Journal of Toxicology-toxin Reviews最新文献

{"title":"MODIFICATION OF BIOLOGICAL PROPERTIES OF PROTEIN TOXINS BY STEPWISE IODINATION","authors":"L. Heneine, I. F. Heneine","doi":"10.1081/TXR-100108557","DOIUrl":"https://doi.org/10.1081/TXR-100108557","url":null,"abstract":"By gradual incorporation of stable iodine into toxins and whole venoms it is possible to abolish completely the physiological, lesion and lethal properties of the native components. The properties of iodinated antigens and from antibodies generated by these detoxified derivatives, are presented. The hapten is incorporated into tyrosyl and histidyl residues. The derivatives can be obtained in less than one hour. Within the same batch of protein, there is a determinable stoichiometric ratio hapten/protein to achieve the desired modified properties of the derivative. The iodinating solutions are easy to prepare, can be accurately standardized and have unlimited shelf lives. The cost of the whole procedure is very low. No side-effects, local or systemic were observed, even with prolonged use of the derivatives. The method was applied to toxic components and whole venom of the scorpion Tityus serrulatus, and the hypertensive, bradipneic, oliguric, lesional, lethal and cytotoxic effects were completely abolished. Polyclonal antibodies generated by these iodinated antigens neutralized the virulent effects of native components and reversed the α effects of the whole venom in frog sciatic nerves. They conferred active immunization in mice, rats, guinea pigs, goats, horses and pigeons. Crotoxin and whole venom of Crotalus durrissus terrificus lost the lesional and lethal activity, but conserving the immunogenic capacity. They produced antibodies against the native components, giving also vaccinal protection. While the virulent crotalic antigens had a cytotoxic activity, the iodinated antigens were highly mitogenic with human white cells. Five bothropic venoms were neutralized in the hemorrhagic, tissue lesion and lethal capacity, the derivatives were immunogenic. Repetitive sublethal doses of scorpionic, crotalic and bothropic venoms lead invariably to an amyloid-like deposit in tissues, whereas the iodinated samples were ineffective. Allergenic extracts of Schistosoma mansoni can be transformed into anallergic derivatives that retains antigenic properties. Violently allergenic extracts of Ascaris lumbricoides suum can be completely deactivated with iodination, but conserved immunological competence. Cholera, tetanus and botulinum toxins, as iodinated toxoids, had its lesional and lethal capacity completely avoided. Physiological proteins with strong biological activity can also be rendered innocuous. Iodinated insulin lost its capacity to lower blood glucose levels, but induced high avidity antibodies in guinea-pigs and rabbits. By iodination, kallikrein can be turned unable to contract rat uterus, and to liberate kinins from kinninogen. Modified tonin do not increase the blood pressure in rats. Aqueous extracts of Leptospira canis and L. icterohaemorrhagiae after iodination, were innocuous to hatched eggs, and immunogenic in mice and rabbits. A lectin from Macrotylema axillare, lost the hemaglutination capacity with only 75% of iodine saturation. The der","PeriodicalId":17561,"journal":{"name":"Journal of Toxicology-toxin Reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84583579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"THE CHARACTERIZATION OF CONOTOXINS§","authors":"A. Craig","doi":"10.1081/TXR-100100315","DOIUrl":"https://doi.org/10.1081/TXR-100100315","url":null,"abstract":"Conotoxins are peptide toxins synthesized by marine cone snails for both prey entrapment and defense. The peptides, when injected into the prey, cause immobilization and death. Cone snails are widely distributed in tropical waters, their prey includes fish, worms and other marine snails. The peptide toxins have very high specificity and selectivity for a variety of neuro receptors and ion channels. This makes the toxins very useful in studies aimed at identifying receptors and their ligands, as well as in drug development studies. Conotoxins are notable at the level of primary amino acid sequence for their high percentage of cysteine residues and other post-translational modifications including hydroxylation of proline, γ-carboxylation of glutamate, pyroglutamic acid formation, bromination of tryptophan and C-terminal amidation. This review describes traditional and more novel techniques for the characterization of conotoxins. In particular, the identification of the nature and the site of post-translational modifications is emphasized. Among the different techniques used to characterize the conotoxins, the important role played by mass spectrometry is emphasized.","PeriodicalId":17561,"journal":{"name":"Journal of Toxicology-toxin Reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77647937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ACTION OF VITAMIN C AGAINST ACETAMINOPHEN-INDUCED HEPATORENAL TOXICITY IN RATS","authors":"M. El-Ridi, T. Rahmy","doi":"10.1081/TXR-100102324","DOIUrl":"https://doi.org/10.1081/TXR-100102324","url":null,"abstract":"Effects of different doses of vitamin C against acetaminophen (APAP)-induced hepatorenal toxicity was investigated in male rats. The experimental groups included, a control group which received vehicle, a group intraperitoneally injected with a