Pentoxifylline Does Not Prevent Hypoxia/Reoxygenation-Induced Necrotizing Enterocolitis

Erdener, Dilek; Bakirtas, Figen; Alkanat, Murat; Mutaf, Isil; Habif, Sara; Bayındır, Oya

doi:10.1159/000077290

Cited by 15 publications

(6 citation statements)

References 20 publications

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“…Erdener et al (38) did not observe such a protective effect of pentoxifylline on NEC in their hypoxia/reperfusion model using 1-d-old newborn rabbits. This model, however, differs substantially from ours in that it utilized a different species and used hypoxia as the only stress factor.…”

Section: Discussionmentioning

confidence: 84%

Pentoxifylline Reduces the Incidence and Severity of Necrotizing Enterocolitis in a Neonatal Rat Model

et al. 2006

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Necrotizing enterocolitis (NEC) is a potentially fatal illness in premature neonates. Tumor necrosis factor alpha (TNF-␣) 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-␣ and in reducing mucosal injury and improving healing in ischemiareperfusion 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 ϭ 0.008, odds ratio (OR) ϭ 0.21 95% confidence interval (CI) 0.07-0.67]. Among the pups developing NEC, significantly fewer rat pups treated with pentoxifylline had severe (Ն3) intestinal injury scores [pentoxifylline 1/5 versus placebo 10/15; p ϭ 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. (Pediatr Res 60: 185-189, 2006)

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Section: Discussionmentioning

confidence: 84%

Pentoxifylline Reduces the Incidence and Severity of Necrotizing Enterocolitis in a Neonatal Rat Model

et al. 2006

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“…Extrapolating results from animal models to human preterm infants may not be appropriate as the effects of an intervention could be species specific (82)(83)(84)89). For example, intraperitoneal pentoxifylline prevented NEC in a rat model but not in a rabbit model (90,91). Animal models of NEC may not reflect the multifactorial (e.g., intrauterine growth restriction, sepsis, patent ductus arteriosus, indomethacin, no enteral intake, prolonged parenteral nutrition) pathogenesis of classical late-onset NEC in very/extremely preterm infants.…”

Section: Discussionmentioning

confidence: 99%

Effects of probiotics on experimental necrotizing enterocolitis: a systematic review and meta-analysis

2017

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BackgroundMeta-analyses of randomized controlled trials (RCTs) suggest that probiotics decrease the risk of necrotizing enterocolitis (NEC) in preterm infants. Many animal RCTs have evaluated probiotics for preventing NEC. We systematically reviewed the literature on this topic.MethodsThe protocol for systematic review of animal intervention studies (SYRCLE) was followed. Medline, Embase, ISI Web of Science, e-abstracts from the Pediatric Academic Society meetings, and other neonatal conferences were searched in December 2015 and August 2016. RCTs comparing probiotics vs. placebo/no probiotic were included.ResultsA total of 29 RCTs were included (Rats: 16, Mice: 7, Piglets: 3, Quail: 2, Rabbit: 1; N~2,310), with 21 reporting on histopathologically confirmed NEC; remaining 8 assessed only pathways of probiotic benefits. Twenty of the 21 RCTs showed that probiotics significantly reduced NEC. Pooling of data was possible for 16/21 RCTs. Meta-analysis using random-effects model showed that probiotics significantly decreased the risk of NEC (203/641 (31.7%) vs. 344/571 (60.2%); relative risk: 0.51; 95% confidence interval (CI): 0.42-0.62; P<0.00001; I2=44%; number needed to treat: 4; 95% CI: 2.9, 4.3).ConclusionProbiotics significantly reduced NEC via beneficial effects on immunity, inflammation, tissue injury, gut barrier, and intestinal dysbiosis.

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“…However, others have reported no significant improvement with pentoxiphylline in hypoxia/reperfusion-induced rabbit NEC (Ref. 105). …”

Section: Mediators Of Innate Immunitymentioning

confidence: 99%

The immunological landscape in necrotising enterocolitis

Cho

Berger

Nold-Petry

et al. 2016

Expert Rev. Mol. Med.

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Necrotising enterocolitis (NEC) is an uncommon, but devastating intestinal inflammatory disease that predominantly affects preterm infants. NEC is sometimes dubbed the spectre of neonatal intensive care units, as its onset is insidiously non-specific, and once the disease manifests, the damage inflicted on the baby's intestine is already disastrous. Subsequent sepsis and multi-organ failure entail a mortality of up to 65%. Development of effective treatments for NEC has stagnated, largely because of our lack of understanding of NEC pathogenesis. It is clear, however, that NEC is driven by a profoundly dysregulated immune system. NEC is associated with local increases in pro-inflammatory mediators, e.g. Toll-like receptor (TLR) 4, nuclear factor-κB, tumour necrosis factor, platelet-activating factor (PAF), interleukin (IL)-18, interferon-gamma, IL-6, IL-8 and IL-1β. Deficiencies in counter-regulatory mechanisms, including IL-1 receptor antagonist (IL-1Ra), TLR9, PAF-acetylhydrolase, transforming growth factor beta (TGF-β)1&2, IL-10 and regulatory T cells likely facilitate a pro-inflammatory milieu in the NEC-afflicted intestine. There is insufficient evidence to conclude a predominance of an adaptive Th1-, Th2- or Th17-response in the disease. Our understanding of the accompanying regulation of systemic immunity remains poor; however, IL-1Ra, IL-6, IL-8 and TGF-β1 show promise as biomarkers. Here, we chart the emerging immunological landscape that underpins NEC by reviewing the involvement and potential clinical implications of innate and adaptive immune mediators and their regulation in NEC.

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Pentoxifylline Does Not Prevent Hypoxia/Reoxygenation-Induced Necrotizing Enterocolitis

Cited by 15 publications

References 20 publications

Pentoxifylline Reduces the Incidence and Severity of Necrotizing Enterocolitis in a Neonatal Rat Model

Pentoxifylline Reduces the Incidence and Severity of Necrotizing Enterocolitis in a Neonatal Rat Model

Effects of probiotics on experimental necrotizing enterocolitis: a systematic review and meta-analysis

The immunological landscape in necrotising enterocolitis

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