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

Abstract

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 microg.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-kappaB 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-kappaB activation was reduced by probiotics (0.20 vs. placebo 0.53 OD(450nm)/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 micromol/mg protein, P < 0.001), probiotic pretreatment even increased glutathione compared with sham rats (8.81 vs. sham 6.18 miccromol/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.

Effect of Multispecies Probiotic Supplements on Metabolic Profiles, hs-CRP, and Oxidative Stress in Patients with Type 2 Diabetes

“…Such findings have also been reached with the consumption of L. fermentum ME-3 [52] and multispecies probiotics in rats [53]. However, in our previous study in pregnant women [54], consumption of probiotic yogurt containing two strains of L. acidophilus LA5 and B. animalis BB12 did not lead to a significant effect on GSH compared to conventional yogurt.…”

The effect of quercetin on cerulein-induced acute pancreatitis

“…Pancreatic GSH depletion has been shown in the initial phase of acute pancreatitis. 8,11,37,38 However, while some reports have shown increased pancreatic GSSG in AP, 13,14,[37][38][39] others have found that pancreatic GSSG levels and the GSSG/GSH ratio remains essentially unchanged during the early course of AP. 10,12,14,39 Rau et al 12 demonstrated a significant decrease of GSH levels parallel with an increased ratio of GSSG/Total glutathione.…”

Role of Probiotics in Pancreatic Cancer Prevention: The Prospects and Challenges

“…Furthermore, Lutgendorff et al, 2008 reported that probiotics enhanced the biosynthesis of glutathione [132] and reduce inflammation and acinar cell injury and ameliorated experimental pancreatitis, by reduction in oxidative stress. The scientific studies also proved that reduction in pancreatic DNA damage and its associated effects in CP were observed by treatment with probiotics [133] which led to the prevention of pancreatic cancer. Though, more rigorous studies will be required to investigate the potential effects of probiotics as anti-oxidative role that can be the one of the great solution for combating this noxious form of cancer.…”