single dose of vitamin C (320 mg/kg body weight (b.wt.)), a group which received an oral overdose of APAP (1 g / kg b.wt.), as well as three groups administered the APAP overdose followed by a single dose of vitamin C (80, 160 or 320 mg/kg b.wt). All animals were watched for 24 hours, after which the mortality rate and serum levels of the hepatorenal indices were measured. Liver glutathione level and the ultrastructure of hepatic and renal tissues were also studied. Administration of APAP overdose induced a high mortality rate and hepatorenal toxicity as indicated by significantly higher levels of hepatorenal indices and decreased liver glutathione. It also caused cellular alterations and necrosis of hepatocytes and some renal cortical cells. However, injection of vitamin C alone caused no abnormalities. The injection of vitamin C after APAP administration decreased the hepatorenal toxicity in a dose-dependent manner. The highest dose of vitamin C normalized the levels of liver glutathione and serum hepatorenal indices except for bilirubin. It also protected hepatic and renal cells except for slight dilatation of rough endoplasmic reticulum and glycogen depletion in some hepatocytes, as well as the presence of lysosomal structures in cortical tubular epithelia. No fatalities were seen in rats treated with the highest two doses of vitamin C. It could be concluded that the highest dose of vitamin C prevented against the lethal effect of APAP overdose, although it incompletely protected against hepatorenal toxicity.","PeriodicalId":17561,"journal":{"name":"Journal of Toxicology-toxin Reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87667754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BIOCHEMICAL STUDIES OF VERRUCARIN J IN MALE MICE LIVER","authors":"N. El-Sawi, M. El-wassimy, Osama A. Youssef","doi":"10.1081/TXR-100102323","DOIUrl":"https://doi.org/10.1081/TXR-100102323","url":null,"abstract":"Eight treated groups of 10 male mice that were injected with two sublethal doses of verrucarin J (0.9 and 0.5 mg/kg body weight) for two, four, six and eight weeks (for each dose) were compared with eight groups of control mice. Serum total protein and albumin were decreased in treated groups. Globulins, total lipids, total bilirubin, conjugated bilirubin and unconjugated bilirubin were increased compared with the control groups. Liver disease is often clinically assessed using serum enzyme activities such as glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, γ-glutamyl transferase, alkaline phosphatase, and 5′-nucleotidase. The levels of these enzymes were increased in serum of treated groups compared with the control groups. The results indicate that the second dose produced less dramatic biochemical changes than the first dose in the above-mentioned parameters.","PeriodicalId":17561,"journal":{"name":"Journal of Toxicology-toxin Reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80239193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"INTRASPECIFIC VARIATION IN SCORPION LEIURUS QUINQUESTRIATUS VENOM COLLECTED FROM EGYPT (SINAI AND ASWAN DESERTS)","authors":"M. Omran, A. Mcvean","doi":"10.1081/TXR-100102322","DOIUrl":"https://doi.org/10.1081/TXR-100102322","url":null,"abstract":"Leiurus quinquestriatus is a single species genus scorpion of Saharan origin, which has penetrated the Mediterranean region. The Sinai Isthmus is believed to be the region in which the subspecies L.q. quinquestriatus gives way to L.q. hebraeus. To test whether there are qualitative differences in the venom from Leiurus quinquestriatus inhabiting two different geographic regions, venom was obtained from scorpions collected from Aswan in Southern Egypt and from the Southern region of Sinai Peninsula, Egypt. Electrophoresis and a densitometric gel scan showed that in the molecular weight range above that known to include toxins, venom of Aswan origin contained several protein bands that were absent from Sinai-sourced venom. In contrast Sinai venom appeared to have a larger proportion of protein in the molecular weight range known to include toxins. Such differences may reflect a response to local ecological conditions. Application of equal concentrations by weight of the two venoms to rat ileum showed no difference in the contraction produced by the lowest effective dose (0.2 μg ml-1) but at higher doses (0.5, 1.0 & 2.0 μg ml-1) venom from Aswan induced stronger and more sustained contractions with a different time course than did Sinai scorpion venom. Geographically related intra-specific variation in venom composition might be important in treating the pathophysiological effects of scorpion venom. This is the first time that differences in the venom components and their physiological effectiveness has been demonstrated for the scorpion L. quinquestriatus venom collected from two distinct areas in Egypt.","PeriodicalId":17561,"journal":{"name":"Journal of Toxicology-toxin Reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77638576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SPHINGOSINE- AND CERAMIDE-ANALOG TOXINS—AN UPDATE","authors":"W. Shier, A. Shier","doi":"10.1081/TXR-100102321","DOIUrl":"https://doi.org/10.1081/TXR-100102321","url":null,"abstract":"The first sphingosine-analog toxin was isolated in 1978 by Carter and Rinehart, who recognized both the analogy to sphingosine and its potential as a mechanism of action. However, interest in