Abstract | BACKGROUND: AIM: The present study investigated the pharmacological role of tempol in the treatment of rat neonatal cortical mitochondrial dysfunction induced insult progression (day-1 to day-7) and associated neurobehavioral alterations post- anoxia. METHODS: Rat pups of 30h age or postnatal day 2 (PND2) were randomly divided into 5 groups (n=5 per group): (1) Control; (2) Anoxia; (3) Anoxia+Tempol 75mg/kg; (4) Anoxia+Tempol 150mg/kg; and (5) Anoxia+Tempol 300mg/kg, and subjected to two episode of anoxia (10min each) at 24h of time interval in an enclosed chamber supplied with 100% N2. RESULTS:
Tempol significantly decreased nitric oxide (NO) formation and simultaneously improved superoxide dismutase (SOD) and catalase (CAT) activities. Further, we observed a significantly (P<0.05) improvement in mitochondrial respiration, complex enzyme activities, mitochondrial membrane potential ( MMP) along with attenuation of transition pore opening (MPT) after treatment with tempol. Furthermore, tempol decreased expression of mitochondrial Bax, cytochrome-C, caspase-9 and caspase-3 while the increase in expression of cytoplasmic Bax, mitochondrial Bcl-2 on day-7 in cortical region indicating regulation of intrinsic pathway of apoptosis. Further, it improved anoxia-induced neurobehavioral outcome (hanging and reflex latencies). CONCLUSION: Biochemical, molecular and behavioral studies suggest the role of tempol in preserving mitochondrial function and associated neurobehavioral outcomes after neonatal anoxia.
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Authors | Puneet K Samaiya, Gopeshwar Narayan, Ashok Kumar, Sairam Krishnamurthy |
Journal | Journal of the neurological sciences
(J Neurol Sci)
Vol. 375
Pg. 58-67
(Apr 15 2017)
ISSN: 1878-5883 [Electronic] Netherlands |
PMID | 28320189
(Publication Type: Journal Article)
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Copyright | Copyright © 2017 Elsevier B.V. All rights reserved. |
Chemical References |
- Antioxidants
- Cyclic N-Oxides
- Proto-Oncogene Proteins c-bcl-2
- Spin Labels
- Nitric Oxide
- Cytochromes c
- Catalase
- Superoxide Dismutase
- Succinate Dehydrogenase
- NADH Dehydrogenase
- tempol
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Topics |
- Animals
- Animals, Newborn
- Antioxidants
(therapeutic use)
- Apoptosis
(drug effects)
- Catalase
(metabolism)
- Cyclic N-Oxides
(therapeutic use)
- Cytochromes c
(metabolism)
- Disease Models, Animal
- Disease Progression
- Dose-Response Relationship, Drug
- Hypoxia
(complications)
- Membrane Potential, Mitochondrial
(drug effects)
- Mitochondrial Diseases
(drug therapy, etiology)
- Muscle Strength
(drug effects)
- NADH Dehydrogenase
(metabolism)
- Nitric Oxide
(metabolism)
- Proto-Oncogene Proteins c-bcl-2
(metabolism)
- Rats
- Reflex
(drug effects)
- Spin Labels
- Succinate Dehydrogenase
(metabolism)
- Superoxide Dismutase
(metabolism)
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