About: Toxicity is a(n) research topic. Over the lifetime, 24530 publication(s) have been published within this topic receiving 631315 citation(s).
Papers published on a yearly basis
TL;DR: It is of considerable interest that certain inducers of liver microsomal enzymes have recently been used therapeutically for the treatment of hyperbilirubinemia in jaundiced children and for thetreatment of Cushing's syndrome.
Abstract: In increasingly large numbers, drugs, pesticides, herbicides, food additives, and environmental carcinogenic hydrocarbons are being found to stimulate their own metabolism or the metabolism of other compounds. The evidence suggests that foreign chemicals exert this action by increasing the amount of drug-metabolizing enzymes in liver microsomes.Treatment of animals or man with suitable inducers of liver microsomal enzymes accelerates drug metabolism in vivo and alters the duration and intensity of drug action. For instance, barbiturates decrease the anticoagulant activity of coumarin anticoagulants by accelerating their metabolism. This effect requires that the dosage of coumarins be raised to obtain an adequate anticoagulant response, and serious toxicity can result after combined therapy with a coumarin anticoagulant and a stimulator of drug metabolism when the enzyme stimulator is withdrawn and the anticoagulant is continued without an appropriate decrease in dose. The stimulatory effect of drugs on their own metabolism often allows the organism to detoxify drugs more rapidly. This effect has considerable importance when it causes drugs to become less toxic and less effective during prolonged administration. However, if a metabolite has more activity than the parent drug, enzyme induction can enhance the drug's action. Enzyme induction may also be important during chronic exposure to environmental carcinogens, such as 3, 4-benzpyrene. The ability of 3, 4-benzpyrene to stimulate its own metabolism in liver, lung, gastrointestinal tract and skin represents an important mechanism for the detoxification of this substance. Inducers of microsomal enzymes stimulate the metabolism or synthesis of several normal body substrates such as steroid hormones, pyridine nucleotides, cytochromes, and bilirubin. Evidence has accumulated that steroids are normal body substrates of drug-metabolizing enzymes in liver microsomes. Accordingly, treatment of rats with phenobarbital enhances the hydroxylation of androgens, estrogens, glucocorticoids, and progestational steroids by liver microsomes. This effect is paralleled in vivo by enhanced metabolism of steroids to polar metabolites and by a decreased action of steroids such as estradiol, estrone, and progesterone. Recent studies suggest that inducers of liver microsomal enzymes enhance the hydroxylation of steroids in man. Phenobarbital, diphenylhydantoin, and phenylbutazone are examples of drugs that stimulate cortisol hydroxylase activity in guinea pig liver microsomes and enhance the urinary excretion of 6 β-hydroxycortisol in man. Further research is needed to learn whether the stimulatory action of drugs on the metabolism of normal body constituents is harmful or whether it restores a homeostasis that was upset by drug administration. It is of considerable interest that certain inducers of liver microsomal enzymes have recently been used therapeutically for the treatment of hyperbilirubinemia in jaundiced children and for the treatment of Cushing's syndrome. Considerable further work is required to evaluate more completely the effects of liver microsomal enzyme inducers on the metabolism of bilirubin, cortisol, and other normal body constituents in experimental animals and man.
TL;DR: Apo2L may have potent anticancer activity without significant toxicity toward normal tissues, and cooperated synergistically with the chemotherapeutic drugs 5-fluorouracil or CPT-11, causing substantial tumor regression or complete tumor ablation.
Abstract: TNF and Fas ligand induce apoptosis in tumor cells; however, their severe toxicity toward normal tissues hampers their application to cancer therapy. Apo2 ligand (Apo2L, or TRAIL) is a related molecule that triggers tumor cell apoptosis. Apo2L mRNA is expressed in many tissues, suggesting that the ligand may be nontoxic to normal cells. To investigate Apo2L’s therapeutic potential, we generated in bacteria a potently active soluble version of the native human protein. Several normal cell types were resistant in vitro to apoptosis induction by Apo2L. Repeated intravenous injections of Apo2L in nonhuman primates did not cause detectable toxicity to tissues and organs examined. Apo2L exerted cytostatic or cytotoxic effects in vitro on 32 of 39 cell lines from colon, lung, breast, kidney, brain, and skin cancer. Treatment of athymic mice with Apo2L shortly after tumor xenograft injection markedly reduced tumor incidence. Apo2L treatment of mice bearing solid tumors induced tumor cell apoptosis, suppressed tumor progression, and improved survival. Apo2L cooperated synergistically with the chemotherapeutic drugs 5-fluorouracil or CPT-11, causing substantial tumor regression or complete tumor ablation. Thus, Apo2L may have potent anticancer activity without significant toxicity toward normal tissues.