the field has expanded greatly since the recognition by Riley and associates that fumonisins, putative environmental tumor promoters that contaminate the food supply of hundreds of millions of people worldwide, are also sphingosine analogs. Sphingosine is a component of sphingolipids, some of which play structural roles (e.g., sphingomyelin), while others (sphingosine, ceramide and glycosphingolipids) appear to play important roles in cellular regulation. Sphingolipid analogs may act by altering normal sphingolipid metabolism, or by interacting as agonists or antagonists with sphingolipid-binding sites in regulatory processes. In the discussion that follows sphingosine analogs are classified as (i) simple sphingosine analogs isolated primarily from marine lower animals and characterized by either primary amines on linear chains or heterocyclic rings; (ii) myriocin-type analogs characterized by a 1-carboxylic acid moiety, which are antifungal agents produced by other fungi; (iii) fumonisins and AAL-toxins, a large but narrowly-defined structural class produced by phytopathogenic fungi; and (iv) vis-1-deoxysphingosines, which a tail-to-tail dimers obtained from marine lower animals. Ceramide analogs are classified as either simple ceramides or glycosphingolipids. These sphingosine and ceramide analogs exhibit a wide range of biological activities.","PeriodicalId":17561,"journal":{"name":"Journal of Toxicology-toxin Reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90258572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ACYLPOLYAMINES: MASS SPECTROMETRIC ANALYTICAL METHODS FOR Araneidae SPIDER ACYLPOLYAMINES","authors":"Y. Itagaki, T. Nakajima","doi":"10.1081/TXR-100100314","DOIUrl":"https://doi.org/10.1081/TXR-100100314","url":null,"abstract":"A new class of compounds, acylpolyamine has been isolated from spider venom constituents. Recent advances in highly sensitive mass spectrometric techniques have been applied successfully to characterize these acylpolyamines even with the use of a single venom gland. This has been achieved, in part, by improvements in fast atom bombardment mass spectrometry (FAB), continuous flow (FRIT) FAB-MS combined with reversed-phase high performance liquid chromatography (HPLC), matrix assisted laser desorption/ionization (MALDI) and high energy collision induced dissociation (CID) tandem MS/MS. Crude venom analysis without chromatographic separation can be realized directly by MALDI-MS. A charge-remote fragmentation method has provided abundant structure-related product ions and have reduced the quantity of required venom for the structure analysis of acylpolyamines. These mass spectrometric methods were proved to be useful for the analysis of complex constituents of spiders and other arthropod venom glands.","PeriodicalId":17561,"journal":{"name":"Journal of Toxicology-toxin Reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77398260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"THE FUMONISIN PARADOX: A REVIEW OF RESEARCH ON ORAL BIOAVAILABILITY OF FUMONISIN B1, A MYCOTOXIN PRODUCED BY FUSARIUM MONILIFORME","authors":"W. Shier","doi":"10.1081/TXR-100100319","DOIUrl":"https://doi.org/10.1081/TXR-100100319","url":null,"abstract":"The fumonisins are a series of mycotoxins produced by Fusarium moniliforme, a ubiquitous contaminant of stored corn (maize) worldwide. Consumption of food products contaminated with F. moniliforme hasbeen correlated with increased risk of human esophageal cancer in epidemiological studies in southern Africa and China. The most abundant component, fumonisin B1 (FB1), was isolated from F. moniliforme culture extracts using a short-term tumor promoter bioassay to guide the fractionation. Purified FB1 has been confirmed to act as a tumor promoter in animal model systems; to cause hepatocellular carcinoma, cirrhosis and proximal tubule nephrosis in rats; and to mediate agriculturally significant diseases associated withconsumption of F. moniliforme-contaminated feeds, including equine leukoencephalomalacia and porcine pulmonary edema. However, studies on the toxicokinetics of radiolabeled and unlabeled FB1 carried out by three research groups in five animal species all indicate that it is absorbed very poorly if at all when administered orally. There is no evidence for functionally significant metabolism of FB1 in vivo. These observations result in what might be called the “fumonisin paradox”—how can the toxin cause agriculturally significant diseases and possibly human cancer if it is not effectively adsorbed after oral administration? There are several plausible explanations including (i) an unknown, readily bioavailable contaminating toxin is responsible; (ii) higher FB1 bioavailability at lower dose; (iii) greater conversion to active metabolites at lower dose; (iv) bioaccumulation and (v) effective uptake of FB1 derivatives that are readily converted back to FB1 or active metabolites in the body. The full extent of the threat to food safety posed by the fumonisins will not be known until the factors affecting oral bioavailability are understood.","PeriodicalId":17561,"journal":{"name":"Journal of Toxicology-toxin Reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87684582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MASS SPECTRAL STUDIES OF SNAKE VENOMS AND SOME OF THEIR TOXINS","authors":"K. Tubbs, R. Nelson, J. R. Krone, A. Bieber","doi":"10.1081/TXR-100100313","DOIUrl":"https://doi.org/10.1081/TXR-100100313","url":null,"abstract":"The