Effects of rosuvastatin and/or β-carotene on non-alcoholic fatty liver in rats

Abstract

The prevalence of non-alcoholic fatty liver disease (NAFLD) has markedly increased, especially in patients exhibit one or more features of the metabolic syndrome. This study investigates the effect of rosuvastatin (RSV) and/or β-carotene (βC) in NAFLD-induced rats. Rats were classified into nine groups; normal (I), NAFLD-induced with high-fat diet (HFD; II), NAFLD switched to regular diet (RD; III), NAFLD-HFD or NAFLD-RD treated with RSV (IV, V), βC (VI, VII) or both RSV+βC (VIII, IX), respectively. After four weeks, rats were sacrificed to obtain serum samples and liver tissues. Liver histology, lipid profile, liver oxidative stress markers, and adipocytokines were measured. Liver sections of rats with NAFLD-HFD revealed steatosis, lose of hepatic architecture, inflammation and hepatocyte vacuolation with high percentage of cell fibrosis. Serum levels of ALT, AST, ALP, gamma glutamyl transferase (GGT) and lipid profile (triglycerides, cholesterol, LDL and VLDL) were significantly increased (P<0.05) compared with normal. Also, hepatic malondialdehyde level and serum leptin, tumor necrosis factor-alpha (TNF-α) and transforming growth factor-β1 (TGF-β1) were increased. Meanwhile, superoxide dismutase (SOD) activity, GSH content in liver, serum HDL and adiponectin were decreased (P<0.05) vs normal. These changes were observed to a lesser extent in NAFLD-RD group. Administration of RSV or/and βC almost improved all previously mentioned parameters. Moreover, hepatic steatosis was decreased and inflammation was markedly ameliorated with reduction of TNF-α and TGF-β. These results were more pronounced in the groups VIII and IX vs each drug alone. In conclusion RSV and βC could be beneficial for the treatment and prevention of NAFLD. Combined RSV with βC is more effective than RSV alone.

Keywords: NAFLD; Oxidative stress; Rosuvastatin; TGF-β1; TNF-α; β-carotene.

Fig. 1

Effect of rosuvastatin and β-carotene alone or in combination on liver functions in NAFLD-induced rats. A; ALT, B; AST, C; ALP, D; GGT. Values are presented as mean ± SEM, (n=8). a; P<0.05 significant difference from normal. b; P<0.05 significant difference from corresponding NAFLD control.

Fig. 2

Effect of rosuvastatin and β-carotene alone or in combination on adipocytokine markers, A; adiponectin, B; leptin, C; TNF-α and D; TGF-β1 in NAFLD-induced rats. Values are presented as mean ± SEM, (n=8). a; P<0.05 significant difference from normal. b; P<0.05 significant difference from corresponding NAFLD control.

Fig. 3

Liver sections from; normal untreated rats, a; ×100; composed of hexagonal or pentagonal lobules with central veins (black arrow) and portal tract (bright green arrow) embedded in connective tissue. Hepatocytes are arranged in trabecules running radiantly from the central vein and are separated by sinusoids (yellow arrow) containing Kuppfer cells, b; ×200; NAFLD-HFD rats, c; showing lost hepatic architecture, formation of fibrous septa (blue arrow) moderate macro 50% (black arrow) and micro (bright green arrow) steatotic changes, many hepatocytes with cytoplasmic vacuoles (yellow arrow), and to a less extent in NAFLD-RD rats, d; RSV-HFD-treated rats, e; showing loss of hepatic architecture 62.5%, macro (black arrow) and micro (yellow arrow) 37.5% steatotic changes, RSV-RD-treated rats, f; showing intact hepatic architecture 75%, large lipid droplets as macro (black arrow) 75% steatotic changes, βC-HFDtreated rats, g; showing partial loss of hepatic architecture 37.5%, macro (black arrow) and micro (yellow arrow) 50% steatotic changes, βC-RD-treated rats, h; showing intact hepatic architecture 75%, micro (yellow arrow) and macro (black arrow) 50% steatotic changes, RSV+βC-HFD-treated rats, i; showing preserved hepatic architecture 62.5%, macro (black arrow) 37.5% steatotic changes, and RSV+βC-RD-treated rats, j; showing normal preserved hepatic architecture 100%, liver appear within normal limit with micro (black arrow) lipid droplets (H&E, × 200).