Abstract
Background Hepatic steatosis is the most common type of chronic liver disease and is considered an established risk factor of major chronic diseases. Purpose The present study aimed to investigate the effect of Dunaliella salina, a microalga and its isolated zeaxanthin on age-related hepatic steatosis as well as their underling mechanism. Study Design. Age-related hepatic steatosis was induced in rats by intraperitoneal injection of D-galactose (200 mg/kg/day) for eight consecutive weeks. D. salina biomass (BDS; 450 mg/kg), its polar fraction (PDS; 30 mg/kg), carotenoid fraction (CDS; 30 mg/kg), and isolated zeaxanthin heneicosylate (ZH; 250 μg/kg) were orally administered to D-galactose treated rats for two weeks. Methods Blood samples were collected 24 hours after the last dose of D. salina treatments, animals were sacrificed, and liver tissues were isolated. Sera as well as hepatic tissue homogenates were used for further investigations. Liver tissues were also used for histopathological and immunohistochemical examinations. A computed virtual docking study for the biologically active candidates was performed to confirm the proposed mechanism of action. Results Oral treatment of D-galactose-injected rats with BDS, PDS, CDS, or ZH ameliorated the serum hepatic function parameters as well as serum levels of adiponectin, apolipoprotein B 100, and insulin. Furthermore, D. salina decreased the hepatic lipid contents, redox status biomarkers, inflammatory cytokine, and showing antiapoptotic properties. Molecular docking of β-carotene and zeaxanthin on various receptors involved in the pathophysiological cascade of steatosis highlighted the possible mechanism underlying the observed therapeutic effect. Conclusion D. salina carotenoids have beneficial effect on age-related hepatic steatosis in senescence rats through the regulation of redox status, inflammatory indices, and apoptotic biomarkers.
Highlights
Nonalcoholic fatty liver disease (NAFLD), a disease that is strictly linked to obesity and insulin resistance (IR), is characterized by hyperinsulinaemia, hypertriglyceridemia, and fatty infiltration of the liver, which is known as hepatic steatosis [1]
Its incidence is more prevalent in older populations, and it varies from simple liver steatosis, through nonalcoholic steatohepatitis (NASH) to advanced fibrosis, cirrhosis, and hepatocellular carcinoma. ese three pathologic conditions are accompanied with elevated prevalence and incidence of cardiovascular disease and diabetes mellitus [2]
It has been previously proposed that aging processes may induce hepatic steatosis via various mechanisms, the most important of which are adipose tissue dysfunction, impaired autophagy, and redox status [3]
Summary
Nonalcoholic fatty liver disease (NAFLD), a disease that is strictly linked to obesity and insulin resistance (IR), is characterized by hyperinsulinaemia, hypertriglyceridemia, and fatty infiltration of the liver, which is known as hepatic steatosis [1]. It has been previously proposed that aging processes may induce hepatic steatosis via various mechanisms, the most important of which are adipose tissue dysfunction, impaired autophagy, and redox status [3]. E present study aimed to investigate the effect of Dunaliella salina, a microalga and its isolated zeaxanthin on age-related hepatic steatosis as well as their underling mechanism. Age-related hepatic steatosis was induced in rats by intraperitoneal injection of D-galactose (200 mg/kg/day) for eight consecutive weeks. D. salina biomass (BDS; 450 mg/kg), its polar fraction (PDS; 30 mg/kg), carotenoid fraction (CDS; 30 mg/kg), and isolated zeaxanthin heneicosylate (ZH; 250 μg/kg) were orally administered to D-galactose treated rats for two weeks. D. salina carotenoids have beneficial effect on age-related hepatic steatosis in senescence rats through the regulation of redox status, inflammatory indices, and apoptotic biomarkers
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