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Neuroprotective effect of MnTMPyP, a superoxide dismutase/catalase mimetic in global cerebral ischemia is mediated through reduction of oxidative stress and DNA fragmentation.
Eur J Pharmacol. 2007 Apr 30; 561(1-3):72-9.EJ

Abstract

Excessive generation of free radicals and decreased levels of the antioxidant enzymes such as superoxide dismutase (SOD) and catalase have been observed after brain ischemic reperfusion injury. In the present study, we have investigated the neuroprotective potential of MnTMPyP (Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin pentachloride), a SOD/Catalase mimetic in bilateral carotid artery occlusion model of global cerebral ischemia in Mongolian gerbils. Five minutes of bilateral carotid artery occlusion produced global cerebral ischemia, which was evident from the neurological deficits, spontaneous motor activity and the decrease in the number of viable hippocampal CA1 neurons. Global ischemia was also associated with increased levels of malondialdehyde, decreased levels of SOD and catalase, and increased TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) positive cells, indicating oxidative stress and DNA fragmentation. Administration of a single dose of MnTMPyP, 1 mg/kg i.p. (30 min before occlusion), produced no significant neuroprotection; however, 3 mg/kg i.p. (30 min before to occlusion) produced significant reduction in neurological score, spontaneous motor activity and CA1 pyramidal neuronal damage. MnTMPyP also attenuated the increased levels of malondialdehyde and improved the levels of SOD and catalase, and inhibited DNA fragmentation in the ischemic animals. Multiple administration of MnTMPyP, 3 mg/kg i.p. (three times: 30 min before, 1 h and 3 h after occlusion), produced better neuroprotection as compared to single dose administration. This study demonstrates that the neuroprotective effect of MnTMPyP in global ischemia is mediated through reduction in oxidative stress and DNA fragmentation.

Authors+Show Affiliations

Molecular Neuropharmacology Laboratory, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Sector-67, S.A.S. Nagar (Mohali), Punjab-160062, India. sssharma@niper.ac.inNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17320858

Citation

Sharma, Shyam S., and Sangeetha Gupta. "Neuroprotective Effect of MnTMPyP, a Superoxide Dismutase/catalase Mimetic in Global Cerebral Ischemia Is Mediated Through Reduction of Oxidative Stress and DNA Fragmentation." European Journal of Pharmacology, vol. 561, no. 1-3, 2007, pp. 72-9.
Sharma SS, Gupta S. Neuroprotective effect of MnTMPyP, a superoxide dismutase/catalase mimetic in global cerebral ischemia is mediated through reduction of oxidative stress and DNA fragmentation. Eur J Pharmacol. 2007;561(1-3):72-9.
Sharma, S. S., & Gupta, S. (2007). Neuroprotective effect of MnTMPyP, a superoxide dismutase/catalase mimetic in global cerebral ischemia is mediated through reduction of oxidative stress and DNA fragmentation. European Journal of Pharmacology, 561(1-3), 72-9.
Sharma SS, Gupta S. Neuroprotective Effect of MnTMPyP, a Superoxide Dismutase/catalase Mimetic in Global Cerebral Ischemia Is Mediated Through Reduction of Oxidative Stress and DNA Fragmentation. Eur J Pharmacol. 2007 Apr 30;561(1-3):72-9. PubMed PMID: 17320858.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neuroprotective effect of MnTMPyP, a superoxide dismutase/catalase mimetic in global cerebral ischemia is mediated through reduction of oxidative stress and DNA fragmentation. AU - Sharma,Shyam S, AU - Gupta,Sangeetha, Y1 - 2007/01/27/ PY - 2006/04/19/received PY - 2006/12/18/revised PY - 2006/12/21/accepted PY - 2007/2/27/pubmed PY - 2007/5/23/medline PY - 2007/2/27/entrez SP - 72 EP - 9 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 561 IS - 1-3 N2 - Excessive generation of free radicals and decreased levels of the antioxidant enzymes such as superoxide dismutase (SOD) and catalase have been observed after brain ischemic reperfusion injury. In the present study, we have investigated the neuroprotective potential of MnTMPyP (Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin pentachloride), a SOD/Catalase mimetic in bilateral carotid artery occlusion model of global cerebral ischemia in Mongolian gerbils. Five minutes of bilateral carotid artery occlusion produced global cerebral ischemia, which was evident from the neurological deficits, spontaneous motor activity and the decrease in the number of viable hippocampal CA1 neurons. Global ischemia was also associated with increased levels of malondialdehyde, decreased levels of SOD and catalase, and increased TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) positive cells, indicating oxidative stress and DNA fragmentation. Administration of a single dose of MnTMPyP, 1 mg/kg i.p. (30 min before occlusion), produced no significant neuroprotection; however, 3 mg/kg i.p. (30 min before to occlusion) produced significant reduction in neurological score, spontaneous motor activity and CA1 pyramidal neuronal damage. MnTMPyP also attenuated the increased levels of malondialdehyde and improved the levels of SOD and catalase, and inhibited DNA fragmentation in the ischemic animals. Multiple administration of MnTMPyP, 3 mg/kg i.p. (three times: 30 min before, 1 h and 3 h after occlusion), produced better neuroprotection as compared to single dose administration. This study demonstrates that the neuroprotective effect of MnTMPyP in global ischemia is mediated through reduction in oxidative stress and DNA fragmentation. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/17320858/Neuroprotective_effect_of_MnTMPyP_a_superoxide_dismutase/catalase_mimetic_in_global_cerebral_ischemia_is_mediated_through_reduction_of_oxidative_stress_and_DNA_fragmentation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(07)00058-1 DB - PRIME DP - Unbound Medicine ER -