Journal of natural toxins最新文献

Cobrotoxin is the main neurotoxic protein isolated from the venom of Taiwan cobra Naja naja atra. It is a small, basic protein consisting of a single polypeptide chain of 62 amino acids, cross-linked by four disulfide bonds. The disulfide bonds and Tyr-25 which is buried in the molecule form a central core to maintain and stabilize the active conformation of the toxin. Selective and stepwise chemical modifications of cobrotoxin indicate that at least two cationic groups, an epsilon-amino group of Lys-47 and a guanidino group of Arg-33, both of which are common to all known postsynaptic neurotoxins, held at a certain critical distance in the molecule, are functionally important for its neuromuscular blocking activity. The cDNA encoding cobrotoxin was constructed from the cellular RNA isolated from the venom glands of Naja naja atra by reverse transcription polymerase chain reaction. Sequencing several clones containing about 0.5 Kb DNA inserts contained a complete and full-length reading frame of 249 base pairs covering a precursor of cobrotoxin gene with a deduced mature protein sequence of 62 amino acids which are identical to the amino acid sequence of cobrotoxin and a 21 amino acid segment of signal peptide. Expression of cobrotoxin in E. coli vector generated a polypeptide which can cross-react with the antisera against the native cobrotoxin.

Genus Vibrio includes some pathogenic species which are classified into two groups: a gastrointestinal infection group and an extraintestinal infection group. The vibrios produce various toxic proteins. Cholera toxin (CT) produced by V. cholerae O1 and O139 is a factor causing diarrhea with severe dehydration by ADP-ribosylation of the alpha subunit of the GTP-binding protein which stimulates adenylate cyclase activity. CT-like toxins are found in some strains of V. cholerae non-O1 or V. mimicus, but not in V. parahaemolyticus, another major diarrheagenic vibrio species. A thermostable direct hemolysin (TDH) is thought to be the pathogenic factor causing diarrhea in the vibrio. Hemolysin is the most widely distributed toxin in the pathogenic vibrios and plays various roles in the infection process. Protease activity is also common in the vibrios. Many of the proteases produced by the vibrios are a metalloprotease having a zinc atom immunologically cross reactive to each other. The proteases act not only for processing and activation of protein toxins but also direct toxic factors causing edematous or hemorrhagic skin lesions or disturbance of host defense system.

Food poisoning due to ingestion of two fishes, Yongeichthys nebulosus and Sillago japonica, occurred in Kaohsiung, Taiwan, in February 1997. Two male persons (48 and 58 years old) were poisoned, with symptoms featured by dizziness, nausea, vomiting, numbness, and difficulty in respiration. All of the specimens of fish retained by the victims were combined and consisted of Yongeichthys nebulosus and Sillago japonica. These retained specimens were assayed for anatomical distribution of toxicity (as tetrodotoxin) and all specimens were found to be toxic. The highest toxicity of specimen was 7,650 mouse units (MU) in Y. nebulosus and 1,460 MU in S. japonica. However, the other specimens re-collected from that fish pier were also found to be highly toxic in Y. nebulosus, but nontoxic in S. japonica. Hence, Y. nebulosus was judged as the real causative fish in this food poisoning. The toxins were partially purified from the methanolic extracts of toxic fishes by ultrafiltration and Bio-Gel P-2 column chromatography. Cellulose acetate membrane electrophoresis and high performance liquid chromatography analyses demonstrated that tetrodotoxin was the causative agent of this food poisoning.

