Abstract
Necrotizing enterocolitis (NEC) is a potentially fatal illness in premature neonates. Tumor necrosis factor alpha (TNF-α) has been shown to play a central role in the inflammatory cascade leading to the development of NEC. Published evidence points to a significant role of pentoxifylline in inhibition of TNF-α and in reducing mucosal injury and improving healing in ischemia-reperfusion experiments. Our aim was to investigate the effect of pentoxifylline on the incidence of NEC in a neonatal rat model. Newborn Sprague-Dawley rat pups originating from eight separate litters were delivered by cesarean section at 21.5 d and were formula fed from birth by orogastric gavage. The rat pups were randomized to receive either intraperitoneal pentoxifylline (15 mg/kg/dose) or placebo, given every 8 h beginning at 24 h of age, in a blinded fashion. Experimental NEC was induced by exposure to hypoxia for 60 s followed by cold stress at 4°C for 10 min. The animals were euthanized at development of NEC or at 96 h and intestinal tissue was processed and examined for histologic changes of NEC. The incidence of NEC was significantly lower in the pentoxifylline group [pentoxifylline 5/38 versus placebo 15/36; p = 0.008, odds ratio (OR) = 0.21 95% confidence interval (CI) 0.07–0.67]. Among the pups developing NEC, significantly fewer rat pups treated with pentoxifylline had severe (≥3) intestinal injury scores [pentoxifylline 1/5 versus placebo 10/15; p = 0.031, OR 0.06, 95% CI 0.01–0.79]. We conclude that intraperitoneal administration of pentoxifylline significantly reduced the incidence and severity of NEC in our experimental animal model.
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Abbreviations
- NEC:
-
necrotizing enterocolitis
- PAF:
-
platelet activating factor
- PMN:
-
polymorphonuclear
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Acknowledgements
The authors thank Dr. David Pass at the State Animal Resources Center, Western Australia, and Dr. Linda Manning and her staff at the Animal Facility at Royal Perth Hospital for their support and assistance with maintaining the animals. We also thank Brian Rich, Wombaroo Food Products, Adelaide, South Australia, for providing the rat milk substitute formula used in the study.
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This work was funded by a Channel 7 Telethon Research Fellowship and the Women's and Infant's Research Foundation, Perth, WA.
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Travadi, J., Patole, S., Charles, A. et al. Pentoxifylline Reduces the Incidence and Severity of Necrotizing Enterocolitis in a Neonatal Rat Model. Pediatr Res 60, 185–189 (2006). https://doi.org/10.1203/01.pdr.0000228325.24945.ac
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DOI: https://doi.org/10.1203/01.pdr.0000228325.24945.ac
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