Manganese is absorbed mainly via ingestion, but can also be inhaled. It binds to alpha-2-macroglobulin, albumin, or transferrin in the plasma and is distributed to the brain and all other mammalian tissues, though it tends to accumulate more in the liver, pancreas, and kidney. Manganese is capable of existing in a number of oxidation states and is believed to undergo changes in oxidation state within the body. Manganese oxidation state can influence tissue toxicokinetic behavior, and possibly toxicity. Manganese is excreted primarily in the faeces. (L228)
Manganese is a cellular toxicant that can impair transport systems, enzyme activities, and receptor functions. It primarily targets the central nervous system, particularily the globus pallidus of the basal ganglia. It is believed that the manganese ion, Mn(II), enhances the autoxidation or turnover of various intracellular catecholamines, leading to increased production of free radicals, reactive oxygen species, and other cytotoxic metabolites, along with a depletion of cellular antioxidant defense mechanisms, leading to oxidative damage and selective destruction of dopaminergic neurons. In addition to dopamine, manganese is thought to perturbations other neurotransmitters, such as GABA and glutamate. In order to produce oxidative damage, manganese must first overwhelm the antioxidant enzyme manganese superoxide dismutase. The neurotoxicity of Mn(II) has also been linked to its ability to substitute for Ca(II) under physiological conditions. It can enter mitochondria via the calcium uniporter and inhibit mitochondrial oxidative phosphorylation. It may also inhibit the efflux of Ca(II), which can result in a loss of mitochondrial membrane integrity. Mn(II) has been shown to inhibit mitochondrial aconitase activity to a significant level, altering amino acid metabolism and cellular iron homeostasis. (L228)
来源:Toxin and Toxin Target Database (T3DB)
毒理性
致癌物分类
对人类无致癌性(未列入国际癌症研究机构IARC清单)。
No indication of carcinogenicity to humans (not listed by IARC).
Manganese mainly affects the nervous system and may cause behavioral changes and other nervous system effects, which include movements that may become slow and clumsy. This combination of symptoms when sufficiently severe is referred to as “manganism”. (L228)
来源:Toxin and Toxin Target Database (T3DB)
毒理性
暴露途径
该物质可以通过吸入其气溶胶和通过摄入被身体吸收。
The substance can be absorbed into the body by inhalation of its aerosol and by ingestion.
来源:ILO-WHO International Chemical Safety Cards (ICSCs)
Chemokine receptor anagonists and methods of use therefor
申请人:Millennium Pharmaceuticals, Inc.
公开号:US20020169155A1
公开(公告)日:2002-11-14
Disclosed are novel compounds and a method of treating a disease associated with aberrant leukocyte recruitment and/or activation. The method comprises administering to a subject in need an effective amount of a compound represented by:
1
or physiologically acceptable salt thereof.
The invention provides a method of preparing a sirtuin complex. The invention also provides a method of detecting a sirtuin in a sample comprising use of the aforesaid sirtuin complex.
4-BENZIMIDAZOL-2-YL-PYRIDAZINE-3-ONE-DERIVATIVES, PRODUCTION AND USE THEREOF IN MEDICAMENTS
申请人:SCHOENAFINGER Karl
公开号:US20070072866A1
公开(公告)日:2007-03-29
The present invention relates to kinase inhibitor compounds and derivatives thereof as well as compositions comprising them for the treatment of neurological disorders such as Alzheimers' disease, Parkinsons' disease, obesity, hypertension and the like. These pyridazinone derivatives particularly inhibit the metabolic activity of glycogen synthase kinase —3β (GSK-3β) which is believed to cause the neurodegeneration that results in these diseases.
CHEMOKINE RECEPTOR ANTAGONISTS AND METHODS OF USE THEREFOR
申请人:——
公开号:US20020119973A1
公开(公告)日:2002-08-29
Disclosed are novel compounds and a method of treating a disease associated with aberrant leukocyte recruitment and/or activation. The method comprises administering to a subject in need an effective amount of a compound represented by:
1
and physiologically acceptable salts thereof.
2
Chemokine receptor antagonists and methods of use therefor
申请人:Millennium Pharmaceuticals, Inc.
公开号:US06509346B2
公开(公告)日:2003-01-21
Disclosed are novel compounds and a method of treating a disease associated with aberrant leukocyte recruitment and/or activation. The method comprises administering to a subject in need an effective amount of a compound represented by:
and physiologically acceptable salts thereof.