Submitted on December 22, 2005
Accepted on November 8, 2006
Long-term docosahexaenoic acid therapy in a congenic murine model of cystic fibrosis
Satti A. Beharry1, Cameron Ackerely2, Mary Corey3, Geraldine Kent4, Yew-Meng Heng5, Hilary Christensen5, Catherine Luk6, Rhonda K. Yantiss7, Imad A. Nasser8, Munir Zaman9, Steven D. Freedman9, and Peter R Durie10*
1 Integrative Biology, The Hospital for Sick Children, Toronto, Canada
2 Pathology, The Hospital for Sick Children, United States
3 Population Health Sciences, The Hospital for Sick Children, Toronto, Canada; Public Health Sciences, University of Toronto, Toronto, Canada
4 Laboratory Animal Services, The Hospital for Sick Children, London, Canada; Animal Care and Veterinary Services, University of Western Ontario, London, Canada
5 Pathology, The Hospital for Sick Children, Toronto, Canada
6 Laboratory Animal Services, The Hospital for Sick Children, London, Canada
7 Pathology, Weill Medical College of Cornell University, New York, New York, United States
8 Pathology, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, United States
9 Medicine, Beth Israel Deaconess Medical Center, Boston, United States
10 Integrative Biology, The Hospital for Sick Children, Toronto, Canada; Pediatrics, The Hospital for Sick Children, Toronto, Canada; Pediatrics, University of Toronto, Toronto, Canada
* To whom correspondence should be addressed. E-mail: peter.durie{at}sickkids.ca.
We used a congenic C57Bl/6J Cftr-/- mouse model, which develops CF-like pathology in all organs, to evaluate the short- and long-term therapeutic effects of dietary docosahexaenoic acid (DHA). Thirty-day old Cftr-/- mice and wild type littermates were randomized to receive a liquid diet with or without DHA (40 mg/day). Animals were sacrificed for histological and lipid analysis following 7, 30 and 60 days of therapy. DHA had no significant therapeutic or harmful effect on the lung, pancreas or ileum of the Cftr-/- mice or their wild type littermates. In contrast, dietary DHA resulted in highly significant amelioration of the severity of liver disease in the Cftr-/- mice, primarily a reduction in the degree of peri-portal inflammation. Additionally, these detailed measurements confirm our previous findings, that Cftr-/- mice have significant alterations in the pancreas (except external acinar diameter), ileum, liver, lung and salivary (except sublingual) glands at all ages when compared to their age-matched wild type littermates. In conclusion, inhibition of cytokines and/or eicosanoid metabolism and release of endogenous inhibitors of inflammation by DHA may account for the anti-inflammatory effects in the liver of this congenic murine model of CF. The potential therapeutic benefits of DHA in severe CF-associated liver disease remain to be explored.
