Purpose: In vitro supplementation of the bile salt, taurodeoxycholic acid (TDCA), has been shown to stimulate proliferation and prevent intestinal apoptosis in IEC-6 cells. We hypothesize that addition of TDCA to a rodent liquid diet will be protective against induced intestinal injury.
Methods: C57Bl6 mice were fed a liquid diet with or without 50-mg/(kg d) TDCA supplementation. After 6 days, the mice were injected with lipopolysaccharide (LPS) (10 mg/kg) to induce intestinal injury. Specimens were obtained 24 hours later and evaluated for intestinal apoptosis, crypt proliferation, and villus length. A separate cohort of animals was injected with LPS (25 mg/kg) and followed 7 days for survival.
Results: Mice whose diet was supplemented with TDCA had significantly increased survival. After LPS-induced injury, mice supplemented with TDCA showed decreased intestinal apoptosis by both H&E and caspase-3. They also had increased intestinal proliferation by 5-bromo-2'deoxyuridine staining and increased villus length.
Conclusions: Dietary TDCA supplementation alleviates mucosal damage and improves survival after LPS-induced intestinal injury. Taurodeoxycholic acid is protective of the intestinal mucosa by increasing resistance to injury-induced apoptosis, stimulating enterocyte proliferation, and increasing villus length. Taurodeoxycholic acid supplementation also results in an increased survival benefit. Therefore, bile acid supplementation may potentially protect the intestine from injury or infection.
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http://dx.doi.org/10.1016/j.jpedsurg.2010.02.094 | DOI Listing |
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State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environment Sciences, Chinese Academy of Sciences, Beijing 100085, China.
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Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Static cold storage of donor livers at 4 °C incompletely arrests metabolism, ultimately leading to decreases in ATP levels, oxidative stress, cell death, and organ failure. Hydrogen Sulfide (HS) is an endogenously produced gas, previously demonstrated to reduce oxidative stress, reduce ATP depletion, and protect from ischemia and reperfusion injury. HS is difficult to administer due to its rapid release curve, resulting in cellular death at high concentrations.
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