Title page for etd-0506117-163948


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URN etd-0506117-163948
Author Chih-chiang Wang
Author's Email Address No Public.
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Department Marine Biotechnology and Resources
Year 2016
Semester 2
Degree Ph.D.
Type of Document
Language English
Title The renal-protective effects of active substances from marine photosynthetic bacteria
Date of Defense 2017-01-20
Page Count 119
Keyword
  • diabetic nephropathy
  • oxidative stress
  • LCG
  • chronic kidney disease
  • antioxidants
  • Abstract Chronic kidney disease (CKD) is a major burden worldwide. Oxidative stress and chronic inflammation play pivotal roles in CKD, especially CKD caused by diabetic nephropathy (DN). End-stage renal disease that needs treatment through hemodialysis is most commonly caused via DN. Antioxidants have been shown to be beneficial against DN. However, antioxidants are rarely used in clinical practice, probably due to the extremely high doses needed to achieve therapeutic effects. Therefore, possible side effects and cost limit the use of antioxidants for therapeutic purposes. Recently, a novel compound LCG that displays anti-inflammatory activity was extracted from transformant Rhodobacter sphaeroides. LCG showed less toxicity and more potent anti-oxidative activity than lycopene, an antioxidant widely used as a nutritional supplement. Microbial carotenoids have many advantages over plant carotenoids. Carotenoid extraction from microorganisms is more effective and less expensive process. Fermentation is independent of the weather situation. The mutant strain displayed a 3.5-fold increase in carotenoid content, relative to the wild type.
     The components of LCG were discovered via nuclear magnetic resonance (NMR) studies, these include spheroidenone, methoxyneurosporene, Îľ-carotene, and neurosporene. Interestingly, no irritation response was seen on hamster skins after 30 days of treatment with 0.2% LCG, demonstrating that LCG has good biocompatibility. LCG reduced reactive oxygen species and epithelial–mesenchymal transition markers in H2O2-treated HK2 cells. Using a diabetic mouse model, orally administered LCG (200mg/kg) significantly reduced proteinuria, lowered blood sugar, and reduced insulin resistance after 24 hours. LycogenTM reduced apoptosis in diabetic mice measured via the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay from biopsies of renal tissue. A reduction in apoptosis can attenuate nephron loss and decrease proteinuria. LCG reduced phosphorylation of p38, which is probably how LCG presents an anti-inflammatory effect and reduces EMT. Due to less toxicity and more potent anti-oxidative activity than lycopene, LCG is a potential target for further investigation to confirm the benefits of high dose antioxidants treatment in DN.
    Advisory Committee
  • Chen, Chun-Lin - chair
  • Liu, Wang-ta - co-chair
  • Chang, Li-Yu - co-chair
  • Chang, Chi-I - co-chair
  • Hsu, Jue-Liang - co-chair
  • Lin, Hsiu-Chin - co-chair
  • Pan, Chieh-Yu - co-chair
  • Wang, Hui-Min - co-chair
  • Wen, Zhi-Hong - advisor
  • Files
  • etd-0506117-163948.pdf
  • Indicate in-campus at 99 year and off-campus access at 99 year.
    Date of Submission 2017-06-06

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