碩士 / 弘光科技大學 / 生物科技研究所 / 100 / In the present study, we aimed at developing liposomal delivery system for Astaxanthin (Ast) targeting in ameliorating lipopolysaccharide (LPS)-induced hepatic and renal damages. We hypothesized that encapsulation of Ast in liposomes might promote the therapeutic potential against experimental animals challenged with LPS. For the preparation of liposomal encapsulated Ast, the egg yolk phospholipids (EPC) and Ast were homogenized with high pressure homogenizer to form spherical particles with diameter of 240 ± 58 nm. The encapsulation efficacy is calculated as 58.06 ± 8.0%. From the zeta potential and field-emission electron scanning microscopy (FE-SEM) analysis, it was suggested that the prepared liposomal Ast could be formed as a stable dispersion in solution. During the in vivo experiment, male Sprague-Dawley rats were pretreated orally with saline, N-acetyl cysteins (NAC200 mg/kg B.W.), Astaxanthin (10 mg/kg B.W.) or liposomal Ast (2, 5 and 10 mg/kg B.W.) for 7 consecutive days. LPS (5 mg/kg B.W.) was introduced intraperitoneally at the 7th day and animals were sacrificed 12 h post-LPS challenge for analysis. Hepatic and renal damages were evaluated by measuring GOT (Glutamic oxaloacetic transaminase), GPT( Glutamic pyruvic transaminase), BUN(Blood urea nitrogen) and CRE (Creatinine) in serum. LPS-induced activation of the inflammatory response was evaluated by measuring the levels of serum NO, TNF-α and IL-6 as well as iNOS protein expression. The tissue levels of lipid peroxidation product(malondialdehyde) and the activities of antioxidant enzymes (SOD, CAT and GSH-Px) were used to assess the extent of involvement of oxidative stress mechanisms.
The challenge of animals with LPS resulted significantly in tissue damages, as evidenced by the activation of inflammatory responses (for example; NO, TNF-α and IL-6 increased 5.7, 4.5 and 2.8 fold, respectively); increase in the level of lipid peroxidation product (hepatic and renal MDA increased 3.2 and 2.5 fold, respectively); decrease in the activities of antioxidant enzymes (tissue SOD activities reduced 1.6-1.8 fold, CAT activities reduced 2.4-2.8 fold and GSH-Px activities reduced 1.2 fold) and enhanced histological injuries as shown in histology, as compared to the control group. Pretreatment of animals with antioxidants (NAC, Ast or liposomal Ast) resulted in the significant protection against LPS challenges. Moreover, liposomal Ast (10 mg/kg B.W.) was demonstrated to be more effective than NAC (200 mg/kg B.W.) or free Ast (10 mg/kg B.W.) in attenuating the LPS-induced tissue injuries (for example; NO decreased as 74.2% v.s. 55.0% v.s. 56.0%; TNF-α decreased as 74.4% v.s.56.8% v.s. 56.1% and IL-6 decreased as 55.2% v.s. 42.5% v.s. 27.8%; hepatic MDA reduced as 62.6% v.s. 55.5% v.s.53.8% and renal MDA reduced as 55.4% v.s.35.1% v.s.31.7%, respectively ). In addition, the effects of liposomal Ast (10 mg/kg B.W.) on increasing the activities of antioxidant enzymes and inhibiting iNOS protein expression are better than NAC or free Ast. In conclusion, the results suggested that liposomal preparation of as Ast provided effective protection via anti-inflammatory and antioxidant mechanisms against LPS-induced tissue damages.
| Identifer | oai:union.ndltd.org:TW/100HKU05111005 |
| Creators | 林湘婷 |
| Contributors | , 喬長誠 教授, 邱駿紘 助理教授 |
| Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
| Language | zh-TW |
| Detected Language | English |
| Type | 學位論文 ; thesis |
| Format | 97 |
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