Abstract
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.
Highlights
Disulfiram (Antabuse) (Figure 1), a drug used for the aversive therapy of alcoholism and copper gluconate are being repurposed for cancer chemotherapy
Disulfiram-induced cytotoxicity has been reported to be mediated by oxidative stress [1] [2], and this may be enhanced by the presence of copper [1]
148 Albino Swiss rats of both sexes weighing between 260 g - 300 g obtained from the Department of Pharmacology animal house were used for this study. 88 rats were used for the main experiment while 60 rats were used for the pilot study
Summary
Disulfiram (Antabuse) (Figure 1), a drug used for the aversive therapy of alcoholism and copper gluconate are being repurposed for cancer chemotherapy. (2015) Effect of Disulfiram/Copper Gluconate Combination on Haematological Indices in Rodents. Disulfiram-induced cytotoxicity has been reported to be mediated by oxidative stress [1] [2], and this may be enhanced by the presence of copper [1]. Copper binding drugs inhibit proteasome activity [3] and generate reactive oxygen species (ROS) [4]. Researchers have observed that in the presence of copper, disulfiram exhibits cytotoxic effects on a number of cancer cell lines. It is postulated that disulfiram, chemically a bis-N, N-diethyldithiocarbamate forms a carbamato complex with copper II ions in situ which inhibits the proteasome activity, instigating apoptosis and eventual cell death [5]. This research work set out to study the chronic toxicological effect of the DSF/CG combination on haematological parameters in rodents
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