Abstract
This research work investigated and compared the chronic renal toxicological profile of disulfiram, copper gluconate and disulfiram/copper gluconate combination, in a 90-day time- and dose-dependent study in rodents. 88 rats weighing an average of 280 g divided into eleven groups consisting of 8 rats each were used for this experiment. The control groups received normal saline as placebo and 99.5% dimethyl sulfoxide (DMSO) (solvent control). Three oral doses (low, medium and high) of disulfiram (18.65 mg/kg, 37.3 mg/kg and 74.6 mg/kg), copper gluconate (3.75 mg/kg, 7.5 mg/kg and 15 mg/kg) and both drugs in combination were administered daily with those of the combination given 12 hours apart. Blood samples were collected via cardiac puncture in heparinised bottles and centrifuged, and the serum was decanted on 30, 45, 60 and 90 days for analysis. Renal function parameters—electrolytes (Na+, K+), urea and creatinine were evaluated. Results showed significant (p < 0.05) dose- and time-dependent increase in electrolyte level (Na+, K+), blood urea and creatinine respectively. The results are all pointers to the development of renal failure. It therefore appears that the DSF/CG combination is nephrotoxic and this effect is dose-dependent and synergistic.
Highlights
Cancer, termed malignant tumour or neoplasm, is a group of diseases involving abnormal cell growth with a potential to invade or spread to other parts of the body
Results of the present study revealed that low dose disulfiram, copper gluconate and disulfiram/copper gluconate combination revealed significantly increased (p < 0.05) sodium ion levels (Table 1)
At the medium and high doses, our results revealed significant increase (p < 0.05) for disulfiram alone, copper gluconate alone and the disulfiram and copper gluconate combination when compared with the control (Table 8 and Table 9)
Summary
Termed malignant tumour or neoplasm, is a group of diseases involving abnormal cell growth with a potential to invade or spread to other parts of the body. Researchers attest to the fact that individuals in this region are at increasing risk of developing cancers as a result of oil exploration activities [2]. This underscores the interest of the researchers in new drug treatment for cancers that would be readily available to low-income economies and affordable. Repurposing disulfiram has recently become of interest because of its pre-clinically described anti-cancer effects against various human cancers, which include breast, cervical, colorectal, lung, melanoma, prostate as well as myeloma and leukaemia [6] [7]. In a study on ovarian cancer cell lines, Papaioannou et al [15] reported that when cell lines were tested using disulfiram alone and disulfiram with copper supplementation, disulfiram alone reduced cell survival of ovarian cancer cells at an optimum concentration even in the absence of copper supplementation, but supplementation with 1 μM copper chloride, increased the cytotoxic effect of disulfiram in all other ovarian cancer cells tested
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