Protection against the toxic effects of the favism factor (divicine) in rats by vitamins E, A and C and iron chelating agents

Abstract

AbstractFive experiments were carried out with weanling Sprague‐Dawley rats to determine if prior administration of either free‐radical scavenging compounds (vitamins A, C and E) or chelating agents (EDTA and desferox‐ amine) affected the toxicity of divicine (DV). In all experiments, intraperitoneal (IP) injections of 250 mg g−1 body weight of DV alone resulted in 100% mortalities within 24 h with most of the deaths occurring before 4 h. Death was accompanied by a rapid decrease in the concentration of glutathione (GSH) in the red blood cells (RBC) and the 576 nm/628 nm absorbance ratio of haemoglobin. The first experiment demonstrated that IP injections of different amounts of vitamin E, 1 h prior to DV injection, prevented the decrease in the haemoglobin absorbancy ratio and GSH concentration and greatly reduced mortalities. In rats that received 1000 IU of vitamin E kg−1 body weight prior to DV injection, mortality was only 20%. The second experiment demonstrated that the optimal time for IP administration of vitamin E was 1 to 4 h prior to DV injection although some protection was obtained after 96 h. In contrast, the optimal time for intramuscular injections was 24 h prior to DV administration. A dosage of 250 or 500 IU of vitamin E kg−1 body weight provided complete protection (zero mortalities) against the toxic effects of DV. In the third experiment, the addition of varying amounts of vitamin E to the diet resulted in a dose dependent mortality curve with no deaths occurring in rats fed diets containing the highest concentrations of vitamin E. The fourth experiment also demonstrated that vitamin A, vitamin C, EDTA and desferoxamine each protected rats to varying degrees against the toxic effets of DV. In the final experiment it appeared that the combined injections of a free‐radical scavenging compound (vitamin E) and a metal chelator (desferoxamine) provide more protection than vitamin E alone. These results demonstrate for the first time in vivo that certain vitamins, especially vitamin E, and metal chelators can provide varying and in some cases 100% protection against the toxic effects DV.