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.