Annual Meeting of the Japanese Society of Toxicology

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The knowledge about toxicity of Abrus precatorius seed is ubiquitous. However there is need to define the toxicity limit of Abrus precatorius leaf in monogastric animals. Therapeutic animal-human and human-animal equivalent doses were determined using human equivalent dose formular. Human Equivalent Dose (HED) is equal to animal dose multiplied by animal km factor divided by human K_m factor. Whereas K_m factor is body weight (kg) divided by body surface area (m²). Human Equivalent No-observable Adverse Effects Dose is equal to animal no-observable adverse effect level (NOAEL) multiplied by animal weight (Wa) divided by human weight (Wh) rest to the power of 0.33 was used to confirm 12.5mg/kg body weight of mice (relatively safe dose) translated to human and other animal’s safe doses. The LD₅₀ of aqueous leaf extract of Abrus precatorius in mice was estimated to be 2559.5 to 3123.3mg/kg body weight. Whereas the LD₅₀extrapolated from mouse to rat (1349.3-1646.6mg/kg), hamster (1855.3-2264.1mg/kg), guinea pig (1279.5-1561.4mg/kg), rabbit (618.4-754.7mg/kg), monkey (593.7-724.5mg/kg), cat (392.7-479.2mg/kg), dog and baboon (371.1-452.8mg/kg), child (297-362mg/kg) and adult human (197.8-241.5mg/kg) body weight respectively could be a reality. The therapeutic safe dose range for the animals was 1-12.5mg/kg body weight for a period of 7 days, but at dose ≤ 200mg/kg bodyweight the leaf extract have haematonic effect. However, at higher dose > 200mg/kg, the extract showed haemolytic activity in rat, whereas at dose ≥ 25.0mg/kg. The leaf extract might be organotoxic to monogastric animals.

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Generically, carcinogenic effects of chemicals in bladder carcinogenesis are judged by papillary or nodular (PN) hyperplasia induction in rats given N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) for four weeks and the test chemicals for 22-28 weeks. However, up-regulation of vascular endothelial growth factor (VEGF) begins early in rat BBN bladder carcinogenesis. To establish a short term rat bladder carcinogenic bioassay, we analyzed the correlation of VEGF, VEGF mRNA and bladder lesions inductions between 10 and 26 weeks after BBN treatment. Six-week-old male Wistar (slc) rats were given 0.05% BBN for 4, 10 or 26 weeks. To avoid individual rat bias, the bladders were investigated by partial cystectomy at 10 weeks and total cystectomy at 26 weeks. After induction, PN hyperplasia and carcinoma in rats increased with length of BBN treatment and immunohistochemical VEGF expression also increased following carcinogenesis, but immunoreactivity of individual lesions was quite variable. Moreover, induction of PN hyperplasia at 10 weeks BBN treatment was not significantly correlation with that of 26 weeks treatment; then, it was impossible to predict the carcinogenic effect by the induction of PN hyperplasia at 26 weeks BBN treatment by that at 10 weeks BBN treatment. However, VEGF mRNA levels of rat bladders at 10 weeks BBN treatment revealed a strong significant correlation with the incidence of bladder lesions at 26 weeks treatment. Here, we suggest the quantitative VEGF mRNA levels are a good biomarker for short-term BBN induced rat bladder carcinogenesis bioassay.

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