Reduction of hepatocellular injury after common bile duct ligation using omega-3 fatty acids.
OBJECTIVE
Bile duct obstruction and subsequent cholestasis produces hepatocellular injury and an inflammatory response. Fatty acid constitution of cell membranes plays a major role in the inflammatory cascade. Omega-3 fatty acids are antiinflammatory. We proposed that omega-3 fatty acid supplementation would reduce hepatocellular damage and cell death in a model of murine common bile duct ligation.


METHODS
Mice underwent bile duct ligation and were administered either control soy diet (omega-6) or Menhaden diet (omega-3), and parameters of liver injury were measured at postoperative days 1, 4, and 8. Serum was analyzed for liver function tests. Liver tissue was scored for histologic necrosis and inflammation, and apoptosis was qualitatively measured.


RESULTS
At day 8, comparing control and Menhaden, liver function tests were not significantly different. The H&E slides were analyzed and scored. At day 4, the mean necrosis scores for the Menhaden-fed group was 0.01 +/- 0.028 and 0.46 +/- 0.108 for the soy-fed group (P = .001) and at day 8, 0.420 +/- 0.107 and 1.22 +/- 0.132 (P < .001). The mean portal inflammation score for day 4 Menhaden-fed and soy-fed mice was 1.40 +/- 0.245 for both groups (P = 1.00) and for day 8, 1.80 +/- 0.200 and 2.80 +/- 0.200 (P = .008). At day 1, the median terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling scores of the Menhaden vs soy group were 6.0 and 0.0 (P < .001); day 4, 24.0 and 3.0 (P < .001); and day 8, 0.0 and 3.0 (P < .001), respectively.


CONCLUSIONS
Although there appears to be a trend toward biochemical protection and a marked reduction of necrosis and inflammation, there was no significant liver function test difference between control and Menhaden groups. Considering our data of blunted histologic hepatotoxicity with omega-3 fatty acid supplementation, we hypothesize that this may be a method of reducing long-term complications of liver injury secondary to diseases of cholestasis such as biliary atresia, namely fibrosis and cirrhosis.
Lee
Sang
S
Department of Surgery, The Vascular Biology Program, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA.
Kim
Sendia
S
Le
Hau D
HD
Meisel
Jonathan
J
Strijbosch
Robbert A M
RA
Nose
Vania
V
Puder
Mark
M
D000821:Animal Feed; D000818:Animals; D017209:Apoptosis; D001656:Biliary Atresia; D001651:Cholestasis, Extrahepatic / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003135:Common Bile Duct; D004195:Disease Models, Animal; D004341:Drug Evaluation; D053222:Fas Ligand Protein / Q000502:physiology; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000627:therapeutic use*; D005395:Fish Oils / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D005527:Food, Fortified; D006505:Hepatitis / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D022781:Hepatocytes / Q000473:pathology*; D008026:Ligation; D008103:Liver Cirrhosis / Q000209:etiology / Q000517:prevention & control; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009336:Necrosis; D013024:Soybean Oil / Q000008:administration & dosage / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D008563:Membrane Lipids; D014409:Tumor Necrosis Factor-alpha; C033266:Menhaden oil; D013024:Soybean Oil