Detail of "5154-02-9"

Reference

Neuroprotective effect of peroxynitrite decomposition catalyst and poly(adenosine diphosphate-ribose) polymerase inhibitor alone and in combination in rats with local cerebral ischemia

Neuroprotective effect of peroxynitrite decomposition catalyst and poly(adenosine diphosphate-ribose) polymerase inhibitor alone and in combination in rats with local cerebral ischemia. Sharma, Shyam S.; Munusamy, Shankar; Thiyagarajan, Meenakshisundaram; Kaul, Chaman L. (Molecular Neuropharmacology Laboratory, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Punjab, India).In this study， 5154-02-9 and 119759-45-4 are also used. Journal of Neurosurgery, 101(4), 669-675 (English) 2004 American Association of Neurological Surgeons. CODEN: JONSAC. ISSN: 0022-3085. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Object: The authors evaluated the neuroprotective effect of 5,10,15,20-tetrakis(N-methyl-4'-pyridyl)porphyrinato-iron(III) (FeTMPyP), a peroxynitrite decompn. catalyst, and 1,5-isoquinolinediol (ISO), a poly(ADP [ADP]-ribose) polymerase (PARP) inhibitor, alone and in combination in rats with focal cerebral ischemia induced by middle cerebral artery occlusion (MCAO). Methods: Male Sprague-Dawley rats were subjected to 2 h of MCAO followed by 22 h of reperfusion. Cerebral infarction and neurol. deficits were estd. after ischemia. I.p. injections of FeTMPyP (1 and 2 mg/kg) and ISO (0.05 and 0.1 mg/kg) were administered alone or in combination in ischemic animals. The PARP activity in vehicle- and drug-treated groups was estd. using anti-poly(ADP-ribose) antibody in immunofluorescence and immunoblotting studies. Two hours of MCAO and 22 h of reperfusion produced significant cerebral infarction and neurol. deficits. Treatment with FeTMPyP (1 and 2 mg/kg) and ISO (0.05 and 0.1 mg/kg) produced a significant redn. in cerebral infarction and neurol. deficits. Combination therapy (2 mg/kg FeTMPyP and 0.1 mg/kg ISO) enhanced the inhibition of ischemic vol. (77.81 ± 0.86%) compared with monotherapies (FeTMPyP 54.07 ± 5.6% and ISO 53.06 ± 3.88%). Immunoblotting and immunofluorescence studies showed PARP activation after ischemia, which was reduced by drug treatment. Conclusions: Neuroprotection obsd. with FeTMPyP and ISO alone and in combination may be attributed to inhibition of the peroxynitrite-PARP cascade of cerebral ischemia/reperfusion injury. .