Abstract
Objective(s): Newer organo-metallic, specifically gold (III) complexes with multiple ligands are currently being formulated with primary focus of having increased anti-cancerous properties and decreased cytotoxicity. In this study, histological toxicity profile of a newly formulated anti-cancerous gold (III) compound [trans-(+/-)-1,2-(DACH)2Au]Cl3 Bis(trans-1,2-Diaminocyclohexane) was investigated by evaluation of kidney and liver tissues of treated rats.
Materials and Methods: This is a quasi-experimental study. In acute toxicity component of the study, (n = 16) male rats weighing between 200-250 g were administered single, variable concentration of the gold (III) compound, [trans-(+/-)-1,2-(DACH)2Au]Cl3 Bis(trans-1,2-Diaminocyclohexane) to determine LD50 (dose that is lethal to 50% of rats). An IP injection of 2.3 mg/kg (equivalent to 1/10 of LD50) was injected for 14 consecutive days to (n=10) male rats in the sub-acute component of the study. Autopsy preservation of liver and kidney tissue in buffered formalin, sample processing, histopathological evaluation, and comparison with unremarkable controls (n=5) was conducted sequentially.
Results: A dose of 2.3 mg/kg did not produce any tubular necrosis in kidney specimens. Mild interstitial inflammation with prominence of plasma cells was the main histological alteration. Plasmacytic pyelitis was also seen. Varying extents of cytoplasmic vacuolization and mild focal lobular and portal inflammation were predominant hepatic microscopic findings.
Conclusion: [trans-(+/-)-1,2-(DACH)2Au]Cl3 Bis(trans-1,2-Diaminocyclohexane) produced no histological damage in renal and hepatic tissues of rats. This very limited sample animal-based study points to the relative safety of this new gold compound. However, there is a need to compare this compound with established drugs in a comparative non-animal based study.