Research Article Details
| Article ID: | A21512 |
| PMID: | 25265201 |
| Source: | Nanotoxicology |
| Title: | Intratracheal exposure to multi-walled carbon nanotubes induces a nonalcoholic steatohepatitis-like phenotype in C57BL/6J mice. |
| Abstract: | The effects of multi-walled carbon nanotubes (MWCNTs) exposure have garnered great interest in the field of public health, due to the high aspect ratio of MWCNTs. Because of worldwide increases in obesity prevalence, nonalcoholic fatty liver disease (NAFLD) is now the most common prevalent liver disease and is considered to be a component of metabolic syndrome, which is a cluster of disorders that also includes dyslipidemia, diabetes mellitus, arteriosclerosis, and hypertension. Exposure to MWCNTs is known to be a risk factor for lung and cardiovascular diseases, but its effect on NAFLD is unknown. In this study, we investigated the effects of intratracheal exposure of two different types of MWCNTs, namely, pristine multi-walled carbon nanotubes (PMWCNTs) and acid-treated multi-walled carbon nanotubes (TMWCNTs), on liver pathogenesis. Direct instillation of a test material into the lungs has been employed as a quantitatively reliable alternative method of inhalation exposure. The 10% weight loss dose was assessed in three months of subchronic study and is defined here as the maximum tolerated dose (MTD) of PMWCNTs and TMWCNTs; by this metric, MTD for a 1-year exposure of MWCNTs was determined to be 0.1 mg/mouse. Mice exposed to PMWCNTs and TMWCNTs for one year developed a nonalcoholic steatohepatitis (NASH)-like phenotype, characterized by inflammation, hepatic steatosis, and fibrosis. Furthermore, PMWCNTs induced a more severe NASH-like phenotype than TMWCNTs, which was related to consistent up-regulation of interleukin (IL)-6 and plasminogen activator inhibitor (PAI)-1. Impaired cholesterol homeostasis, overexpression of NF-κBp65, and suppression of peroxisome proliferator-activated receptor gamma (PPARγ) in the liver were also observed. |
| DOI: | 10.3109/17435390.2014.963186 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S08 | Lifestyle measures | Lifestyle intervention; weight loss; diet adaptation; dietary interventions; lifestyle modifications; Exercise | -- | -- | Details |
| S03 | Anti-fibrosis | fibrosis | Angiotensin Receptor Blocker (ARB); CCR2/CCR5 antagonist; Thyroid receptor β agonist; PEGylated human FGF21 analogue; Monoclonal antibody to lysyl oxidase-like 2 (LOXL2); Galectin-3 inhibitor; FGF19 variant | Losartan; Cenicriviroc; VK-2809; MGL-3196; Pegbelfermin; Simtuzumab; GR-MD-02; NGM282 | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I05 | 9352 | Type 2 diabetes mellitus | A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 | disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus | Details |
| I07 | 1936 | Arteriosclerosis | Build-up of fatty material and calcium deposition in the arterial wall resulting in partial or complete occlusion of the arterial lumen.https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&ns=ncit&code=C35768 | disease of anatomical entity/cardiovascular system disease/ vascular disease/ artery disease | Details |
| I12 | 10763 | Hypertension | An artery disease characterized by chronic elevated blood pressure in the arteries. https://en.wikipedia.org/wiki/Hypertension, https://www.ncbi.nlm.nih.gov/pubmed/24352797 | disease of anatomical entity/ cardiovascular system disease/vascular disease/ artery disease | Details |
| I13 | 3146 | Lipid metabolism disorder | An inherited metabolic disorder that involves the creation and degradation of lipids. http://en.wikipedia.org/wiki/Lipid_metabolism | disease of metabolism/ inherited metabolic disorder | Details |
| I14 | 9970 | Obesity | An overnutrition that is characterized by excess body fat, traditionally defined as an elevated ratio of weight to height (specifically 30 kilograms per meter squared), has_material_basis_in a multifactorial etiology related to excess nutrition intake, decreased caloric utilization, and genetic susceptibility, and possibly medications and certain disorders of metabolism, endocrine function, and mental illness. https://en.wikipedia.org/wiki/Obesity | disease of metabolism/acquired metabolic disease/ nutrition disease/overnutrition | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D080 | Citrulline | Chemical drug | DB00155 | -- | -- | Under clinical trials | Details |
| D579 | Emfilermin | Miscellany | -- | adipocytes | Enhance lipid metabolism | Under investigation | Details |
| D010 | Amoxicillin | Chemical drug | DB01060 | -- | -- | Under clinical trials | Details |
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |