Research Article Details
| Article ID: | A27416 |
| PMID: | 18422963 |
| Source: | J Gastroenterol Hepatol |
| Title: | Polaprezinc attenuates liver fibrosis in a mouse model of non-alcoholic steatohepatitis. |
| Abstract: | BACKGROUND AND AIM: The effect of polaprezinc, a zinc-carnosine chelate compound, on the development of non-alcoholic steatohepatitis (NASH) was investigated in dietary methionine and choline deficient (MCD) mice. METHODS: Mice were fed the MCD diet with or without polaprezinc (2.2 g/kg diet) for 10 weeks. Liver histopathology, triglyceride and lipid peroxide levels, and the expression of genes linked to fibrosis were then assessed. RESULTS: MCD mice developed steatohepatitis accompanied by mild fibrosis with an increase in lipid peroxidation, hepatic stellate cell (HSC) activation, and the augmented mRNA expression of tumor necrosis factor-alpha, transforming growth factor-beta1 and procollagen alpha1(I). The mRNA expression levels of matrix metalloproteinase (MMP)-2 and tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2 were also enhanced. Histopathologically, polaprezinc supplementation did not influence the development of steatosis but it apparently attenuated fibrosis. Polaprezinc slightly reduced lipid peroxidation and suppressed HSC activation as well as the mRNA expression of pro-inflammatory cytokines. Polaprezinc affected the MCD diet-enhanced expression of TIMP-1 even when administered relatively late. CONCLUSION: These results suggest that polaprezinc attenuates fibrosis in NASH by reducing inflammation and lipid peroxidation and, during a later phase, promoting fibrolysis via the inhibition of TIMP expression in the liver. Further investigation is required to clarify the clinical efficacy of polaprezinc in patients with NASH. |
| DOI: | 10.1111/j.1440-1746.2008.05393.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 |
| 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 | |
|---|---|---|---|---|---|---|---|
| D199 | L-alanine | Chemical drug | DB00160 | KYNU | -- | Failed in clinical trials | Details |
| D075 | Choline | Supplement | DB00122 | PLD2 product of; PLD1 product of | -- | Under clinical trials | Details |
| D395 | Zinc | Chemical drug | DB01593 | PSPH; CCS; HDAC1 cofactor; HDAC4 cofactor; INS; UTRN; ASPA cofactor; TP73 cofactor; A2M; AGT; APOBR; APOE; APOL1; C3; C5; CFB; CFH; CFI; CLU; CP; CPN2; DSP; F12; F13B; FGA; GSN; HBB; HPR; JUP; SELENOP; TTR; VTN | -- | Under clinical trials | Details |
| D590 | Polaprezinc | Chemical drug | -- | Lipid peroxidation inhibitors | Anti-oxidative stress | Under investigation | Details |
| D083 | CLA | Chemical drug | DB01211 | KCNH2; SLCO1B1; SLCO1B3 | -- | Under clinical trials | Details |
| D316 | S-adenosyl-L-methionine | Chemical drug | DB00118 | GNMT cofactor | Antiviral | Under clinical trials | Details |