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Am J Physiol Gastrointest Liver Physiol 295: G1111-G1121, 2008. First published October 2, 2008; doi:10.1152/ajpgi.00603.2007
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INFLAMMATION/IMMUNITY/MEDIATORS

Probiotics enhance pancreatic glutathione biosynthesis and reduce oxidative stress in experimental acute pancreatitis

Femke Lutgendorff,1,2 Lena M. Trulsson,1 L. Paul van Minnen,2 Ger T. Rijkers,2 Harro M. Timmerman,2 Lennart E. Franzén,3 Hein G. Gooszen,2 Louis M. A. Akkermans,2 Johan D. Söderholm,1 and Per A. Sandström1

1Department of Clinical and Experimental Medicine, Division of Surgery, Linköping University and University Hospital Linköping, Linköping; 2Gastrointestinal Research Unit, Department of Surgery, University Medical Center, Utrecht, The Netherlands; and 3Department of Pathology and Cytology, Aleris Medilab, Täby, Sweden

Submitted 26 December 2007 ; accepted in final form 24 September 2008

Factors determining severity of acute pancreatitis (AP) are poorly understood. Oxidative stress causes acinar cell injury and contributes to the severity, whereas prophylactic probiotics ameliorate experimental pancreatitis. Our objective was to study how probiotics affect oxidative stress, inflammation, and acinar cell injury during the early phase of AP. Fifty-three male Sprague-Dawley rats were randomly allocated into groups: 1) control, 2) sham procedure, 3) AP with no treatment, 4) AP with probiotics, and 5) AP with placebo. AP was induced under general anesthesia by intraductal glycodeoxycholate infusion (15 mM) and intravenous cerulein (5 µg·kg–1·h–1, for 6 h). Daily probiotics or placebo were administered intragastrically, starting 5 days prior to AP. After cerulein infusion, pancreas samples were collected for analysis including lipid peroxidation, glutathione, glutamate-cysteine-ligase activity, histological grading of pancreatic injury, and NF-{kappa}B activation. The severity of pancreatic injury correlated to oxidative damage (r = 0.9) and was ameliorated by probiotics (1.5 vs. placebo 5.5; P = 0.014). AP-induced NF-{kappa}B activation was reduced by probiotics (0.20 vs. placebo 0.53 OD450nm/mg nuclear protein; P < 0.001). Probiotics attenuated AP-induced lipid peroxidation (0.25 vs. placebo 0.51 pmol malondialdehyde/mg protein; P < 0.001). Not only was AP-induced glutathione depletion prevented (8.81 vs. placebo 4.1 µmol/mg protein, P < 0.001), probiotic pretreatment even increased glutathione compared with sham rats (8.81 vs. sham 6.18 µmol/mg protein, P < 0.001). Biosynthesis of glutathione (glutamate-cysteine-ligase activity) was enhanced in probiotic-pretreated animals. Probiotics enhanced the biosynthesis of glutathione, which may have reduced activation of inflammation and acinar cell injury and ameliorated experimental AP, via a reduction in oxidative stress.

reactive oxygen species; Lactobacillus; Bifidobacterium; glutamate-cysteine ligase; lipid peroxidation



Address for reprint requests and other correspondence: P. A. Sandström, Dept. of Clinical and Experimental Medicine, Division of Surgery, Univ. Hospital, 581 85 Linköping, Sweden (e-mail: persa{at}ibk.liu.se)







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