Astaxanthin Ameliorates Hepatic Damage and Oxidative Stress in Carbon Tetrachloride-administered Rats

Abstract

Background: Astaxanthin is of carotenoids group which possess strong antioxidant properties. The present study was conducted to evaluate the hepatoprotective effects of astaxanthin in carbon tetrachloride (CCl₄)-treated rats.

Materials and methods: Female Long-Evans rats were administered with CCl₄ orally (1 ml/kg) twice a week for 2 weeks and were treated with astaxanthin (10 mg/kg) every day for 2 weeks. Blood plasma samples were isolated from each group and were analyzed for alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase activities. Oxidative stress parameters such as malondialdehyde (MDA), nitric oxide (NO), and advanced protein oxidation product (APOP) were measured. Several enzyme functions such as myeloperoxidase (MPO), superoxide dismutase (SOD), and catalase (CAT) activities in the plasma and liver tissues were also analyzed. Moreover, inflammation and tissue fibrosis were also confirmed by histological staining of liver tissues.

Results: This investigation revealed that CCl₄ administration in rats increased plasma AST, ALT, and ALP activities which were normalized by astaxanthin treatment. Moreover, CCl₄ administration increased as MDA, NO, and APOP level both in plasma and tissues compared to control rats. Astaxanthin also exhibited a significant reduction of those parameters in CCl₄-administered rats. Astaxanthin treatment also restored the CAT and SOD activities and lowered MPO activity in CCl₄-administered rats. Histological assessment also revealed that the astaxanthin prevented the inflammatory cells infiltration, decreased free iron deposition, and fibrosis in liver of CCl₄-administered rats.

Conclusion: These results suggest that astaxanthin protects liver damage induced by CCl₄ by inhibiting lipid peroxidation and stimulating the cellular antioxidant system.

Summary: Carbon tetrachloride (CCl₄) administration increased oxidative stress-mediated hepatic damage and inflammation in ratsAstaxanthin, a potent antioxidant, prevents oxidative stress and inflammatory cells infiltration in CCl₄-administered ratsAstaxanthin also ameliorated the progression of hepatic fibrosis in CCl₄-administered rats. Abbreviations Used: APOP: Advanced protein oxidation product; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; ALP: Alkaline phosphatase; CAT: Catalase; CCl4: Carbon tetrachloride; CVD: Cardiovascular disease; HSCs: Hepatic stellate cells; H2O2: Hydrogen peroxide; MDA: Malondialdehyde; MMP2: Matrix metalloproteinase2; MPO: Myeloperoxidase; NF-κB: Nuclear factor kappa B; NO: Nitric oxide; Nrf2: Nuclear factor erythroid 2-related factor 2; ·ONOO-: Peroxynitrate; ROS: Reactive oxygen species; SOD: superoxide dismutase; TCA: Trichloroacetic acid; TBA: Thiobarbituric acid; TGF-1: Transforming growth factor 1, TGF-β: Transforming growth factor-β; TIMP1: Tissue inhibitor of metalloproteinase 1; TNF-α: Tumor necrosis factor-alpha;·CCl3: Trichloromethyl free radical; CCl3O2-: Trichloroperoxyl radical.

Keywords: Carbon tetrachloride; fibrosis; inflammation; lipid peroxidation.

Figure 1

Effect of astaxanthin on body weight, food, and water intake in carbon tetrachloride-induced rats. Data are presented as mean ± standard error of mean, n = 6–7 or otherwise stated. Statistical analysis was conducted by one-way analysis of variance followed by Newman–Keuls post hoc test; significance was considered at P < 0.05 in all cases

Figure 2

Effect of astaxanthin on hepatic inflammation and hepatic fibrosis in CCl₄-treated rats. (a and e) Control; (b and f) CCl₄; (c and g) control + astaxanthin; and (d and h) CCl₄ + astaxanthin, (×40). CCl₄: Carbon tetrachloride

Figure 3

Effect of astaxanthin on hepatic iron deposition in CCl₄-treated rats. (a) Control; (b) CCl₄; (c) control + astaxanthin; and (d) CCl₄ + astaxanthin, (×40). CCl₄: Carbon tetrachloride