Research Article Details
| Article ID: | A35259 |
| PMID: | 21276150 |
| Source: | Hepatol Res |
| Title: | Pitavastatin inhibits hepatic steatosis and fibrosis in non-alcoholic steatohepatitis model rats. |
| Abstract: | AIM:   Non-alcoholic steatohepatitis (NASH) may progress to liver cirrhosis, and NASH patients with liver cirrhosis are at risk of developing hepatocellular carcinoma. Statins, 3-hydroxy-3-methyglutaryl-coenzyme A reductase inhibitors, are well known to reduce low-density lipoprotein cholesterol and reduce the incidence of coronary heart disease and other major vascular events by anti-inflammatory and antifibrotic effects, and antiproliferative properties in colorectal cancers have also been reported. Recently, statins have been reported to improve hepatic steatosis; however, the effect on fibrosis is controversial. METHODS:   The effects of pitavastatin (one of the strongest statins) were examined using a choline-deficient L-amino acid-defined (CDAA) diet liver fibrosis model. RESULTS:   Pitavastatin significantly attenuated increases in serum aspartate aminotransferase, alanine aminotransferase, hepatic steatosis, oxidative stress, pre-neoplastic lesions (glutathione S-transferase placental form-positive lesions), expression of cytokines, such as tumor necrosis factor-α and transforming growth factor-β1, and the expression of tissue inhibitor of metalloproteinase-1, tissue inhibitor of metalloproteinase-2 and type I procollagen genes followed by attenuating fibrosis of the liver of CDAA-fed rats. CONCLUSION:   These results indicate that pitavastatin may inhibit steatosis, hepatic fibrosis and carcinogenesis in rat model of NASH. |
| DOI: | 10.1111/j.1872-034X.2010.00769.x |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| 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 |
|---|
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D579 | Emfilermin | Miscellany | -- | adipocytes | Enhance lipid metabolism | Under investigation | Details |
| D199 | L-alanine | Chemical drug | DB00160 | KYNU | -- | Failed in clinical trials | Details |
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D075 | Choline | Supplement | DB00122 | PLD2 product of; PLD1 product of | -- | Under clinical trials | Details |
| D277 | Pitavastatin | Chemical drug | DB08860 | HMGCR inhibitor | Enhance lipid metabolism | Failed in clinical trials | Details |
| D349 | Statins | Miscellany | -- | -- | -- | 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 |