The Effects of Intraperitoneal Pentoxifylline Treatment in Rat Pups With Hypoxic-Ischemic Encephalopathy

• Published in: Pediatric neurology Vol. 49; no. 5; pp. 319 - 323
• Main Authors: Kalay, Salih, MD, Oztekin, Osman, MD, Tezel, Gonul, MD, Aldemir, Hakan, MD, Sahin, Emel, PhD, Koksoy, Sadi, MD, Akcakus, Mustafa, MD, Oygur, Nihal, MD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2013
• Subjects: Animals; Animals, Newborn; Brain - drug effects; Brain - metabolism; Caspase 3 - genetics; Caspase 3 - metabolism; caspase-3; cytokine; Disease Models, Animal; Female; Gene Expression Regulation - drug effects; Hypoxia-Ischemia, Brain - complications; Hypoxia-Ischemia, Brain - drug therapy; Hypoxia-Ischemia, Brain - pathology; hypoxic ischemic encephalopathy; Injections, Intraperitoneal; Interleukin-1beta - genetics; Interleukin-1beta - metabolism; Male; Neurology; Pediatrics; pentoxifylline; Pentoxifylline - administration & dosage; Platelet Aggregation Inhibitors - therapeutic use; Rats; Rats, Wistar; RNA, Messenger - metabolism; Statistics, Nonparametric; Time Factors; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - metabolism; cytokine; pentoxifylline; hypoxic ischemic encephalopathy; caspase-3
• ISSN: 0887-8994; 1873-5150
• DOI: 10.1016/j.pediatrneurol.2013.05.011

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.