Research on poisonous plants was instituted by the United States Department of Agriculture (USDA) as a result of serious livestock poisoning by plants as the pioneers moved west in the mid-to-late 1800s and early 1900s. Historical records indicate the USDA began poisonous plant research in 1894 under the direction of Mr. V. K. Chestnut, a botanist (Table 1 briefly summarizes those who have directed poisonous plant research from the inception to the present). Mr. Chestnut's responsibility (1894-1904) was primarily administrative, although he did extensive field work in Washington and Montana. Temporary field stations were set up to study specific poisonous plant problems. These included field stations at Hugo and Woodland Park, Colorado, and Imperial, Nebraska (1905-1909), to study locoweed; Gunnison, Colorado (1910-1912), to primarily study larkspur; and Greycliff, Montana (1912-1915), to study the poisonous plants of the Yellowstone Valley. Dr. Rodney True replaced Mr. Chestnut in 1904 and in 1905 hired Dr. C. D. Marsh (1905-1930) to establish the temporary field stations listed above. In 1915 a permanent facility was established at Salina, Utah, under the direction of C. D. Marsh who remained in charge until 1930 when he retired; he was followed by A. B. Clawson until 1937 when Dr. Ward Huffman was placed in charge. Research on poisonous plants was located at the Salina Experiment Station until 1955 when the station was closed and the laboratory moved to the campus of Utah State Agricultural College at Logan, Utah, where it is currently located. Dr. Wayne Binns was hired as the director of the laboratory in 1954 and retired in 1972. In 1972 Dr. Lynn F. James, who joined the PRPL staff in July 1957, was appointed as Research Leader and presently directs the research at the Poisonous Plant Research Laboratory.

Many species of lupines contain quinolizidine or piperidine alkaloids known to be toxic or teratogenic to livestock. Poison-hemlock (Conium maculatum) and Nicotiana spp. including N. tabacum and N. glauca contain toxic and teratogenic piperidine alkaloids. The toxic and teratogenic effects from these plant species have distinct similarities including maternal muscular weakness and ataxia and fetal contracture-type skeletal defects and cleft palate. It is believed that the mechanism of action of the piperidine and quinolizidine alkaloid-induced teratogenesis is the same; however, there are some differences in incidence, susceptible gestational periods, and severity between livestock species. Wildlife species have also been poisoned after eating poison-hemlock but no terata have been reported. The most widespread problem for livestock producers in recent times has been lupine-induced "crooked calf disease." Crooked calf disease is characterized as skeletal contracture-type malformations and occasional cleft palate in calves after maternal ingestion of lupines containing the quinolizidine alkaloid anagyrine during gestation days 40-100. Similar malformations have been induced in cattle and goats with lupines containing the piperidine alkaloids ammodendrine, N-methyl ammodendrine, and N-acetyl hystrine and in cattle, sheep, goats, and pigs with poison-hemlock containing predominantly coniine or gamma-coniceine and N. glauca containing anabasine. Toxic and teratogenic effects have been linked to structural aspects of these alkaloids, and the mechanism of action is believed to be associated with an alkaloid-induced inhibition of fetal movement during specific gestational periods. This review presents a historical perspective, description and distribution of lupines, poison-hemlock and Nicotiana spp., toxic and teratogenic effects and management information to reduce losses.

Ponderosa pine (Pinus ponderosa) and the snakeweeds (Gutierrezia sarothrae and G. microcephala) are two groups of range plants that are poisonous to livestock. Ponderosa pine causes late-term abortions in cattle, and the snakeweeds are toxic and also cause abortions in cattle, sheep, and goats. Research is underway at the USDA-ARS-Poisonous Plants Research Laboratory to better understand livestock poisonings caused by grazing ponderosa pine needles and the snakeweeds and to provide methods of reducing losses to the livestock and supporting industries. This review includes the history of the problem, a brief description of the signs of poisoning, the research, to identify the chemical toxins, and current management practices on prevention of poisonings.

Locoweed is the most widespread poisonous plant problem in the western U. S. Eleven species of Astragalus and Oxytropis (and many varieties within these species) cause locoism. Many locoweed species are endemic and are restricted to a narrow niche or habitat. Other locoweed species experience extreme population cycles; the population explodes in wet years and dies off in drought. A few species, such as O. sericea, are relatively stable and cause persistent poisoning problems. Knowledge of where locoweeds grow and the environmental conditions when they become a threat is important to manage livestock and avoid poisoning. Locoweeds are relatively palatable. Many locoweeds are the first plants to begin growth in the spring and regrow in the fall. Livestock generally prefer the green-growing locoweeds to other forage that is dormant in the late fall, winter, and spring. The most effective management strategy is to deny livestock access to locoweeds during critical periods when they are more palatable than the associated forage. Herbicides can control existing locoweed populations and provide "safe" pastures for critical periods. However, locoweed seed in soil will germinate and re-establish when environmental condition are favorable. Good range management and wise grazing strategies can provide adequate forage for livestock and prevent them from grazing locoweed during non-critical periods of the year when it is relatively less palatable than associated forages.

