Ornithine aspartate and vitamin-E combination has beneficial effects on cardiovascular risk factors in an animal model of nonalcoholic fatty liver disease in rats

Abstract

Cardiovascular (CV) disease is the main cause of death in nonalcoholic fatty liver disease (NAFLD), a clinical condition without any approved pharmacological therapy. Thus, we investigated the effects of ornithine aspartate (LOLA) and/or Vitamin E (VitE) on CV parameters in a steatohepatitis experimental model. Adult Sprague Dawley rats were randomly assigned (10 animals each) and treated from 16 to 28 weeks with gavage as follows: controls (standard diet plus distilled water (DW)), NAFLD (high-fat choline-deficient diet (HFCD) plus DW), NAFLD+LOLA (HFCD plus LOLA (200 mg/kg/day)), NAFLD+VitE (HFCD plus VitE (150 mg twice a week)) or NAFLD+LOLA+VitE in the same doses. Atherogenic ratios were higher in NAFLD when compared with NAFLD+LOLA+VitE and controls (p < 0.05). Serum concentration of IL-1β, IL-6, TNF-α, MCP-1, e-selectin, ICAM-1, and PAI-1 were not different in intervention groups and controls (p > 0.05). NAFLD+LOLA decreased miR-122, miR-33a, and miR-186 (p < 0.05, for all) in relation to NAFLD. NAFLD+LOLA+VitE decreased miR-122, miR-33a and miR-186, and increased miR-126 (p < 0.05, for all) in comparison to NAFLD and NAFLD+VitE. NAFLD+LOLA and NAFLD+LOLA+VitE prevented liver collagen deposition (p = 0.006) in comparison to NAFLD. Normal cardiac fibers (size and shape) were lower in NAFLD in relation to the others; and the inverse was reported for the percentage of regular hypertrophic cardiomyocytes. NAFLD+LOLA+VitE promoted a significant improvement in atherogenic dyslipidemia, liver fibrosis, and paracrine signaling of lipid metabolism and endothelial dysfunction. This association should be further explored in the treatment of NAFLD-associated CV risk factors.