Effect of Disulfiram/Copper Gluconate Combination on Haematological Indices in Rodents


The chronic toxicological profile of disulfiram/copper gluconate (DSF/CG) combination was investigated in a 90 day time and dose dependent study. A total of 148 rats weighing 260 - 300 g were used for this study; 60 for the pilot study and 88 for the chronic toxicity test. 88 rats divided into eleven groups consisting of 8 rats each were used for the main experiment. Groups 1 and 2 served as control groups and received normal saline as placebo and 99.5% dimethyl sulfoxide (DMSO) (Solvent control), respectively. Drugs were administered orally via a 1 ml syringe. Animals were given three doses (1/5th, 1/10th and 1/20th) of the calculated LD50 of 373 mg/kg and 75 mg/kg for disulfiram and copper gluconate respectively. Dosing was done daily with that of the combination given 12 hours apart. Blood samples were obtained via cardiac puncture on days 30, 45, 60 and 90 for analysis. Haematological parameters showed a significant (p < 0.05) dose- and time-dependent decrease in the packed cell volume, red blood cell count, white blood cell count and platelet count respectively. The results indicate bone marrow depression evidenced by anemia, leucopenia and thrombocytopenia in the experimental animals. The DSF/CG combination appears to exhibit a synergistic dose-dependent haematotoxicity.

Share and Cite:

Owunari, G. , Minakiri, S. and Wolfe, O. (2015) Effect of Disulfiram/Copper Gluconate Combination on Haematological Indices in Rodents. Pharmacology & Pharmacy, 6, 17-24. doi: 10.4236/pp.2015.61003.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Chen, S.H., Liu, S.H., Liang, Y.C., Lin, J.K. and Lin-Shiau, S.Y. (2001) Oxidative Stress and c-Junamino-Terminal Kinase Activation Involved in Apoptosis of Primary Astrocytes Induced by Disulfiram-Cu21 Complex. European Journal of Pharmacology, 414, 177-188.
[2] Cen, D., Gonzalez, R.I., Buckmeier, J.A., Kahlon, R.S., Tohidian, N.B. and Meyskens Jr., F.L. (2002) Disulfiram Induces Apoptosis in Human Melanoma Cells: A Redox-Related Process. Molecular Cancer Therapeutics, 1, 197-204.
[3] Daniel, K.G., Chen, D., Yan, B. and Dou, Q.P. (2007) Copper-Binding Compounds as Proteasome Inhibitors and Apoptosis Inducers in Human Cancer. Frontiers in Bioscience, 12, 135-144.
[4] Gupte, A. and Mumper, J. (2009) Elevated Copper and Oxidative Stress in Cancer Cells as a Target for Cancer Treatment. Cancer Treatment Reviews, 35, 32-46.
[5] Chen, D., Cui, Q.C., Yang, H. and Dou, Q.P. (2006) Disulfiram, a Clinically Used Anti-Alcoholism Drug and Copper-Binding Agent, Induces Apoptotic Cell Death in Breast Cancer Cultures and Xenograftsvia Inhibition of the Proteasome Activity. Cancer Research, 66, 10425-10433.
[6] Patel, S. (2004) Demonstration of Karber’s Method of LD50 Determination. Journal of Chemical Pharmaceutical Research.
[7] Grossmann, K.F., Blankenship, M.B., Akerley, W., Terrazas, M.C., Kosak, K.M., Boucher, K.M., Buys, S.S., Jones, K., Werner, T.L., Agarwal, N., Weis, J., Sharma, S., Ward, J. and Shami, P.J. (2011) Abstract 1308: A Phase I Clinical Study Investigat-ing Disulfiram and Copper Gluconate in Patients with Advanced Treatment-Refractory Solid Tumors Involving the Liver. Cancer Research, 71.
[8] Al-Naimi, R.A., Al-Tayar, N.H., Alsoufi, L.A.M. and Al-Taae, E.H.Y. (2013) Hematological and Biochemical Evaluation after Different Orally Doses of Copper Sulfate in Rats. The Iraqi Journal of Veterinary Medicine, 38, 83-91.
[9] Adams, K.F., Johnson, G., Hornowski, K.E. and Lineberger, T.H. (1979) The Effect of Copper on Erythrocytes Deformability: A Possible Mechanism of Hemolysis in Acute Copper Intoxication. 23. Biochimica et Biophysica Acta, 550, 279-287.
[10] Adam, S.E.I. and Wasfi, I.A. (1977) Chronic Copper Toxicity in Nubain Goats. Journal of Comparative Pathology, 87, 623-627.
[11] Ralph, A. and McArdle, H.J. (2001) Copper Metabolism and Requirements in the Pregnant Mother, Her Fetus, and Children. International Copper Association, New York.
[12] International Programme on Chemical Safety (1998) Environmental Health Criteria No. 200: Copper. World Health Organization, Geneva.
[13] Bedard, K., Fuentealba, I.C. and Cribb, A. (2000) The Long Evans Cinnamon (LEC) Rat Develops Hepatocellular Damage in the Absence of Antimicrosomal Antibodies. Toxicology, 146, 101-109.
[14] Turnlund, J.R., Jacob, R.A., Keen, C.L., et al. (2004) Long-Term High Copper Intake: Effects on Indexes of Copper Status, Antioxidant Status, and Immune Function in Young Men. The American Journal of Clinical Nutrition, 79, 1037-1044.

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.