Locoweed poisoning is a chronic disease that develops in livestock grazing for several weeks on certain Astragalus and Oxytropis spp. that contain the locoweed toxin, swainsonine. The purpose of this review is to present recent research on swainsonine toxicokinetics and locoweed-induced clinical and histologic lesions. Swainsonine inhibits cellular mannosidases resulting in lysosomal storage disease similar to genetic mannosidosis. Diagnosis of clinical poisoning is generally made by documenting exposure, identifying the neurologic signs, and analyzing serum for alpha-mannosidase activity and swainsonine. All tissues of poisoned animals contained swainsonine, and the clearance rates from most tissues was about 20 hours (T1/2 half life). The liver and kidney had longer rate of about 60 hours (T1/2). This suggests that poisoned animals should be allowed a 28-day withdrawal to insure complete swainsonine clearance. Poisoning results in vacuolation of most tissues that is most obvious in neurons and epithelial cells. Most of these histologic lesions resolved shortly after poisoning is discontinued; however, some neurologic changes are irreversible and permanent.

Larkspurs (Delphinium spp.) are toxic plants that contain numerous diterpenoid alkaloids which occur as one of two structural types: (1) lycotonine, and (2) 7,8-methylenedioxylycoctonine (MDL-type). Among the lycoctonine type alkaloids are three N-(methylsuccinimido) anthranoyllycoctonine (MSAL-type) alkaloids which appear to be most toxic: methyllycaconitine (MLA), 14-deacetylnudicauline (DAN), and nudicauline. An ester function at C-18 is an important structural requirement for toxicity. Intoxication results from neuromuscular paralysis, as nicotinic acetylcholine receptors in the muscle and brain are blocked by toxic alkaloids. Clinical signs include labored breathing, rapid and irregular heartbeat, muscular weakness, and collapse. Toxic alkaloid concentration generally declines in tall larkspurs with maturation, but alkaloid concentration varies over years and from plant to plant, and is of little use for predicting consumption by cattle. Knowledge of toxic alkaloid concentration is valuable for management purposes when cattle begin to eat larkspur. Cattle generally begin consuming tall larkspur after flowering racemes are elongated, and consumption increases as larkspur matures. Weather is also a major factor in cattle consumption, as cattle tend to eat more larkspur during or just after summer storms. Management options that may be useful for livestock producers include conditioning cattle to avoid larkspur (food aversion learning), grazing tall larkspur ranges before flowering (early grazing) and after seed shatter (late grazing), grazing sheep before cattle, herbicidal control of larkspur plants, and drug therapy for intoxicated animals. Some potentially fruitful research avenues include examining alkaloid chemistry in low and plains larkspurs, developing immunologic methods for analyzing larkspur alkaloids, developing drug therapy, and devising grazing regimes specifically for low and plains larkspur.

Locoweeds (species of Oxytropis and Astragalus containing the toxin swainsonine) cause severe adverse effects on reproductive function in livestock. All aspects of reproduction can be affected: mating behavior and libido in males; estrus in females; abortion/embryonic loss of the fetus; and behavioral retardation of offspring. While much research has been done to describe and histologically characterize these effects, we have only begun to understand the magnitude of the problem, to define the mechanisms involved, or to develop strategies to prevent losses. Recent research has described the effects of locoweed ingestion in cycling cows and ewes. Briefly, feeding trials with locoweeds in cycling and pregnant cows have demonstrated ovarian dysfunction in a dose-dependent pattern, delayed estrus, extended estrous cycle length during the follicular and luteal phases, delayed conception (repeat breeders), and hydrops and abortion. Similar effects were observed in sheep. In rams, locoweed consumption altered breeding behavior, changed libido, and inhibited normal spermatogenesis. Neurological dysfunction also inhibited normal reproductive behavior, and some of these effects were permanent and progressive. In this article we briefly review the pathophysiological effects of locoweeds on reproduction.