Cysteine toxicity

Schnellman, R.G., Lock, E.A. and Mandel, L.J. (1987). A mechanism of 5-(l,2,3,4,4-Pentachloro-l,3-butadienyl)-L-cysteine toxicity to rabbit proximal tubules. Toxicol. Appl. Pharmacol. 90 513-521. 

S-(1,2,3,4,4-pentachloro-1,3-butadienyl)-L-cysteine toxicity to rabbit renal proximal tubules. Toxicol AppI Pharmacol 90 513-521. 

Although molybdenum is an essential element, excess levels can have deleterious effects. The LD q and TLV values of the most common Mo compounds are Hsted in Table 3 (63,64). In general the toxicity of Mo compounds is considered to be low. For example, M0S2 has been found to be virtually nontoxic even at high levels. Certain Mo compounds such as MoCl and Mo(CO), have higher toxicity because of the chemical nature and reactivity of these compounds rather than the Mo content. Supplementary dietary Cu ", thiosulfate, methionine, and cysteine have been shown to be effective in alleviating Mo toxicity in animals. 

The ability to identify and quantify cyanobacterial toxins in animal and human clinical material following (suspected) intoxications or illnesses associated with contact with toxic cyanobacteria is an increasing requirement. The recoveries of anatoxin-a from animal stomach material and of microcystins from sheep rumen contents are relatively straightforward. However, the recovery of microcystin from liver and tissue samples cannot be expected to be complete without the application of proteolytic digestion and extraction procedures. This is likely because microcystins bind covalently to a cysteine residue in protein phosphatase. Unless an effective procedure is applied for the extraction of covalently bound microcystins (and nodiilarins), then a negative result in analysis cannot be taken to indicate the absence of toxins in clinical specimens. Furthermore, any positive result may be an underestimate of the true amount of microcystin in the material and would only represent free toxin, not bound to the protein phosphatases. Optimized procedures for the extraction of bound microcystins and nodiilarins from organ and tissue samples are needed. 

Cadmium is extremely toxic and accumulates in humans mainly in the kidneys and liver prolonged intake, even of very small amounts, leads to dysfunction of the kidneys. It acts by binding to the —SH group of cysteine residues in proteins and so inhibits SH enzymes. It can also inhibit the action of zinc enzymes by displacing the zinc. 

GSH (because of the sulfhydryl group of its cysteine, which is the business part of the molecule). A number of potentially toxic electrophilic xenobiotics (such as certain carcinogens) are conjugated to the nucleophilic GSH in reactions that can be represented as follows ... 

Mercuric chloride, other mercury-containing antibacterials and silver will inhibit enzymes in the membrane, and for that matter in the cytoplasm, which contain thiol, -SH, groups. A similar achon is shown by 2-bromo-2-nitropropan-l,3-diol (bronopol) and iso-thiazolones. Under appropriate condihons the toxic action on cell thiol groups may be reversed by addition of an extrinsic thiol compound, for example cysteine or thioglycollic aeid (see also Chapters 12 and 23). 

In a different way, metallic-core nanoparticles [346-349] (prepared cf. Section 3.10) equipped with biocompatible coats such as L-cysteine or dextrane may be exploited for highly efficient and cell-specific cancer cell targeting, i.e., for improving diagnosis and therapy of human cancer. In a recent proof-of-principle experiment an unexpectedly low toxicity of the L-cysteine-covered cobalt nanoparticles was demonstrated [433] For diagnostic purposes, it is expected to use the advantageous magnetic properties of the metallic-core nanoparticles to obtain a contrast medium for MRI with considerably increased sensitivity, capable to detect micro-metastases in the environment of healthy tissues [434 37]. 

Williamson, J.M., Boettcher, B. and Meister, A. (1982). Intracellular cysteine delivery system that protects against toxicity by promoting glutathione synthesis. Proc. Natl Acad. Sci. USA 79, 6246-6249. 

Originally, for preparation of such conjugates the hydroxyl groups of monomethoxy-PEG (mPEG) were activated with cyanuric chloride, and the resulting compound then coupled with proteins (10). This approach suffers from disadvantages, such as the toxicity of cyanuric chloride and its limited applicability for modification of proteins having essential cysteine or tyrosine residues, as manifested by their loss of activity. 

The selection of an appropriate antioxidant depends on factors such as stability, toxicity, efficiency, odor, taste, compatibility with other ingredients, and distribution phenomena between the two phases. Antioxidants that give protection primarily in the aqueous phase include sodium metabisulfite, ascorbic acid, thioglycerol, and cysteine hydrochloride. Oil-soluble antioxidants include lecithin, propyl gal-late, ascorbyl palmitate, and butylated hydroxytoluene. Vitamin E has also been used, but its virtue as a natural antioxidant has been the subject of some controversy. 

Banki K, Elfarra AA, Lash LH, et al. 1986. Metabolism of S-(2-chloro-l,l,2-trifluoroethyl)-L- cysteine to hydrogen sulfide and the role of hydrogen sulfide in S-(2-chloro-l,l,2-trifluoroethyl)-L-cysteine-induced mitochondrial toxicity. Biochem Boughs Res Caiman 138 707-713. 

The enantiomers of this drug differ in their efficacy and activity, with (D)-penicilla-mine being the enantiomer required for pharmaceutical preparations. The (l)-enantiomer is toxic, and its absorption by the human body is more than the (D)-enantiomer. While both enantiomers of penicillamine are desulfhydrated by (r.)-cysteine desulfhydrase, only the (l)-isomer inhibits the action of this enzyme [2], The reported optical rotation values for (D)-penicillamine are ... 

The second mode of toxicity is postulated to involve the direct interaction of the epidithiodiketopiperazine motif with target proteins, forming mixed disulfides with cysteine residues in various proteins. Gliotoxin, for example, has been demonstrated to form a 1 1 covalent complex with alcohol dehydrogenase [13b, 17]. Epidithiodi-ketopiperazines can also catalyze the formation of disulfide bonds between proxi-mally located cysteine residues in proteins such as in creatine kinase [18]. Recently, epidithiodiketopiperazines have also been implicated in a zinc ejection mechanism, whereby the epidisulfide can shuffle disulfide bonds in the CHI domain of proteins, coordinate to the zinc atoms that are essential to the tertiary structure of that domain, and remove the metal cation [12d, 19],... 

The answer is c. (Hardman, pp 632-633.) Nausea, vomiting, abdominal pain, and diarrhea are early signs of the severe liver toxicity caused by high levels of acetaminophen other symptoms of acetaminophen toxicity include dizziness, excitement, and disorientation. N-acetyl-L-cysteine is the appropriate treatment for acetaminophen overdose. 

The germanium derivative of cysteine Ge[SCH2CH(NH2)COOH]4 shows low toxicity in acute (3402 mg kg-1), subacute and chronic experiments53. No teratogenic effects were noticed in rats and mice after subcutaneous administration of the compound54. 

Dermal toxicity due to JP-8 may also be attributed to increased free radical formation that may be involved in the development of skin sensitization [45], Following dermal exposure to JP-8, increasing levels of oxidative species are observed [46], In vitro studies with rat lung epithelial cells demonstrated that JP-8-induced cell death is inhibited by exogenous glutathione or the thiol-containing antioxidant N-acetyl-cysteine... 

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