Abrin lethality

Eiklid, K., Olsnes, S., and Pihl, A. (1980) Entry of lethal doses of abrin, ricin, and modeccin into the cytosol of Hela cells. Exp. Cell Res. 126, 321-326. 

Human parenteral toxicity for abrin is approximately 0.1-1 Jig/kg (Romano et al, 2007). However, based on clinical trials on abrin-immunotoxin use for cancer treatment, the human minimum lethal dose by intravenous injection was estimated to be >0.3 Jig/kg without occurrence of serious adverse effects (Gill, 1982). 

Interestingly, the hope for a vaeeination in the treatment against abrin toxieity may be not that far away. In a reeent in vitro and in vivo study, antibodies speeifie to the reeombi-nant abrin A-ehain were shown to reseue eells from toxieity. Importantly, the antibody also proteeted miee from lethal doses of the toxin. The neutralizing effeet of the antibody... 

Funatsu, G., Funatsu, M. (1970). Isolation and chemical properties of various types of ricin. Jpn. J. Med. Sci. Biol. 23 342-4 Gareth, D., Griffiths, G.D., Rice, P., Allenby, A.C., Bailey, S.C., Upshall, D.G. (1995). Inhalation toxicology and histopa-thology of ricin and abrin toxins. Inhal. Toxicol. 7 269-88 Gill, D.M. (1982). Bacterial toxins a table of lethal amounts. Microbiol. Rev. 46 86-94. 

Abrin is a plant source Type 2 RIP. It is found in Abrus precatorius (rosary pea, Indian licorice, jequirity bean). The toxicology of abrin is considered to be very similar to ricin. A similar Abrus toxin is pulchellin, produced by A. pul-chellus (Millard and LeClaire, 2008). The rosary pea has been reported to be more toxic than castor beans (Griffiths et al, 1994). Species sensitivity is variable and horses are considered to be the most sensitive. The mature goat is considered to be a more resistant species and 2 g of seed/kg body weight is reported as a lethal dose. The lethal dose for cattle is reported at 600 mg of seed/kg body weight. It is likely that abrin is denatured in the rumen (Burrows and Tyrl, 2001). 

Ricin and related type 2 RIP plant toxins are comparably lethal to laboratory mice under controlled conditions (Table 17.3). Variations in the LD50 values for a single toxin reported by different laboratories are comparable with variations among different toxins. Few controlled animal studies are available for several of these toxins, and comparisons among laboratories are limited by differences in toxin preparations, animal strains, and methodologies employed. The postexposure observation period is a particularly important variable for example, the literature values for the acute toxicity of abrin vary by 80-fold depending on whether intoxicated animals are observed for 24 or 48 h after exposure (Dickers et al., 2003). 

There are likely differences among species in susceptibility to related plant toxins but, as with ricin, these are often obscured by interlaboratory variability. In one comparative study of abrin (i.v.) lethality in different animals, the MED for mice was 10-fold greater (0.7 pg/kg) than that for rabbits (0.03-0.06 pg/kg), with rats and guinea pigs showing intermediate sensitivity (Fodstad et al., 1979) these findings parallel those for ricin (Table 17.2). 

Likewise, a formalin-treated abrin toxoid vaccine was shown to reduce lethality in rats exposed to a supralethal aerosol challenge with toxin the abrin toxoid delayed the onset of pulmonary toxicity, but could not prevent significant lung damage (Griffiths et al., 1995b). 

The human minimum lethal dose of abrin by intravenous injection is more than 0.3 pg/kg (Gill, 1982) since in clinical trials, patients have tolerated this dose without serious adverse effects. 

Intraperitoneal injection in mice caused anorexia, drowsiness and diminished then absent reflexes (el-Shabrawy et al., 1987). Guinea-pigs given intraperitoneal abrus seed extract showed similar features (Routh and Lahiri, 1971). The intraperitoneal dose which was lethal to 50% (LD50) of treated mice has variably been reported as 8.34 mg/kg (el-Shabrawy et al., 1987) and 0.02 mg/kg (Lin et al., 1969). This discrepency is likely to reflect differences in purity of the abrin extract and/or experimental conditions. 

Improved survival after a lethal dose of abrin has also been claimed with ascorbic acid pretreatment for 48 h prior to abrin administration (Clark et al., 1981). However, the benefit was completely lost if ascorbate administration occured 15 min or more after abrin exposure, again limiting any clinical application. 

Ricin is most toxic when inhaled and is therefore a potential aerosol threat. However, large quantities would he needed to cause toxicity. Ricin is much less lethal when ingested, suggesting poor absorption. The toxicity and lethality of parenteral exposure to ricin are well documented. Abrin which is closely related to ricin in structure is extremely toxic with an LD50 dose for humans of 2 pg/kg. 

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