虾青素改善四氯化碳诱导的大鼠肝损伤和氧化应激
Astaxanthin Ameliorates Hepatic Damage and Oxidative Stress in Carbon Tetrachloride-administered Rats.
作者信息
Islam Md Ariful, Al Mamun Md Abdullah, Faruk Md, Ul Islam Md Tauhid, Rahman Md Mizanur, Alam Mohammad Nazmul, Rahman A F M Towheedur, Reza Hasan Mahmud, Alam Md Ashraful
机构信息
Department of Pharmaceutical Sciences, North South University, Dhaka 1229, Bangladesh.
出版信息
Pharmacognosy Res. 2017 Dec;9(Suppl 1):S84-S91. doi: 10.4103/pr.pr_26_17.
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 (CCl)-treated rats.
MATERIALS AND METHODS
Female Long-Evans rats were administered with CCl 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 CCl administration in rats increased plasma AST, ALT, and ALP activities which were normalized by astaxanthin treatment. Moreover, CCl 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 CCl-administered rats. Astaxanthin treatment also restored the CAT and SOD activities and lowered MPO activity in CCl-administered rats. Histological assessment also revealed that the astaxanthin prevented the inflammatory cells infiltration, decreased free iron deposition, and fibrosis in liver of CCl-administered rats.
CONCLUSION
These results suggest that astaxanthin protects liver damage induced by CCl by inhibiting lipid peroxidation and stimulating the cellular antioxidant system.
SUMMARY
Carbon tetrachloride (CCl) administration increased oxidative stress-mediated hepatic damage and inflammation in ratsAstaxanthin, a potent antioxidant, prevents oxidative stress and inflammatory cells infiltration in CCl-administered ratsAstaxanthin also ameliorated the progression of hepatic fibrosis in CCl-administered rats. 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.
背景
虾青素属于具有强大抗氧化特性的类胡萝卜素类。本研究旨在评估虾青素对四氯化碳（CCl）处理的大鼠的肝脏保护作用。
材料与方法
雌性长 Evans 大鼠每周口服 CCl（1 ml/kg）两次，共 2 周，并每天用虾青素（10 mg/kg）处理 2 周。从每组中分离血浆样本，分析丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）和碱性磷酸酶活性。测量氧化应激参数，如丙二醛（MDA）、一氧化氮（NO）和晚期蛋白质氧化产物（APOP）。还分析了血浆和肝组织中的几种酶功能，如髓过氧化物酶（MPO）、超氧化物歧化酶（SOD）和过氧化氢酶（CAT）活性。此外，通过肝组织的组织学染色确认炎症和组织纤维化。
结果
本研究表明，给大鼠施用 CCl 会增加血浆 AST、ALT 和 ALP 活性，而虾青素处理可使其恢复正常。此外，与对照大鼠相比，施用 CCl 会增加血浆和组织中的 MDA、NO 和 APOP 水平。虾青素还使施用 CCl 的大鼠的这些参数显著降低。虾青素处理还恢复了施用 CCl 的大鼠的 CAT 和 SOD 活性，并降低了 MPO 活性。组织学评估还显示，虾青素可防止施用 CCl 的大鼠肝脏中的炎性细胞浸润、减少游离铁沉积并减轻纤维化。
结论
这些结果表明，虾青素通过抑制脂质过氧化和刺激细胞抗氧化系统来保护 CCl 诱导的肝损伤。
总结
施用四氯化碳（CCl）会增加大鼠氧化应激介导的肝损伤和炎症
虾青素是一种有效的抗氧化剂，可防止施用 CCl 的大鼠发生氧化应激和炎性细胞浸润
虾青素还改善了施用 CCl 的大鼠肝纤维化的进展。APOP：晚期蛋白质氧化产物；AST：天冬氨酸转氨酶；ALT：丙氨酸转氨酶；ALP：碱性磷酸酶；CAT：过氧化氢酶；CCl4：四氯化碳；CVD：心血管疾病；HSCs：肝星状细胞；H2O2：过氧化氢；MDA：丙二醛；MMP2：基质金属蛋白酶 2；MPO：髓过氧化物酶；NF-κB：核因子κB；NO：一氧化氮；Nrf2：核因子红细胞 2 相关因子 2；·ONOO-：过氧亚硝酸盐；ROS：活性氧；SOD：超氧化物歧化酶；TCA：三氯乙酸；TBA：硫代巴比妥酸；TGF-1：转化生长因子 1，TGF-β：转化生长因子-β；TIMP1：金属蛋白酶组织抑制剂 1；TNF-α：肿瘤坏死因子-α；·CCl3：三氯甲基自由基；CCl3O2-：三氯过氧自由基。
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