Submitted on December 26, 2007
Accepted on September 24, 2008
Probiotics Enhance Pancreatic Glutathione Biosynthesis and Reduce Oxidative Stress in Experimental Acute Pancreatitis
Femke Lutgendorff1, Lena M. Trulsson2, L. Paul van Minnen3, Ger T. Rijkers3, Harro M. Timmerman3, Lennart E. Franzen4, Hein G. Gooszen3, Louis M.A. Akkermans3, Johan D Soderholm2, and Per Anders Sandstrom2*
1 Department of Clinical and Experimental Medicine, University Hospital Linkoping, Sweden; Gastrointestinal Research Unit, University Medical Center Utrecht, Netherlands
2 Department of Clinical and Experimental Medicine, University Hospital Linkoping, Sweden
3 Gastrointestinal Research Unit, University Medical Center Utrecht, Netherlands
4 Department of Pathology and Cytology, Aleris Medilab, Sweden
* To whom correspondence should be addressed. E-mail: persa{at}ibk.liu.se.
Objective: Factors determining severity of acute pancreatitis (AP) are poorly understood. Oxidative stress causes acinar cell injury and contributes to the severity, while 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.
Design: 53 Male Spraque-Dawley rats were randomly allocated into groups: 1) Control, 2) sham procedure, 3) AP, no treatment, 4) AP, probiotics and 5) AP, placebo. AP was induced under general anesthesia by intraductal glycodeoxycholate infusion (15 mM) and intravenous cerulein (5µg/kg/hr, for 6 hours). 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-
B activation.
Results: 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-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 MDA/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 pre-treatment 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 pre-treated animals.
Conclusions: 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.
