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Hormozgan University of Medical Sciences

Protective effect of telmisartan against oxidative damage induced byhigh glucose in neuronal PC12 cell

(2014) Protective effect of telmisartan against oxidative damage induced byhigh glucose in neuronal PC12 cell. Neuroscience Letters.

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Abstract

Telmisartan is an angiotensin II type 1 receptor blocker and partial agonist of peroxisome proliferator-activated receptor gamma (PPAR-�). Here, we investigated the protective capacity of telmisartanagainst high glucose (HG)-elicited oxidative damage in PC12 cells. The activity of lactate dehydroge-nase (LDH), NADPH oxidase (NOX), superoxide dismutase (SOD), catalase (CAT) as well as the levelsof malondialdehyde (MDA), glutathione (GSH), intracellular reactive oxygen species (ROS), cell viabil-ity and DNA fragmentation were measured in HG-treated PC12 cells with and without telmisartanco-treatment. Moreover, the direct antioxidant effect of telmisartan was determined by 2,2-azinobis-(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assay and protein expression of Bax, Bcl-2, cleavedcaspase-3 and NOX subunit p47phox by western blotting. Telmisartan exhibited antioxidant activity inthe ABTS assay with the IC50value of 37.5 �M. Pretreatment of PC12 cells with telmisartan, prior to HGexposure, was associated with a marked diminution in cleaved caspase-3 expression, DNA fragmenta-tion, Bax/Bcl-2 ratio, intracellular ROS and MDA levels. Additionally, the cell viability, GSH level, SOD andCAT activity were notably elevated by telmisartan, whereas the activity and the protein expression ofNADPH oxidase subunit p47phox were attenuated. Interestingly, co-treatment with GW9662, a PPAR-�antagonist, partially inhibited the beneficial effects of telmisartan. These findings suggest that telmisartanhas protective effects on HG-induced neurotoxicity in PC12 cells, which may be related to its antioxidantaction and inhibition of NADPH oxidase. Furthermore, the results show that PPAR-� activation is involvedin the neuroprotective effects of telmisartan.

Item Type: Article
Keywords: TelmisartanHigh glucoseOxidative stressPC12 cells
Subjects: pharmacology
Depositing User: مرکز تحقیقات پزشکی مولکولی
URI: http://eprints.hums.ac.ir/id/eprint/951

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