Subacute Toxicity of Pentavalent Antimony Compounds in Rats

Abstract

A subacute toxicity study of pentavalent antimony (Sb) compounds, sodium stibogluconate (SSG) and meglumine antimoniate (MA) was carried out in rats. Three groups of 10 rats each were treated with saline (control group), 300 mg Sb kg-1 d-1 or 900 mg Sb kg-1 d-1 of SSG for 30 d. A parallel study of similar type was conducted for MA. Compared with controls, drug-treated rats showed an impairment of feeding habits and retardation of weight gain ( P < 0.01) during the treatment period. In both SSG- and MA-treated rats there was a dose-related reduction in haemoglobin concentration ( P < 0.001), and hematocrit ( P < 0.001). Red cell count was reduced in SSG-treated rats only. Both drugs, however, significantly raised the white cell count ( P < 0.05). These changes were more pronounced with SSG them with MA. There was no change in MCV, MCH and MCHC. SSG, 900 mg Sb kg-1 d-1, significantly raised AST ( P < 0.005), ALT ( P < 0.01) and alkaline phosphatase activity (P < 0.01). SSG-treated rats also had raised BUN ( P < 0.01) and creatinine ( P < 0.001), but no significant change in bilirubin levels. MA significantly raised AST ( P < 0.01), ALT ( P < 0.01), BUN ( P < 0.001) and serum creatinine levels (P < 0.001), but had no appreciable effect on bilirubin and alkaline phosphatase levels. Both SSG and MA decreased blood glucose levels ( P < 0.01) and induced proteinuria. It is concluded that the pentavalent antimony compounds (SSG and MA) retard growth rate and cause hepatotoxicity, nephrotoxicity and haematological abnormalities. The range and severity of toxicity, however, vary with the preparation and the dose.