Effects of Enterally Administered Surfactant in a Rat Model of Necrotizing Enterocolitis

Abstract

Background: Despite technical and scientific improvements in neonatal medicine, there is still no efficient treatment for or prevention of neonatal necrotizing enterocolitis (NEC). Objective: The aim of this study was to determine the protective effect of surfactant on intestinal cells in hypoxia-induced experimental NEC in rats. Methods: The study was performed on Sprague Dawley rat pups divided into three groups. Group 1 served as nonhypoxic controls (n = 15). Group 2 rats (untreated; n = 15) were subjected to hypoxia and reoxygenation (H/O). Group 3 rats (surfactant treated; n = 15) were treated with surfactant (Curosurf; 400 mg/kg enterally) for 5 days and then subjected to H/O. All animals were killed on day 5, and histological and biochemical examinations were performed on intestinal samples. Results: There were no histopathological changes in the control group. The histological findings in untreated rats were similar to those seen in neonatal NEC, with destruction of villi and crypts and extension to the muscularis layer. The mean histological grade of group 1 was 0.2 (range 0–1), and in group 2, it was 2.1 (range 1–3). There was no statistical difference between the histological grades of groups 2 and 3 (p > 0.05). However, there was a difference between the groups that did and did not receive surfactant with regard to superoxide dismutase (SOD), glutathione peroxidase (GSH) and malondialdehyde (MDA). Conclusion: Although surfactant did not have a protective effect on histological changes in hypoxic neonatal rat intestine, it improves biochemical markers such as SOD and GSH and reduces MDA levels.

Clinical Importance of a Fixed Bowel Loop in the Treatment of Necrotizing Enterocolitis

“…The pathogenesis of NEC is still incompletely understood. Despite all research into possible pathogenic mechanisms and clear advances in neonatal care, NEC-associated morbidity and mortality (up to 50%) have not decreased substantially over the last decades [2,3,4,5,6,7,8,9,10]. …”

Extrapulmonary Surfactant Therapy: Review of Available Data and Research/Development Issues

“…Basically the oral surfactant administration tipped the balance between pro‐ and antioxidant gut capacity. Theoretically, surfactant could be useful for repairing epithelial lesions, as seen in skin 11 and other tissues (see below), but this has not been demonstrated, as surfactant treatment did not result in any histological change in this experimental NEC model 25 . Although these results are interesting, we should remember that NEC is a complex and multifactorial disorder whose pathobiology also involves other pathways and factors.…”

“…Theoretically, surfactant could be useful for repairing epithelial lesions, as seen in skin 11 and other tissues (see below), but this has not been demonstrated, as surfactant treatment did not result in any histological change in this experimental NEC model. 25 Although these results are interesting, we should remember that NEC is a complex and multifactorial Data have been obtained from manufacturers or from the relevant literature. Only "pulmonary-like surfactant" (ie, surfactants that have been used for the classical respiratory indications) and chemical surfactants (ie, compounds that have already been investigated for extrapulmonary uses because of their biophysical characteristics) resulting promising, at least in preclinical studies, have been considered.…”

“…23,24 Based on these concepts, enterally administered poractant alfa has been investigated in a preclinical rat model of hypoxia-induced NEC, and surfactant was able to improve the levels of some markers of oxidative gut injury: notably surfactant increased superoxide dismutase and glutathione peroxidase, whereas it decreased malondialdehyde. 25 Some authors questioned if similar or better results might be produced with the oral administration of superoxide dismutase, maybe in lysosomal preparations, as this strategy would be less expensive. 26 Basically the oral surfactant administration tipped the balance between pro-and antioxidant gut capacity.…”

Porcine versus bovine surfactant therapy for RDS in preterm neonates: pragmatic meta-analysis and review of physiopathological plausibility of the effects on extra-pulmonary outcomes

“…These results are only partially similar to those of the earlier Cochrane meta-analysis [8] but they are also stronger. In fact, compared to the previous work we: 1) included five more trials (accounting for ≈600 neonates); 2) used a trials aggregation based on the current best knowledge, that is, on the clinical equivalence of bovine surfactant [8]; 3) analyzed the effect of possible confounders, such as [46][47][48][49] ↓ Prostaglandins synthesis [50,51] ↓ PVR [46,47,[52][53][54] IVH ↓ PaCO2 and CBF [55][56][57] ↓ PDA [53,54] Better peripheral perfusion [34,42] Improved cerebral oxygenation [58] ROP ↓ oxygen and ROS exposure [49,[59][60][61][62][63] NEC ↓ oxygen and ROS exposure [49,64] Better peripheral perfusion [34,42] Earlier progression to full enteral feeding [65][66][67][68] More details in the text. Abbreviations: ROS Reactive oxygen species, PVR Pulmonary vascular resistances, CBF Cerebral blood flow, PaCO2 Arterial partial pressure of CO2, PDA Patent ductus arteriosus, IVH Intraventricular hemorrhage, ROP Retinopathy of prematurity, NEC Necrotizing enterocolitis antenatal steroids or gestational age, and finally, 4) reviewed the possible physiopathological mechanisms linking surfactant replacement and extra-pulmonary outcomes.…”