profound effect of Biological Mass Spectrometry (MS) on protein analysis has been amplified by recent developments in analytically based matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS). This review provides a brief synapses of snake toxin based research allocating mass spectrometric immunoassay (MSIA) and bioreactive probe tips technologies. Contingent upon advances in Biological MS has been the movement of mass spectrometric applications into array based technology. Biomolecular interaction analysis interfaced with mass spectrometry (BIA/MS) exemplifies the diverse potential of chip based techniques, combining the powerful front-end analysis of biological interaction events with the dynamic precision of MALDI-MS mass specific assignment, to demonstrate “lab on a chip” technology. Analysis of other snake venoms and related toxins by electrospray ionization and tandem mass spectrometry as well as capillary electrophoresis combined with MALDI-MS are included. The development of new and powerful mass spectral methods for the study of biopolymers have increased substantially in recent years. Matrix-assisted laser desorption ionization (MALDI) , secondary ion , electrospray , and tandem mass spectrometry are among the mass spectral techniques that have been used to study biopolymers . Mass spectrometry, when combined with the mass spectrometric immunoassay, enzymatically active probe elements and biomolecular interaction analysis, has given rise to a number powerful bio-analytical methods for protein studies. Fig. explores some of the ways in which these approaches are being applied in protein analysis. The methods, which are rapid, sensitive and accurate, can be used to study pure proteins, complex mixtures of proteins and selected proteins in a complex mixture. The study of toxins and proteins from snake venoms by mass spectrometric techniques has been rather limited, even though the new techniques appear ideally suited for examining complex mixtures of proteins commonly found in snake venoms. This review of the current literature will summarize work in which mass spectrometric techniques have been successfully applied to the study of venoms and proteins obtained from them. The review will not be totally inclusive, but will illustrate some of the ways that mass spectrometric techniques have been used in researching venoms and proteins. The focus of the review will be on studies of myotoxins and neurotoxins acquired from rattlesnake venoms, thus illustrating the systematic use of several mass spectrometry based techniques for analyzing intrinsic venom proteins. Figure 1. Overview of biological mass spectrometry applied to the study of snake toxin proteins.","PeriodicalId":17561,"journal":{"name":"Journal of Toxicology-toxin Reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81342816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MASS SPECTRAL INVESTIGATIONS ON MICROORGANISMS","authors":"T. Krishnamurthy, U. Rajamani, P. Ross, R. Jabbour, H. Nair, J. Eng, J. Yates, Mike T. Davis, D. C. Stahl, Terry D. Lee","doi":"10.1081/TXR-100100316","DOIUrl":"https://doi.org/10.1081/TXR-100100316","url":null,"abstract":"Bacterial cells undergo lysis readily, when suspended in mild aqueous acids, and release the cellular proteins along with other biomolecules. Molecular masses of the protein biomarkers released in-situ from individual intact bacterial cells could be directly measured by mass spectrometry. Limited sample clean up may be required at times, prior to mass spectral analysis, to remove any ionizable impurities such as salts, buffers and deergents. The marker proteins specific for individual genus, species and strains were determined by the comparison of the biomarkers measured for several closely related organisms. Even though there is a probability of over 4000 cellular proteins expressed in any single bacterial cell, only a small fraction of the projected marker proteins are identified consistently during the process. This could be due to the variation in the ionization properties of the proteins and the limited energy available to prompt their ionization. Variation in the sample processing and culture conditions had little effect in the marker proteins observed during the process. This experimental procedure enables the distinction of gram positive as well as gram negative cellular pathogens and their corresponding non-pathogenic counterparts. The identity of few bacterial cells present in unknown samples can be easily, rapidly and accurately established by adopting a procedure involving simple sample processing followed by direct mass spectral analysis and data processing. Thus, an uncomplicated approach has been developed to resolve a complex problem involving cellular pathogens. This method has enormous application potential in the rapid identification and subsequent prevention of any potential health hazard caused by the pathogenic bacteria, either under natural or induced conditions. There is a great potential for the total automation of the entire process in the future for simpler but more effective unattended operations in the laboratory as well as in the field.","PeriodicalId":17561,"journal":{"name":"Journal of Toxicology-toxin Reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83558254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}