PPAR-γ activator induces neuroprotection in hypercholesterolemic rats subjected to global cerebral ischemia/reperfusion injury: in vivo and in vitro inhibition of oxidative stress
| Autor: | Fawzia Al Rouq, Eman El Eter |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Agonist
Male Aging medicine.medical_specialty medicine.drug_class Hypercholesterolemia Ischemia Brain Edema medicine.disease_cause Biochemistry Neuroprotection Proinflammatory cytokine Brain Ischemia Brain ischemia Rosiglitazone Endocrinology Internal medicine Genetics Medicine Animals Rats Wistar Molecular Biology Peroxidase Dose-Response Relationship Drug business.industry Interleukin-6 Tumor Necrosis Factor-alpha Cell Biology medicine.disease Glutathione Rats PPAR gamma Oxidative Stress Neuroprotective Agents Reperfusion Injury Thiazolidinediones Lipid Peroxidation business Reperfusion injury Oxidative stress medicine.drug |
| Zdroj: | Experimental gerontology. 51 |
| ISSN: | 1873-6815 |
| Popis: | Hypercholesterolemia (HC) and aging combine to increase the incidence of cerebrovascular disease through oxidative stress. Our investigation examined the effects of diet-induced hypercholesterolemia (2% for 8weeks) on the extent of brain injury in response to global cerebral ischemia/reperfusion (GCI/R) and the neuroprotective potentials of rosiglitazone in relation to oxidative stress. HC exacerbated the decline in the brain levels of GSH and the increase in MPO, proinflammatory markers and hippocampal lesions in response to GCI/R. HC rats receiving rosiglitazone, PPAR-γ agonist, demonstrated preservation of cell viability of CA1 hippocampal region and attenuation of brain edema. They also showed elevated levels of GSH and low levels of the other parameters similar to non-HC rats subjected to GCI/R. In vitro, rosiglitazone dose-dependently inhibited ROS generation by neutrophils. The results suggest exacerbation of brain lesions by HC in response to GCI/R. The neuroprotective therapeutic potentials of rosiglitazone are comparable to non-HC animals. Mechanisms of protection are possibly due to anti-oxidant, anti-inflammatory effects and scavenging properties of rosiglitazone. These results add to the beneficial therapeutic effects of rosiglitazone and its significance for age-associated diseases including hypercholesterolemia. |
| Databáze: | OpenAIRE |
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