Journal of natural toxins最新文献

Experimental PSP contamination of adult Pacific oysters (Crassostrea gigas) by the toxic dinoflagellate Alexandrium minutum Halim (120 cells.mL-1 continuously maintained in each flume) was carried out in a recirculated seawater system to obtain toxin levels above the safety threshold. In these conditions, 150 to 300 micrograms STX.eq.100 g-1 of shellfish tissues were produced at 16 degrees C within 8 to 15 days, corresponding to field values observed along French coasts. Diets based on non-toxic flagellates or diatoms were then used to detoxify the contaminated oysters. Despite large individual variations in toxin levels at the end of the contamination period, detoxification times were of the same order of magnitude (3 to 4 days), reaching a toxin level equal to or less than the safety threshold. These variations were most likely related to marked individual variability in valve and/or clearance activities. No significant differences in detoxification rates were found when oysters were fed Isochrysis galbana, Tetraselmis suecica, Thalassiosira weissflogii, or Skeletonema costatum. The different biochemical compositions of each algal species appeared to have no significant effect on detoxification rates. GTX2/GTX3 were the dominant compounds found in shellfish tissues during depuration, whereas C toxins were quite low (< 2 micrograms STX.eq.100 g-1) and STX or NeoSTX undetectable. These results do not suggest any bioconversion of paralytic toxins but indicate good correlation between the toxin composition of Alexandrium and oyster tissues.

Successive extraction of Thyme plant, Thymus capitatus (L.) Hoffm. and Link (Lamiaceae), by different solvents of increasing polarity, showed that potency was highly attributed to the non-polar fraction (e.g., petroleum ether) when tests were carried out against the larvae and adults of Culex pipiens (L). Of special concern to the mosquitocidal activity, the following fractions and isolates were recognized: the volatile oil, unsaponifiable portion, and certain compounds isolated from the unsaponifiable portion (e.g., Thymol, alpha-Amyrin, Carvacrol + beta-Caryophyllene). The volatile oil, Thymol, and the unsaponifiable portion proved high larvicidal potency against the tested insect (LC50 = 49.0, 58.0, and 100.0 ppm, respectively). Non-lethal concentrations of these substances synergized the toxicity of Malathion, while induced additive or antagonistic effects when mixed with Permethrin or Pirimiphos-methyl. The unsaponifiable portion and volatile oil showed the highest adulticidal potency (LC50 = 0.0070 and 0.0076 mg/cm2, respectively). The efficacy of the tested candidates as repellent agents was found in the following order: unsaponifiable portion > alpha-Amyrin > Thymol > volatile oil > Carvacrol + beta-Caryophyllene. Thymol as well as volatile oil affected egg hatchability, causing Sterility Indices accounting for 0.70 and 0.74, respectively, while the unsaponifiable portion showed lower degree of sterility (0.81). The results obtained in this study may shed light on the importance of T. capitatus as a probable source of some biologically active agents for mosquito control in the future.

To establish the safety data of shellfish in southern Taiwan, a total of 3,074 specimens of 30 shellfish species were seasonally collected from August 1995 to March 1997. These samples were assayed for the presence of tetrodotoxin (TTX) and paralytic shellfish poisons (PSP) by the bioassay methods. It was found that some major shellfish including oyster, clam, ear shell, and purple clam were nontoxic, but four species, Babylonia formosae, Niotha clathrata, Natica lineata, and Natica vitellus, were toxic. The toxic percentages of these four species was 1% in B. formosae, 56% in N. clathrata, 37% in N. lineata, and 23% in N. vitellus. The toxic composition was TTX in B. formosae. In the other three shellfish types the toxic composition was TTX and PSP.

Recent study showed that transferrin receptors were concentrated on the plasma membrane of brain endothelia cells and mediated transcytosis of transferrin (Tf) through the blood-brain barrier (BBB). This property allows the transferrin to act as the brain drug transporter vector. The present investigation examined the pharmacokinetic behavior of nerve growth factor (NGF), which was conjugated to transferrin by the avidin/biotin technology, especially its brain-uptake efficiency. The area under the plasma concentration curve and the mean residence time were not significantly different for either bio-NGF or bio-NGF/AV-Tf. At the first hour after single intravenous injection, the BBB permeability surface area product of bio-NGF/AV-Tf was 0.77 microliter/min/g; it was about 8-fold higher than that of bio-NGF, and equal to that of AV-OX26. The delivery of bio-NGF/AV-Tf to brain was 0.075% of injected dose per gram brain, and it was 5-fold higher than that of bio-NGF, and 2-fold higher than that of AV-OX26. In summary, these studies demonstrated that the use of Tf as brain drug delivery vector was as effective in transporting biotinylated therapeutics as OX26, and avoided the disadvantages of its antigenicity.

