Effects of pentoxifylline on intestinal bacterial overgrowth, bacterial translocation and spontaneous bacterial peritonitis in cirrhotic rats with ascites

Background: Prophylaxis of spontaneous bacterial peritonitis with norfloxacin has been associated to development of antibiotic resistance. We investigated whether pentoxifylline compared to norfloxacin reduces bacterial translocation and spontaneous bacterial peritonitis in rats with CCl4-induced cirrhosis and ascites. Method: After development of cirrhosis and ascites, animals were randomly allocated to receive pentoxifylline (16 mg/kg/d every 8h, oral route, n = 13) or placebo (n =12) for 15 days. An additional group of 8 cirrhotic rats was given norfloxacin (5 mg/kg/d for 15 days). Six healthy rats served as controls. Cecal flora and the prevalence of bacterial translocation and spontaneous bacterial peritonitis were analysed. Serum and ascitic fluid levels of TNF-alpha and cecal levels of malondialdehyde were also measured. Results: Pentoxifylline in comparison to placebo reduced intestinal bacterial overgrowth (21% vs. 67%, p = 0.04), bacterial translocation to cecal lymph nodes (23% vs. 75%, p = 0.03) and prevented spontaneous bacterial peritonitis (0% vs. 33%, p = 0.04) by Enterobacteriaceae. Norfloxacin administration induced similar results. Pentoxifylline (0.18 +/- 0.10 nmol/mg), but not norfloxacin (0.25 +/- 0.13; p = 0.02), significantly reduced cecal mucosal levels of malondialdehyde compared to placebo (0.33 +/- 0.16; p = 0.03). Conclusion: In cirrhotic rats with ascites: (a) pentoxifylline as well as norfloxacin reduced intestinal bacterial overgrowth and bacterial translocation and prevented spontaneous bacterial peritonitis; (b) pentoxifylline, but not norfloxacin, reduced oxidative stress in cecal mucosal. (C) 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.