ABSTRACT
BACKGROUND: Intestinal permeability is thought to be of major relevance for digestive and nutrition-related diseases, and therefore has been studied in numerous mouse models of disease. However, it is unclear which tools are the preferable ones, and how normal values should be defined. AIMS: To compare different in vivo permeability tests in healthy mice of commonly used genetic backgrounds. METHODS: We assessed the intestinal barrier in male and female C57BL/6J and BALB/cJ mice of different ages, using four orally administered permeability markers, FITC-dextran 4000 (FITC-D4000) and ovalbumin (OVA) measured in plasma, and polyethylene glycol (PEG) and lactulose/mannitol (Lac/Man) measured in urine, and by assessing lipopolysaccharide (LPS) in portal vein plasma. RESULTS: After gavage, FITC-D4000, OVA, Lac/Man, and PEG400, but not PEG4000, were detectable in plasma or urine. Female mice tended to have a higher permeability according to the FITC-D4000, OVA, and PEG400 tests, but the Lac/Man ratio was higher in males. No significant differences between the two mouse strains of young and old mice were observed except for mannitol recovery, which was higher in BALB/cJ mice compared to C57BL/6J mice (p < 0.05). Virtually no LPS was detected in healthy mice. For all markers, normal values have been defined based on 5th-95th percentile ranges of our data. CONCLUSION: Selected oral permeability tests, such as FITC-D4000, OVA, PEG400, and Lac/Man, as well as LPS measurements in portal vein plasma, could be suitable for the evaluation of the intestinal barrier in mice, if used in a standardized way.
Subject(s)
Dextrans/metabolism , Fluorescein-5-isothiocyanate/analogs & derivatives , Intestinal Mucosa/metabolism , Lactulose/metabolism , Lipopolysaccharides/metabolism , Mannitol/metabolism , Ovalbumin/metabolism , Permeability , Polyethylene Glycols/metabolism , Animals , Dextrans/blood , Female , Fluorescein-5-isothiocyanate/metabolism , Lactulose/urine , Lipopolysaccharides/blood , Male , Mannitol/urine , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Ovalbumin/blood , Portal VeinABSTRACT
To investigate the hypothesis that an oral supplementation of Bifidobacterium adolescentis protects against a diet-induced nonalcoholic steatohepatitis in a mouse model, C57BL/6 mice were fed either a Western-style or a control diet±tap water fortified with B. adolescentis (5×10(7) cfu/ml) ad libitum for 12 weeks. Mice fed a Western-style diet gained significantly more weight than mice fed a control diet and developed a mild steatohepatitis. Western-style diet fed groups concomitantly treated with B. adolescentis had significantly decreased liver damage, whereas portal endotoxin levels and toll-like receptor-4 protein levels as well as myeloid differentiation factor 88 mRNA were increased in livers of both Western-style diet fed groups. The protective effects of the B. adolescentis were associated with a significant attenuation of the formation of reactive oxygen species, activation of nuclear factor κB (NFκB) and induction of markers of inflammation in the liver. Taken together, our data suggest that an oral supplementation of the B. adolescentis attenuates diet-induced steatohepatitis, and this effect is associated with prevention from lipid peroxidation, NFκB activation and finally inflammation in the liver.
Subject(s)
Bifidobacterium/physiology , Disease Models, Animal , Fatty Liver/prevention & control , Animals , Base Sequence , DNA Primers , Lipid Peroxidation , Mice , Mice, Inbred C57BLABSTRACT
In the last three decades the prevalence of non-alcoholic fatty liver disease has markedly increased. Results from epidemiologic studies indicate that not only a general overnutrition but rather a diet rich in sugar, fat and cholesterol (= Western style diet) maybe a risk factor for the development of non-alcoholic fatty liver disease. Concerning liver diseases, it is known that Deleted in malignant brain tumors 1 is amongst others related to liver injury and repair. In addition Deleted in malignant brain tumors 1 seems to play a role in regard to the maintenance of the intestinal homeostasis and the regulation of food intake. Starting from this background the aim of the present study was to investigate if Dmbt1 plays a role in Western style diet-induced non-alcoholic steatohepatitis in mice. Dmbt1 (+/+) and Dmbt1 (-/-) mice were fed a Western style diet or control diet ad libitum for 12 weeks. Both Western style diet fed groups gained significant more weight than the controls and developed a mild non-alcoholic steatohepatitis. The presence/absence of functional Deleted in malignant brain tumors 1 had no effect on parameters like food intake, weight gain, fasting glucose, and liver damage. These results suggest that Deleted in malignant brain tumors 1 plays a minor part on the development of a diet-induced liver damage in mice.