Crotoxin is known to desensitize the nicotinic receptor of Torpedo marmorata and Electrophorus electricus electroplaques. The aim of the present study was to elucidate whether the postsynaptic effect of crotoxin at a mammalian muscle end-plate is also caused by receptor desensitization or results from a curaremimetic action. For this purpose, we investigated the action of 4-aminopyridine (4-AP) on crotoxin-induced blockade of miniature end-plate potentials (m.e.p.p.s) and of the depolarization of end-plates produced by carbachol. The experiments were carried out in guinea-pig diaphragms bathed in Tyrode solution at 37 degrees C and gassed with 95% O2, 5% CO2. The potentials were measured with conventional techniques using glass microelectrodes. Even at low concentrations, crotoxin blocked the m.e.p.p.s and this blockade was antagonized by 4-AP. Neostigmine was without effect. 4-AP did not restore the m.e.p.p.s blocked by either d-tubocurarine (dTc) or beta-bungarotoxin (beta-BTX). 4-AP also antagonized the crotoxin-induced blockade of the end-plate depolarization produced by carbachol. These results show that the postsynaptic effect of crotoxin at the guinea-pig muscle end-plate also results from nicotinic receptor desensitization.

In the present study, the effects of intramuscular (i.m.) injection of a sublethal dose (0.015 microgram/gm b.wt.) of Naja haje venom were histologically and histochemically examined in the hepatic tissues of rabbits after 3, 6, and 12 hr. of envenomation. Three hours after venom injection, the hepatic cells showed a generalized cytoplasmic granulation and cellular swelling accompanied with narrowing of the sinusoidal spaces. Occurrence of inflammatory cells and hypertrophy of Kupffer cells were also noticed. After 6 hr. of envenomation, the hepatic tissues revealed severe cellular swelling, cytoplasmic deterioration, nuclear pyknosis, and appearance of numerous basophilic granules. The central veins were engorged with hemolyzed blood. Hepatic tissues investigated after 12 hr. of envenomation exhibited highly damaged hepatic cells to the extent that the individual cell cannot be identified and remnants of cell debris were seen intermixed together. Some hepatic cells were intensively swollen and their contents were dissoluted except for a few dusty cytoplasmic granules and pyknotic nuclei. The histochemical observations showed a time dependent depletion in polysaccharide, lipid, and protein contents in the hepatic cells of the envenomed groups. As for the nucleic acids, slight depletion of RNA together with no changes in DNA contents were observed by 3 hr. of envenomation. Nevertheless, severe degrees of RNA depletion and moderate contents of DNA were recorded in 6 hr. envenomed tissues. Highly obvious depletion of RNA and DNA were demonstrated by 12 hr. after venom injection. From the above results, it is obvious that cobra venom induces a hepatotoxic action reflected by alterations in the histological and histochemical patterns of the hepatic tissues. These alterations are initiated at early stages of envenomation and could indicate a disturbance in the functional activities of the liver during envenomation.

Fumonisin B1 (FB1) is the most abundant of a series of sphingosine analog mycotoxins produced by the fungus Fusarium moniliforme, a ubiquitous contaminant of stored corn (maize) worldwide. FB1 exhibits a variety of biological activities including phytotoxicity, which is of particular interest for its potential role as a virulence factor to facilitate invasion of plant tissues by the fungus. Droplets of FB1 solution applied to the leaf surface of jimsonweed, black nightshade, and susceptible tomatoes caused necrosis, growth inhibition, and death. With Arabidopsis thaliana grown on agar plates, an IC50 (concentration causing half maximal phytotoxicity) of less than 1 ppm was observed. [3H]FB1 was prepared by biosynthetic incorporation of commercially-available radiolabeled presumptive precursors into the toxin in rice medium solid cultures of F. moniliforme JW#1. The labeled toxin produced by incorporation of [9,10(-3)H]palmitate induced phytotoxic symptoms identical to unlabeled material, indicating it had full biological activity. The area of necrosis on treated leaves was similar in light and dark treated plants. Using liquid scintillation counting to quantify radioactivity in excised plant parts, over 95% of the [3H]FB1 radioactivity applied to leaves of light or dark-treated plants was recovered from the treated leaf. When [3H]FB1 was applied to a wound site on target plants, severe damage occurred at the site of FB1 application and in tissue above the site. These results indicate that FB1 applied to intact surfaces of target plants exhibits primarily contact activity. Translocation of FB1 is limited, occurring only when FB1 is applied to a wound site, and it results in damage to tissue above the point of application, indicating that FB1 is xylem mobile.

