title: The effects of intraperitoneal pentoxifylline treatment in rat pups with hypoxic-ischemic encephalopathy.
abstract: BACKGROUND
  The aim of this study was to evaluate the effects of postischemic treatment with pentoxifylline on the cytokine gene expressions and neuronal apoptosis in neonatal rat model of hypoxic-ischemic encephalopathy.
  
  
  METHODS
  Seven-day-old Wistar rat pups (n = 40) of either sex, delivered spontaneously, were used in this experimental study. Control group (n = 8): after median neck incision was made, neither ligation nor hypoxia was performed, ischemia group (n = 16): 0.5 mL of saline was injected intraperitoneally immediately after hypoxia. Pentoxifylline and ischemia groups (n = 16): the rat pups were administered intraperitoneally 60 mg/kg of pentoxifylline immediately after hypoxia. Eight rats from ischemia and pentoxifylline + ischemia groups were sacrificed 4 and 24 hours after drug administration. Control group mice were decapitated 4 hours after hypoxia. Caspase-3 activity, interleukin-1β, and tumor necrosis factor-α messenger RNA expression levels were studied in the left half of the brain.
  
  
  RESULTS
  Induction of cerebral ischemia increased tumor necrosis factor-α and interleukin-1β messenger RNA expression levels significantly at 4 hours and 24 hours following ischemia in the left ischemic hemispheres in the ischemia group as compared with the control group. Systemic administration of pentoxifylline immediately after hypoxic-ischemic encephalopathy significantly reduced the tumor necrosis factor-α and interleukin-1β messenger RNA expression levels in ischemic tissue as compared with the ischemia group. Caspase-3 activities in the left half of the brains of ischemia group were found to be increased significantly as compared with control group. Caspase-3 activities in the brains of pentoxifylline + ischemia groups were significantly lower than in that of ischemia group.
  
  
  CONCLUSIONS
  Based on the significantly lower interleukin-1β and tumor necrosis factor-α gene expression measured after 4 and 24 hours and significantly reduced caspase-3 activity measured colorimetrically in the animals treated with pentoxifylline, our findings suggest that pentoxifylline may reduce brain damage due to hypoxic-ischemic injury.
authors.affiliation: Division of Neonatology, Department of Pediatrics, School of Medicine, Akdeniz University, Antalya, Turkey.
authors.forename: Salih
authors.initials: S
authors.lastname: Kalay
authors.forename: Osman
authors.initials: O
authors.lastname: Oztekin
authors.forename: Gonul
authors.initials: G
authors.lastname: Tezel
authors.forename: Hakan
authors.initials: H
authors.lastname: Aldemir
authors.forename: Emel
authors.initials: E
authors.lastname: Sahin
authors.forename: Sadi
authors.initials: S
authors.lastname: Koksoy
authors.forename: Mustafa
authors.initials: M
authors.lastname: Akcakus
authors.forename: Nihal
authors.initials: N
authors.lastname: Oygur
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D020925:Hypoxia-Ischemia, Brain / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D007274:Injections, Intraperitoneal; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008297:Male; D010431:Pentoxifylline / Q000008:administration & dosage*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018709:Statistics, Nonparametric; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D010975:Platelet Aggregation Inhibitors; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D053148:Caspase 3; D010431:Pentoxifylline
keywords: caspase-3; cytokine; hypoxic ischemic encephalopathy; pentoxifylline