Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04179 (MnSOD)
 2,777 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pilocarpine is a cholinergic agonist capable to induce seizures and an epilepticus-like state in rodents. This status epilepticus (SE) is an useful animal model to study the development and understanding of the neuropathology, behavioural and electroencephalographic alterations of human temporal lobe epilepsy. It has been suggested a relationship between SE and reactive oxygen species (ROS) that can result in seizure-induced neurodegeneration. The aim of this study was to evaluate the existence of oxidative damage and the changes in the antioxidant system in cortex after administration of a high pilocarpine dose. Rats were injected with pilocarpine (350 mg/kg i.p.) or with saline as control and 2h after the animals were sacrificed. Malondialdehyde (MDA) levels, as marker of lipid peroxidation, significantly increased (64%) after pilocarpine treatment evidencing oxidative damage. Antioxidant enzyme activities--catalase (CAT), glutathione peroxidase (GP) and superoxide dismutase (SOD)--significantly increased in response to pilocarpine (28%, 28% and 21%, respectively). GP and Mn-SOD gene expression were induced by pilocarpine treatment. Vitamin E concentration in brain cortex decreased (15%) as result of pilocarpine administration. In conclusion, the high dose of pilocarpine, used in the present study, induces oxidative damage and increases antioxidant enzyme activities and expression in brain cortex. Moreover, increased lipid peroxidation produces the consumption of Vitamin E.
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PMID:Antioxidant response and oxidative damage in brain cortex after high dose of pilocarpine. 1720 54

Alpha-tocopherol has numerous nonenzymatic actions and is a powerful liposoluble antioxidant. The objective of the present study was to evaluate the neuroprotective effects of alpha-tocopherol in rats against oxidative stress caused by pilocarpine-induced seizures. Wistar rats were intraperitoneally treated with 0.9% saline (control group), alpha-tocopherol (200 mg/kg, alpha-tocopherol group), pilocarpine (400 mg/kg, pilocarpine group), or the combination of alpha-tocopherol (200 mg/kg) and pilocarpine (400 mg/kg, i.p.; alpha-tocopherol plus pilocarpine group). After the treatments, all groups were observed for 24 h. The superoxide dismutase (Mn-SOD) and catalase activities, lipid peroxidation and nitrite concentrations were measured using spectrophotometrically methods. To clarify the mechanism of alpha-tocopherol on oxidative stress in pilocarpine model, Western blot analysis of Mn-SOD and catalase in rat striatum were performed. In the pilocarpine group, rats showed a significant increase in lipid peroxidation and nitrite levels. However, there were no alterations on Mn-SOD activity. On the other hand, the catalase activity augmented in pilocarpine group. In the alpha-tocopherol and pilocarpine co-administered rats, antioxidant treatment significantly reduced the lipid peroxidation level and nitrite content and increased the Mn-SOD and catalase activities in rat striatum after seizures. Pilocarpine, alpha-tocopherol plus pilocarpine and alpha-tocopherol groups did not affect of the Mn-SOD and catalase mRNA or protein levels. Our findings strongly support the hypothesis that oxidative stress occurs in striatum during pilocarpine-induced seizures, indicating that brain damage induced by the oxidative process plays a crucial role in seizures pathogenic consequences, which implies that strong protective effect could be achieved using alpha-tocopherol.
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PMID:Oxidative stress in rat striatum after pilocarpine-induced seizures is diminished by alpha-tocopherol. 2174 65