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Toxicity

About: Toxicity is a research topic. Over the lifetime, 24530 publications have been published within this topic receiving 631315 citations.


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Journal ArticleDOI
TL;DR: Biodistribution experiment showed that TiO(2) mainly retained in the liver, spleen, kidneys, and lung tissues, which indicated thatTiO( 2) particles could be transported to other tissues and organs after uptake by gastrointestinal tract.

1,024 citations

Journal ArticleDOI
TL;DR: The results indicate that AMI-25 is a fully biocompatible potential contrast agent for MR and bioavailability similar to that of commercially available IV iron preparations within 7 days.
Abstract: The pharmacokinetics (distribution, metabolism, bioavailability, excretion) and toxicity (acute and subacute toxicity, mutagenicity) of a superparamagnetic iron oxide preparation (AMI-25), currently used in clinical trials, were evaluated by 59Fe radiotracer studies, measurements of relaxation times, the ability to reverse iron deficiency anemia, histologic examination, and laboratory parameters. One hour after administration of AMI-25 to rats (18 mumol Fe/kg; 1 mg Fe/kg), 82.6 +/- 0.3% of the administered dose was sequestered in the liver and 6.2 +/- 7.6% in the spleen. Peak concentrations of 59Fe were found in liver after 2 hr and in the spleen after 4 hr. 59Fe slowly cleared from liver (half-life, 3 days) and spleen (half-life, 4 days) and was incorporated into hemoglobin of erythrocytes in a time-dependent fashion. The half-time of the T2 effect on liver and spleen (24-48 hr) was shorter than the 59Fe clearance, indicating metabolism of AMI-25 into other forms of iron. IV administration of AMI-25 (30 mg Fe/kg) corrected iron-deficiency anemia and showed bioavailability similar to that of commercially available IV iron preparations within 7 days. No acute or subacute toxic effects were detected by histologic or serologic studies in rats or beagle dogs who received a total of 3000 mumol Fe/kg, 150 times the dose proposed for MR imaging of the liver. Our results indicate that AMI-25 is a fully biocompatible potential contrast agent for MR.

1,014 citations

Journal ArticleDOI
TL;DR: The current knowledge regarding potential dietary flavonoid/phenolic-induced toxicity concerns, including their pro-oxidant activity, mitochondrial toxicity (potential apoptosis-inducing properties), and interactions with drug-metabolizing enzymes are summarized.

1,001 citations

Journal ArticleDOI
TL;DR: The recent finding that NADPH oxidase knockout mice were equally sensitive to acetaminophen and had equal nitration of tyrosine suggests that the superoxide is not from the activation of Kupffer cells.
Abstract: The analgesic acetaminophen causes a potentially fatal, hepatic centrilobular necrosis when taken in overdose. The initial phases of toxicity were described in Dr. Gillette's laboratory in the 1970s. These findings indicated that acetaminophen was metabolically activated by cytochrome P450 enzymes to a reactive metabolite that depleted glutathione (GSH) and covalently bound to protein. It was shown that repletion of GSH prevented the toxicity. This finding led to the development of the currently used antidote N-acetylcysteine. The reactive metabolite was subsequently identified to be N-acetyl-p-benzoquinone imine (NAPQI). Although covalent binding has been shown to be an excellent correlate of toxicity, a number of other events have been shown to occur and are likely important in the initiation and repair of toxicity. Recent data have shown that nitrated tyrosine residues as well as acetaminophen adducts occur in the necrotic cells following toxic doses of acetaminophen. Nitrotyrosine was postulated to be mediated by peroxynitrite, a reactive nitrogen species formed by the very rapid reaction of superoxide and nitric oxide (NO). Peroxynitrite is normally detoxified by GSH, which is depleted in acetaminophen toxicity. NO synthesis (serum nitrate plus nitrite) was dramatically increased following acetaminophen. In inducible nitric oxide synthase (iNOS) knockout mice, acetaminophen did not increase NO synthesis or tyrosine nitration; however, histological evidence indicated no difference in toxicity. Acetaminophen did not cause hepatic lipid peroxidation in wild-type mice but did cause lipid peroxidation in iNOS knockout mice. These data suggest that NO may play a role in controlling lipid peroxidation and that reactive nitrogen/oxygen species may be important in toxicity. The source of the superoxide has not been identified, but our recent finding that NADPH oxidase knockout mice were equally sensitive to acetaminophen and had equal nitration of tyrosine suggests that the superoxide is not from the activation of Kupffer cells. It was postulated that NAPQI-mediated mitochondrial injury may be the source of the superoxide. In addition, the significance of cytokines and chemokines in the development of toxicity and repair processes has been demonstrated by several recent studies. IL-1beta is increased early in acetaminophen toxicity and may be important in iNOS induction. Other cytokines, such as IL-10, macrophage inhibitory protein-2 (MIP-2), and monocyte chemoattractant protein-1 (MCP-1), appear to be involved in hepatocyte repair and the regulation of proinflammatory cytokines.

984 citations

Journal ArticleDOI
TL;DR: The toxicity of zinc oxide to bacteria was related to the generation of reactive oxygen species and to the induction of apoptosis, and these effects were differentially greater in human myeloblastic leukemia cells (HL60) than normal peripheral blood mononuclear cells.

910 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
20243
20233,860
20226,839
20211,108
2020971
2019910