Multiple Processes. Biofactors, 17, 187-198.
[119] Koenig, G. and Seneff, S. (2015). Gamma-Glutamyltransferase: A Predictive Biomarker of Cellular Antioxidant Inadequacy and Disease Risk. Disease Markers, 2015, Article ID: 818570.
http://dx.doi.org/10.1155/2015/818570
[120] Falhammar, H., Filipsson, H., Holmdahl, G., Janson, P.-O., Nordenskjöld, A., Hagenfeldt, K. and Thorén, M. (2009) Increased Liver Enzymes in Adult Women with Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency. Endocrine Journal, 56, 601-608.
http://dx.doi.org/10.1507/endocrj.K08E-312
[121] Patak, P., Willenberg, H.S. and Bornstein, S.R. (2004) Vitamin C Is an Important Cofactor for Both Adrenal Cortex and Adrenal Medulla. Endocrine Research, 30, 871-875.
http://dx.doi.org/10.1081/erc-200044126
[122] Song, J.H., Simons, C., Cao, L., Shin, S.H., Hong, M. and Chung, I.M. (2003) Rapid Uptake of Oxidized Ascorbate Induces Loss of Cellular Glutathione and Oxidative Stress in Liver Slices. Experimental & Molecular Medicine, 35, 67-75.
http://dx.doi.org/10.1038/emm.2003.10
[123] Olabisi, A.O. (2005) The Chemistry of L-Ascorbic acid Derivatives in the Asymmetric Synthesis of C2- and C3-Substituted Aldonolactones. Ph.D. Dissertation, College of Liberal Arts and Sciences, Wichita State University, Wichita.
[124] Hsiao, C.T., Lin, LJ., Hsiao, K.Y., Chou, M.H. and Hsiao, S.H. (2008) Acute Pancreatitis Caused by Severe Glyphosate-Surfactant Oral Intoxication. The American Journal of Emergency Medicine, 26, 384.e3-384.e5.
http://dx.doi.org/10.1016/j.ajem.2007.06.024
[125] Garcia-Szabo, R.R. and Malik, A.B. (1984) Pancreatitis-Induced Increase in Lung Vascular Permeability. Protective Effect of Trasylol. American Review of Respiratory Disease, 129, 580-583.
[126] Mao, Y. and Kunapuli, S.P. (2013) Trypsin Causes Platelet Activation Independently of Known Protease-Activated Receptors. Thrombosis and Haemostasis, 110, 1241-1249.
http://dx.doi.org/10.1160/th13-03-0189
[127] Bradshaw, M., Mansfield, A. and Peikert, T. (2013) The Role of Vascular Endothelial Growth Factor in the Pathogenesis, Diagnosis and Treatment of Malignant Pleural Effusion. Current Oncology Reports, 15, 207-216.
http://dx.doi.org/10.1007/s11912-013-0315-7
[128] Martin, S., Maruta, K., Burkart, V., Gillis, S. and Kolb, H. (1988) IL-1 and IFN-Gamma Increase Vascular Permeability. Immunology, 64, 301-305.
[129] Tahamont, M.V., Barie, P.S., Blumenstock, F.A., Hussain, M.H. and Malik, A.B. (1982) Increased Lung Vascular Permeability after Pancreatitis and Trypsin Infusion. The American Journal of Pathology, 109, 15-26.
[130] Hartmann, J.R., Robinson, J.A. and Gunnar, R.M. (1977) Chemotactic Activity in the Coronary Sinus after Experimental Myocardial Infarction: Effects of Pharmacologic interventions on Ischemic Injury. American Journal of Cardiology, 40, 550-555.
http://dx.doi.org/10.1016/0002-9149(77)90070-4
[131] Roxvall, L., Sennerby, L., Johansson, B.R. and Heideman, M. (1990) Trypsin-Induced Vascular Permeability and Leukocyte Accumulation in Hamster Cheek Pouch: The Role of Complement Activation. Journal of Surgical Research, 49, 504-513.
http://dx.doi.org/10.1016/0022-4804(90)90175-2
[132] Loh, Y.P. and Gainer, H. (1980) Evidence That Glycosylation of Pro-Opiocortin and ACTH Influences Their Proteolysis by Trypsin and Blood Proteases. Molecular and Cellular Endocrinology, 20, 35-44.
http://dx.doi.org/10.1016/0303-7207(80)90092-1
[133] Sakaeda, T., Tamon, A., Kadoyama, K. and Okuno, Y. (2013) Data Mining of the Public Version of the FDA Adverse Event Reporting System. International Journal of Medical Sciences, 10, 796-803.
http://dx.doi.org/10.7150/ijms.6048

Copyright © 2023 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.