Research Article Details
| Article ID: | A43366 |
| PMID: | 31901629 |
| Source: | Environ Res |
| Title: | Global liver proteomic analysis of Wistar rats chronically exposed to low-levels of bisphenol A and S. |
| Abstract: | Exposure to bisphenol A (BPA) and bisphenol S (BPS) has been associated with the development of metabolic disorders, such as obesity, dyslipidemias, and nonalcoholic fatty liver disease. Nonetheless, the associated mechanisms are still not fully understood. BPS is being used with no restrictions to replace BPA, which increases the concern regarding its safety and claims for further investigation on its potential mechanisms of toxicity. The present study aims to access liver molecular disturbances which could be associated with systemic metabolic disorders following exposure to BPA or BPS. Therefore, body weight gain and serum biochemical parameters were measured in male Wistar rats chronically exposed to 50 or 500 µg/kg/day of BPA or BPS, while an extensive evaluation of liver protein expression changes was conducted after exposure to 50 µg/kg/day of both compounds. Exposure to the lowest dose of BPA led to the development of hyperglycemia and hypercholesterolemia, while the BPS lowest dose led to the development of hypertriglyceridemia. Besides, exposure to 500 µg/kg/day of BPS significantly increased body weight gain and LDL-cholesterol levels. Hepatic proteins differentially expressed in BPA and BPS-exposed groups compared to the control group were mostly related to lipid metabolism and synthesis, with upregulation of glucokinase activity-related sequence 1 (1.8-fold in BPA and 2.4-fold in BPS), which is involved in glycerol triglycerides synthesis, and hydroxymethylglutaryl-CoA synthase cytoplasmic (2-fold in BPS), an enzyme involved in mevalonate biosynthesis. Essential mitochondrial proteins of the electron transport chain were upregulated after exposure to both contaminants. Also, BPA and BPS dysregulated expression of liver antioxidant enzymes, which are involved in cellular reactive oxygen species detoxification. Altogether, the results of the present study contribute to expand the scientific understanding of how BPA and BPS lead to the development of metabolic disorders and reinforce the risks associated with exposure to these contaminants. |
| DOI: | 10.1016/j.envres.2019.109080 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S02 | Enhance lipid metabolism | triglyceride-lowering; lipid tolerance; lipid metabolism | 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitor; Decreases intestinal cholesterol absorption; FXR agonist; ACC inhibitor; FAS inhibitor; DGAT2 inhibitor; SCD-1 inhibitor | Atorvastatin; Ezetimibe; Obeticholic Acid; GS-9674; GS-0976; TVB-2640; IONIS-DGAT2rx; Aramchol; | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| 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 |
| 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 |
| 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 | |
|---|---|---|---|---|---|---|---|
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D080 | Citrulline | Chemical drug | DB00155 | -- | -- | Under clinical trials | Details |
| D083 | CLA | Chemical drug | DB01211 | KCNH2; SLCO1B1; SLCO1B3 | -- | Under clinical trials | Details |
| D094 | Cysteamine | Chemical drug | DB00847 | GSS stimulant | Renal drug | Under clinical trials | Details |
| D095 | Cysteamine bitartrate | Chemical drug | DB00847 | -- | -- | Under clinical trials | Details |