title: Peroxisome proliferator-activated receptor-γ agonist pioglitazone reduces the development of necrotizing enterocolitis in a neonatal preterm rat model.
abstract: Factors affecting innate immunity and acting as inflammatory regulators, such as the nuclear peroxisome proliferator-activated receptors (PPAR) could be crucial in the pathogenesis of necrotizing enterocolitis (NEC). We hypothesized that the PPARγ agonist pioglitazone (PIO) might be effective in preventing the development of NEC and/or reducing its severity.
  
  
  
  We studied preterm rats in which NEC was induced using the hypoxia-hypothermia model. The treatment group (TG; n = 30) received enteral PIO (10 mg/kg/d) for 72 h and the control group (CG; n = 30) did not. Animals were sacrificed 96 h after birth. NEC was diagnosed evaluating histological ileum changes, and mRNA levels of IL-4, IL-12, IL-6, IL-10, INF-γ, and TNF-α cytokines were measured.
  
  
  
  NEC occurrence was higher in the CG (18/30; 60%) than in the TG (5/30; 16.7%) and was more severe. Proinflammatory IL-12 and INF-γ mRNA levels were significantly lower in the TG than in the CG; conversely, the anti-inflammatory IL-4 mRNA level was significantly higher in the TG than in the CG.
  
  
  
  Our results demonstrate for the first time that PIO is effective in reducing the incidence and severity of NEC and in decreasing renal injuries in a preterm rat model.
authors.affiliation: Division of Neonatology, Careggi University Hospital of Florence, Florence, Italy.
authors.forename: Iuri
authors.initials: I
authors.lastname: Corsini
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Polvani
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.
authors.forename: Mirko
authors.initials: M
authors.lastname: Tarocchi
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Tempesti
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.
authors.forename: Giada
authors.initials: G
authors.lastname: Marroncini
authors.affiliation: Division of Neonatology, Careggi University Hospital of Florence, Florence, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Generoso
authors.affiliation: Division of Neonatology, Careggi University Hospital of Florence, Florence, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Bresci
authors.affiliation: Division of Neonatology, Careggi University Hospital of Florence, Florence, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Gozzini
authors.affiliation: Division of Neonatology, Careggi University Hospital of Florence, Florence, Italy.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Bianconi
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Galli
authors.affiliation: Department of Neurosciences, Psychology, Drug Research and Child Health, Careggi University Hospital of Florence, Florence, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Dani
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D020345:Enterocolitis, Necrotizing / Q000235:genetics* / Q000517:prevention & control*; D005355:Fibrosis; D007035:Hypothermia; D000860:Hypoxia; D007113:Immunity, Innate; D007249:Inflammation; D007668:Kidney / Q000473:pathology; D047495:PPAR gamma / Q000819:agonists*; D000077205:Pioglitazone; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D045162:Thiazolidinediones / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D047495:PPAR gamma; D012333:RNA, Messenger; D045162:Thiazolidinediones; D000077205:Pioglitazone