Favism‐like effects of divicine and isouramil in the rat: Acute and chronic effects on animal health, mortalities, blood parameters and ability to exchange respiratory gases

Abstract

AbstractIn vivo and in vitro experiments were carried out to establish the effects of divicine (DV) and isouramil (IU) on the rat when administered intra‐peritoneally (IP). The LD50for DV and IU was 148 and 183 mg kg−1 body weight, respectively. There was a high negative correlation between the amount of DV added in vitro to blood and the blood glutathione (GSH) concentration, the hemoglobin absorbance ratio (576 nm/630 nm) and the erythrocyte sedimentation rate. The same relationships occurred in vivo, with mortalities also being highly correlated with these factors. Intravenously injected DV completely disappeared from the blood within a few minutes, indicating a very short half‐life. The concentration of glutathione (GSH) in the red blood cells (RBC) was much higher and affected to a much greater degree in vivo by D V compared with GSH in the plasma. In the fourth experiment successive sub acute injections of DV and IU increased spleen weight and adrenal weights (IU only) and reduced kidney weights. Packed cell volume, hemoglobin concentration, leucocytes, lymphocytes, monocytes, and urea‐N were also affected. Blood gas analyses in the fifth study showed that both DV and IU markedly reduced the partial pressure of oxygen in the blood, the per cent oxygen saturation, the pH and the bicarbonate concentration. This suggests that these compounds impaired the functional capacity of the RBC. The concentration of GSH was lower in RBC from young rats, and young rats, as compared with more mature rats, were considerably more sensitive to the toxic effects of DV. This work provides direct evidence, for the first time, on many of the adverse effects of these compounds.