Date of Award

12-2013

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Program

Biomedical Sciences

Track

Cell Biology and Biochemistry

Research Advisor

Dennis D. Black, M.D.

Committee

B. Keith English, M.D. Richard A. Helms, Pharm.D. Tony N. Marion, Ph.D. P. David Rogers, Pharm.D., Ph.D.

DOI

10.21007/etd.cghs.2013.0320

Comments

One of the most devastating complications affecting infants and children with intestinal failure is parenteral nutrition-associated liver disease (PNALD). PNALD is a progressive disease that can lead to liver failure and death. In many cases, children require liver and small bowel transplantation, prolonged hospitalization and home care. Intravenous infusion of a fish oil emulsion has been shown to be efficacious for the treatment of PNALD. The therapeutic mechanism is unknown, but is thought to occur via anti-inflammatory pathways, as of yet undefined. Fish oil contains omega-3 polyunsaturated long-chain fatty acids (ω3PUFA) that have anti-apoptotic and anti-inflammatory effects. This body of work is focused on my central hypothesis that PNALD is attenuated by ω3PUFA via anti-apoptotic and anti-inflammatory mechanisms. I have used both cultured hepatocytes and macrophages and a preterm neonatal pig model to show that ω3PUFA attenuate both apoptosis and inflammation associated with PNALD. Although there are still many unanswered questions concerning the mechanism of ω3PUFA in the treatment of PNALD, this work supports the efficacy of this novel therapy for treating PNALD.

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