Research Article Details
| Article ID: | A28211 |
| PMID: | 16120375 |
| Source: | Mitochondrion |
| Title: | Mitochondrial injury in the pathogenesis of antiretroviral-induced hepatic steatosis and lactic acidemia. |
| Abstract: | Antiretroviral medications have significantly improved the prognosis of individuals infected with the human immunodeficiency virus (HIV) by maintaining immune integrity and limiting the impact of opportunistic infections. However, these benefits have not come without a price as long-term complications of therapy are increasingly recognized as significant causes of morbidity and mortality. Many of these complications are thought to be mediated through mitochondrial injury, which appears to be the result of nucleoside analogue toxicity. A syndrome of fatty liver (steatosis) with lactic acidosis represents the most fulminant presentation of such antiretroviral toxicity, though milder variants of hepatic steatosis with or without lactate elevations have also been described in HIV-seropositive individuals. The spectrum of hepatic steatosis and hyperlactatemia is likely multifactorial and may share some features with non-alcoholic fatty liver disease (NAFLD), which is the hepatic component of the metabolic syndrome described in the general population. As antiretrovirals are also known to contribute to metabolic syndrome components including insulin resistance, hypertriglyceridemia, and central adiposity, the possibility of common pathophysiologic mechanisms underlying NAFLD and antiretroviral-associated fatty liver seem likely. However, lactate elevations are not a component of NAFLD, suggesting other factors must also be involved. A review follows which details the role of mitochondrial damage in hepatic steatosis among HIV-infected individuals and the general population, as well as the association of this damage to the pathogenesis of hyperlactatemia. |
| DOI: | 10.1016/j.mito.2004.06.011 |
| 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 |
| 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 |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D080 | Citrulline | Chemical drug | DB00155 | -- | -- | Under clinical trials | Details |
| D545 | Pig placenta extract | Biological extract | -- | -- | -- | Under clinical trials | Details |
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |