Omega-3 polyunsaturated fatty acid and ursodeoxycholic acid have an additive effect in attenuating diet-induced nonalcoholic steatohepatitis in mice
| Autor: | Ja Kyung Kim, Junjeong Choi, Jung Il Lee, Su Yeon Lee, Hye Young Chang, Kwan Sik Lee, Dong Ki Lee |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Male
medicine.medical_specialty Cholagogues and Choleretics Cirrhosis Clinical Biochemistry Inflammation Diet High-Fat Biochemistry chemistry.chemical_compound Fibrosis Non-alcoholic Fatty Liver Disease Internal medicine Fatty Acids Omega-3 medicine Animals Molecular Biology chemistry.chemical_classification Triglyceride biology business.industry Ursodeoxycholic Acid Drug Synergism medicine.disease Ursodeoxycholic acid Nitric oxide synthase Mice Inbred C57BL Endocrinology chemistry Liver biology.protein Molecular Medicine Original Article Steatosis medicine.symptom business medicine.drug Polyunsaturated fatty acid |
| Zdroj: | Experimental & Molecular Medicine |
| ISSN: | 2092-6413 1226-3613 |
| Popis: | Nonalcoholic steatohepatitis (NASH) can progress into liver cirrhosis; however, no definite treatment is available. Omega-3 polyunsaturated fatty acid (omega-3) has been reported to alleviate experimental NASH, although its beneficial effect was not evident when tested clinically. Thus, this study aimed to investigate the additive effect of omega-3 and ursodeoxycholic acid (UDCA) on diet-induced NASH in mice. C57BL/6 mice were given a high-fat diet (HFD) for 24 weeks, at which point the mice were divided into three groups and fed HFD alone, HFD with omega-3 or HFD with omega-3 in combination with UDCA for another 24 weeks. Feeding mice an HFD and administering omega-3 improved histologically assessed liver fibrosis, and UDCA in combination with omega-3 further attenuated this disease. The assessment of collagen α1(I) expression agreed with the histological evaluation. Omega-3 in combination with UDCA resulted in a significant attenuation of inflammation whereas administering omega-3 alone failed to improve histologically assessed liver inflammation. Quantitative analysis of tumor necrosis factor α showed an additive effect of omega-3 and UDCA on liver inflammation. HFD-induced hepatic triglyceride accumulation was attenuated by omega-3 and adding UDCA accentuated this effect. In accordance with this result, the expression of sterol regulatory binding protein-1c decreased after omega-3 administration and adding UDCA further diminished SREBP-1c expression. The expression of inducible nitric oxide synthase (iNOS), which may reflect oxidative stress-induced tissue damage, was suppressed by omega-3 administration and adding UDCA further attenuated iNOS expression. These results demonstrated an additive effect of omega-3 and UDCA for alleviating fibrosis, inflammation and steatosis in diet-induced NASH. |
| Databáze: | OpenAIRE |
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