TL;DR: The cytotoxic action of A beta on neurons results from free radical damage to susceptible cells, suggesting that A beta activates a member of this class of enzymes.
Abstract: Amyloid beta protein (A beta) is a 40-43 amino acid peptide that is associated with plaques in the brains of Alzheimer's patients and is cytotoxic to cultured neurons. Using both primary central nervous system cultures and clonal cell lines, it is shown that a number of anti-oxidants protect cells from A beta toxicity, suggesting that at least one pathway to A beta cytotoxicity results in free radical damage. A beta causes increased levels of H2O2 and lipid peroxides to accumulate in cells. The H2O2-degrading enzyme catalase protects cells from A beta toxicity. Clonal cell lines selected for their resistance to A beta toxicity also become resistant to the cytolytic action of H2O2. In addition, A beta induces the activity of NF-kappa B, a transcription factor thought to be regulated by oxidative stress. Finally, A beta-induced H2O2 production and A beta toxicity are blocked by reagents that inhibit flavin oxidases, suggesting that A beta activates a member of this class of enzymes. These results show that the cytotoxic action of A beta on neurons results from free radical damage to susceptible cells.
TL;DR: The microscopic studies demonstrated that nanoparticle-exposed cells at higher doses became abnormal in size, displaying cellular shrinkage, and an acquisition of an irregular shape, which suggested that cytotoxicity of Ag (15, 100 nm) in liver cells is likely to be mediated through oxidative stress.
Abstract: This study was undertaken to address the current deficient knowledge of cellular response to nanosized particle exposure. The study evaluated the acute toxic effects of metal/metal oxide nanoparticles proposed for future use in industrial production methods using the in vitro rat liver derived cell line (BRL 3A). Different sizes of nanoparticles such as silver (Ag; 15, 100 nm), molybdenum (MoO(3); 30, 150 nm), aluminum (Al; 30, 103 nm), iron oxide (Fe(3)O(4); 30, 47 nm), and titanium dioxide (TiO(2); 40 nm) were evaluated for their potential toxicity. We also assessed the toxicity of relatively larger particles of cadmium oxide (CdO; 1 microm), manganese oxide (MnO(2); 1-2 microm), and tungsten (W; 27 microm), to compare the cellular toxic responses with respect to the different sizes of nanoparticles with different core chemical compositions. For toxicity evaluations, cellular morphology, mitochondrial function (MTT assay), membrane leakage of lactate dehydrogenase (LDH assay), reduced glutathione (GSH) levels, reactive oxygen species (ROS), and mitochondrial membrane potential (MMP) were assessed under control and exposed conditions (24h of exposure). Results showed that mitochondrial function decreased significantly in cells exposed to Ag nanoparticles at 5-50 microg/ml. However, Fe(3)O(4), Al, MoO(3) and TiO(2) had no measurable effect at lower doses (10-50 microg/ml), while there was a significant effect at higher levels (100-250 microg/ml). LDH leakage significantly increased in cells exposed to Ag nanoparticles (10-50 microg/ml), while the other nanoparticles tested displayed LDH leakage only at higher doses (100-250 microg/ml). In summary the Ag was highly toxic whereas, MoO(3) moderately toxic and Fe(3)O(4), Al, MnO(2) and W displayed less or no toxicity at the doses tested. The microscopic studies demonstrated that nanoparticle-exposed cells at higher doses became abnormal in size, displaying cellular shrinkage, and an acquisition of an irregular shape. Due to toxicity of silver, further study conducted with reference to its oxidative stress. The results exhibited significant depletion of GSH level, reduced mitochondrial membrane potential and increase in ROS levels, which suggested that cytotoxicity of Ag (15, 100 nm) in liver cells is likely to be mediated through oxidative stress.
27 Oct 1991
Abstract: Essentiality Toxicity Carcinogenicity Lead(Pb) Exposure Toxicokinetics Toxicity Neurologic, Neurobehavioral, and Developmental Effects in Children Mechanisms of Effects on the Developing Nervous System Peripheral Neuropathy Hematologic Effects Renal Toxicity Lead and Gout Effects on Cardiovascular System Immunotoxicity Bone Effects Reproductive Effects Birth Outcomes Carcinogenicity Other Effects Dose Response Treatment Organic Lead Compounds Mercury (Hg) Exposure Disposition and Toxicokinetics Metabolic Transformation Cellular Metabolism Toxicology Biological Indicators Treatment Nickel (Ni) Exposure Toxicokinetics Essentiality Toxicity Nickel Carbonyl Poisoning Dermatitis Indicators of Nickel Toxicity
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