• M H LeBlanc, Y Feng, and J D Fratkin.
• Department of Pediatrics, University of Mississippi Medical Center, 2500 North State Street, Jackson, MI 39216-4505, USA. mleblanc@ped.umsmed.edu
• Eur. J. Pharmacol. 2000 Mar 3; 390 (3): 249-56.

AbstractN-tosyl-L-phenylalanyl-chloromethylketone (TPCK) in vitro blocks apoptotic pathways leading to cell death. We wished to see if TPCK would reduce brain injury in vivo. Seven-day-old rat pups had the right carotid artery ligated and then received either vehicle or TPCK (5 to 100 mg/kg i.p.). They were then given 8% oxygen for 2.25 h. Twenty-two days later, the cerebral hemispheres were weighed to determine the reduction in size in the right hemisphere. TPCK decreased the reduction in right hemisphere weight from 15+/-3% (vehicle, n=20), to 4+/-2% (10 mg/kg, n = 19, P<0.01). TPCK reduced the number of cells staining for DNA breaks 3 days after injury from 1729+/-275 mm(-2) (vehicle, n = 8) to 550+/-236 mm(-2) (10 mg/kg TPCK, n = 9, P<0.01), decreased the amount of DNA fragmentation 3 days after injury by gel electrophoreses (20 mg/kg, n = 16, P<0.01) and eliminated the increase in nitric oxide metabolites 6 h after injury (vehicle 1.5+/-0.4, n = 10; and 20 mg/kg TPCK 0.0+/-0.1 nM/mg protein, n = 10, P<0.001). TPCK pretreatment in the newborn rat model of hypoxic-ischemic brain injury reduces DNA fragmentation, nitric oxide production and brain injury.

30 keywords...

hide…