The effects of Russell's viper venom on vasoactive mediators and renal hemodynamics were studied in five mongrel dogs. Intravenous administration of Russell's viper venom to the dogs caused a reduction of mean arterial pressure, renal blood flow, and glomerular filtration rate. The filtration fraction was decreased. This was accompanied by a rise in plasma norepinephrine, endothelin, 6-keto-PGF1 alpha, a stable metabolite of PGI2, and TXB2, a metabolite of TXA2. Plasma levels of epinephrine and dopamine showed no significant changes. The increase of plasma levels of both vasodilatator and vasoconstrictor were critical to systemic and renal hemodynamics. While vasodilatation predominated in the systemic circulation and resulted in hypotension, vasoconstriction played a major role in decreasing renal hemodynamics. Decreased renal blood flow and decreased glomerular filtration rate were the result of renal vasoconstriction and hypotension.

Pathophysiological effects of Russell's viper venom (RVV) on renal function are reviewed. The evidence in experimental animals on the mechanisms of venom action in relation to changes in either extrarenal or intrarenal factors is considered. The cardiovascular system and renal hemodynamics are affected by the venom. Mean arterial blood pressure, heart rate, cardiac output, and renal hemodynamics decrease, while total peripheral vascular resistance and renal vascular resistance increase in the initial post-injection period of envenoming. After the transitory decrease, all parameters for general circulation gradually increase, returning to near normal level within 30 min, while an increase in renal vascular resistance and decreases in renal blood flow and glomerular filtration rate are still apparent 48 h after envenomation. The effects of venom on renal vasoconstriction are discussed. Possible factors, especially humoral factors, inducing these changes are considered. Russell's viper venom is also able to affect renal tubular cells directly. This can be explained based on available data from in vitro studies. Different studies have been performed to investigate venom action in the isolated perfused kidney, changes in the characteristic polarization of the cell membrane, changes in mitochondria activity and changes in Na, K-ATPase activity of the tissue of both the renal cortex and medulla during envenomation.

Fumonisin B1 (FB1) is the most abundant of a series of sphingosine analog mycotoxins produced by the fungus Fusarium moniliforme, a ubiquitous contaminant of stored corn (maize) worldwide. FB1 exhibits a variety of biological activities including phytotoxicity, which is of particular interest for its potential role as a virulence factor to facilitate invasion of plant tissues by the fungus. Droplets of FB1 solution applied to the leaf surface of jimsonweed, black nightshade, and susceptible tomatoes caused necrosis, growth inhibition, and death. With Arabidopsis thaliana grown on agar plates, an IC50 (concentration causing half maximal phytotoxicity) of less than 1 ppm was observed. [3H]FB1 was prepared by biosynthetic incorporation of commercially-available radiolabeled presumptive precursors into the toxin in rice medium solid cultures of F. moniliforme JW#1. The labeled toxin produced by incorporation of [9,10-3H]palmitate induced phytotoxic symptoms identical to unlabeled material, indicating it had full biological activity. The area of necrosis on treated leaves was similar in light and dark treated plants. Using liquid scintillation counting to quantify radioactivity in excised plant parts, over 95% of the [3H]FB1 radioactivity applied to leaves of light or dark-treated plants was recovered from the treated leaf. When [3H]FB1 was applied to a wound site on target plants, severe damage occurred at the site of FB1 application and in tissue above the site. These results indicate that FB1 applied to intact surfaces of target plants exhibits primarily contact activity. Translocation of FB1 is limited, occurring only when FB1 is applied to a wound site, and it results in damage to tissue above the point of application, indicating that FB1 is xylem mobile.