Use of sildenafil and L-arginine in an experimental rat model for the prevention of neonatal necrotizing enterocolitis

Sci Rep. 2022 Apr 13;12(1):6206. doi: 10.1038/s41598-022-10323-8.

Abstract

Necrotizing enterocolitis (NEC) has a 45% mortality in neonatal intensive care units. This paper aimed to evaluate the isolated and combined effects of sildenafil and L-arginine in the prevention of necrotizing enterocolitis. Neonatal rats were fed formula milk and submitted to hypoxia under a 100% N2 atmosphere for 70 s. Then, animals were subjected to hypothermia (4 °C for 10 min), twice a day for 3 days. Forty neonatal rats were divided into five groups: negative control-not submitted to the protocol (n = 5), sildenafil group-NEC protocol (n = 9), L-arginine group-NEC protocol (n = 9), L-arginine and sildenafil group-NEC protocol (n = 9) and positive control-NEC protocol and intraperitoneal saline solution (n = 8). Jejunum and terminal ileus were removed for histopathologic and immunohistochemical Ki-67 analysis. Kruskal-Wallis test was used to analyze mortality, survival, body weight, intestinal injury score and Ki-67 proliferation index. All animals submitted to the protocol developed enterocolitis. Mortality rate was higher in group that received only L-arginine (p = 0.0293). The Ki-67 analysis showed a higher proliferative index in groups that received interventional drugs (p = 0.017). In conclusion, sildenafil and L-arginine were not effective to reduce intestinal injury.

MeSH terms

  • Animals
  • Animals, Newborn
  • Arginine / therapeutic use
  • Disease Models, Animal
  • Enterocolitis, Necrotizing* / drug therapy
  • Enterocolitis, Necrotizing* / pathology
  • Enterocolitis, Necrotizing* / prevention & control
  • Humans
  • Infant, Newborn
  • Infant, Newborn, Diseases* / drug therapy
  • Ki-67 Antigen
  • Rats
  • Sildenafil Citrate / pharmacology
  • Sildenafil Citrate / therapeutic use

Substances

  • Ki-67 Antigen
  • Arginine
  • Sildenafil Citrate