Research Article Details
| Article ID: | A20511 |
| PMID: | 25915484 |
| Source: | Curr Drug Targets |
| Title: | Antioxidant Mechanisms in Nonalcoholic Fatty Liver Disease. |
| Abstract: | Nonalcoholic fatty liver disease (NAFLD) represents a broad spectrum of histological abnormalities with clinical presentations ranging from hepatic steatosis to nonalcoholic steatohepatitis (NASH). Some NAFLD patients may progress to cirrhosis and ultimately hepatocellular carcinoma (HCC). Hepatic steatosis, the hallmark of NAFLD, is defined by the accumulation of triglycerides (TGs) in more than 5% of the hepatocytes. NASH is characterized by inflammation along with variable degrees of fibrosis in addition to steatosis. NAFLD has been considered to be the hepatic manifestation of metabolic syndrome (MS), as it is frequently associated with MS conditions such as insulin resistance (IR) and obesity. Hepatic steatosis mainly results from disrupted homeostasis of lipid metabolism in the setting of IR. Although the mechanism underlying the progression from steatosis to NASH is still not fully elucidated, mounting evidence has suggested oxidative stress (OS) to be a key driving force. Elevated OS has been well documented in NAFLD patients. OS can cause direct damages to lipid, protein, and DNA molecules and trigger the inflammatory and fibrogenesis signaling pathways, which promotes the progression from steatosis to NASH. OS may also have various effects on antioxidant defense mechanisms. Overproduced reactive oxygen species (ROS) may directly deplete antioxidant molecules such as glutathione (GSH) and inhibit the activities of antioxidant enzymes such as superoxide dismutase (SOD). ROS may also induce the expression of antioxidant genes to counteract the OS effects. The aim of this review is to discuss oxidative stress and antioxidant mechanisms in NAFLD. |
| DOI: | 10.2174/1389450116666150427155342 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S01 | Improve insulin resistance | insulin sensitizer; insulin resistance; glucose tolerance | Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist | Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide | Details |
| 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 |
| 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 |
| S04 | Anti-oxidative stress | oxidative stress | α-tocopherol: antioxidant | Vitamin E | Details |
| S05 | Anti-inflammatory | inflammatory | Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor | Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; | 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 |
| 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 | |
|---|---|---|---|---|---|---|---|
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D158 | Glutathione | Chemical drug | DB00143 | MGST3; HPGDS; GSTM2; GSTM5; GPX7 cofactor; MGST2; GSS; GSTM1; GSTK1; GSTM3; GSTM4; GPX1 cofactor; GPX2 cofactor; GPX3 cofactor | -- | Under clinical trials | Details |