Atorvastatin and Vitamin E Accelerates NASH Resolution by Dietary Intervention in a Preclinical Guinea Pig Model.

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.

• Authors: Julie Hviid Klaebel, Mia Skjødt, Josephine Skat-Rørdam, Günaj Rakipovski, David H Ipsen, Anne Marie V Schou-Pedersen, Jens Lykkesfeldt, Pernille Tveden-Nyborg
• Journal: Nutrients (Nutrients) Vol. 11 Issue 11 (Nov 19 2019) ISSN: 2072-6643 [Electronic] Switzerland
• PMID: 31752351 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Inflammation Mediators
• Lipids
• Vitamin E
• Atorvastatin
• Aspartate Aminotransferases
• Alanine Transaminase

Topics

• Alanine Transaminase (blood)
• Animals
• Aspartate Aminotransferases (blood)
• Atorvastatin (pharmacology)
• Caloric Restriction
• Combined Modality Therapy
• Female
• Guinea Pigs
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (pharmacology)
• Inflammation Mediators (blood)
• Lipids (blood)
• Liver (drug effects, metabolism, pathology)
• Liver Cirrhosis, Experimental (blood, pathology, therapy)
• Non-alcoholic Fatty Liver Disease (blood, pathology, therapy)
• Time Factors
• Vitamin E (pharmacology)