Long-term docosahexaenoic acid therapy in a congenic murine model of cystic fibrosis.
We used a congenic C57Bl/6J cystic fibrosis transmembrane conductance regulator (Cftr)(-/-) mouse model, which develops cystic fibrosis (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 killed for histological and lipid analysis after 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 compared with 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.
Beharry
Satti
S
Program in Integrative Biology, The Research Institute, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
Ackerley
Cameron
C
Corey
Mary
M
Kent
Geraldine
G
Heng
Yew-Meng
YM
Christensen
Hilary
H
Luk
Catherine
C
Yantiss
Rhonda K
RK
Nasser
Imad A
IA
Zaman
Munir
M
Freedman
Steven D
SD
Durie
Peter R
PR
D000284:Administration, Oral; D000367:Age Factors; D000818:Animals; D016718:Arachidonic Acid / Q000032:analysis / Q000097:blood; D001652:Bile Ducts / Q000187:drug effects / Q000473:pathology; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D004912:Erythrocytes / Q000737:chemistry; D007082:Ileum / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000473:pathology; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D018181:Mice, Inbred CFTR; D010179:Pancreas / Q000187:drug effects / Q000473:pathology; D011897:Random Allocation; D012469:Salivary Glands / Q000187:drug effects / Q000473:pathology; D016896:Treatment Outcome
D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid