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- Title
Atorvastatin and Vitamin E Accelerates NASH Resolution by Dietary Intervention in a Preclinical Guinea Pig Model.
- Authors
Klaebel, Julie Hviid; Skjødt, Mia; Skat-Rørdam, Josephine; Rakipovski, Günaj; Ipsen, David H.; Schou-Pedersen, Anne Marie V.; Lykkesfeldt, Jens; Tveden-Nyborg, Pernille
- Abstract
Despite affecting millions of patients worldwide, no pharmacological treatment has yet proved effective against non-alcoholic steatohepatitis (NASH) induced liver fibrosis. Current guidelines recommend lifestyle modifications including reductions in dietary energy intake. Recently, therapy with atorvastatin and vitamin E (vitE) has been recommended, although clinical studies on the resolution of hepatic fibrosis are inconclusive. Targeting NASH-induced hepatic end-points, this study evaluated the effects of atorvastatin and vitE alone or in combination with a dietary intervention in the guinea pig NASH model. Guinea pigs (n = 72) received 20 weeks of high fat feeding before allocating to four groups: continued HF feeding (HF), HF diet with atorvastatin and vitE (HF+), low-fat diet (LF) and low-fat with atorvastatin and vitE (LF+), for four or eight weeks of intervention. Both LF and LF+ decreased liver weight, cholesterol and plasma dyslipidemia. LF+ further improved hepatic histopathological hallmarks (p < 0.05), liver injury markers aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (p < 0.05) and reduced the expression of target genes of hepatic inflammation and fibrosis (p < 0.05), underlining an increased effect on NASH resolution in this group. Collectively, the data support an overall beneficial effect of diet change, and indicate that atorvastatin and vitE therapy combined with a diet change act synergistically in improving NASH-induced endpoints.
- Subjects
LIVER injuries; INFLAMMATION prevention; ANIMAL experimentation; BIOMARKERS; BIOLOGICAL models; CHOLESTEROL; COMBINED modality therapy; DIET therapy; FATTY liver; FAT content of food; GENE expression; HISTOLOGY; HYPERLIPIDEMIA; LIVER; LOW-fat diet; SWINE; VITAMIN E; FIBROSIS; TREATMENT effectiveness; DISEASE remission; ATORVASTATIN; DESCRIPTIVE statistics; PHARMACODYNAMICS; EVALUATION
- Publication
Nutrients, 2019, Vol 11, Issue 11, p2834
- ISSN
2072-6643
- Publication type
Article
- DOI
10.3390/nu11112834