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Repository of Research and Investigative Information

Hormozgan University of Medical Sciences

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

(2014) Protective effect of telmisartan against oxidative damage induced by high 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-γ). Here, we investigated the protective capacity of telmisartan against high glucose (HG)-elicited oxidative damage in PC12 cells. The activity of lactate dehydrogenase (LDH), NADPH oxidase (NOX), superoxide dismutase (SOD), catalase (CAT) as well as the levels of malondialdehyde (MDA), glutathione (GSH), intracellular reactive oxygen species (ROS), cell viability and DNA fragmentation were measured in HG-treated PC12 cells with and without telmisartan co-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, cleaved caspase-3 and NOX subunit p47phox by western blotting. Telmisartan exhibited antioxidant activity in the ABTS assay with the IC50 value of 37.5μM. Pretreatment of PC12 cells with telmisartan, prior to HG exposure, was associated with a marked diminution in cleaved caspase-3 expression, DNA fragmentation, Bax/Bcl-2 ratio, intracellular ROS and MDA levels. Additionally, the cell viability, GSH level, SOD and CAT activity were notably elevated by telmisartan, whereas the activity and the protein expression of NADPH oxidase subunit p47phox were attenuated. Interestingly, co-treatment with GW9662, a PPAR-γ antagonist, partially inhibited the beneficial effects of telmisartan. These findings suggest that telmisartan has protective effects on HG-induced neurotoxicity in PC12 cells, which may be related to its antioxidant action and inhibition of NADPH oxidase. Furthermore, the results show that PPAR-γ activation is involved in the neuroprotective effects of telmisartan. © 2013 Elsevier Ireland Ltd.

Item Type: Article
Additional Information: cited By 17
Keywords: 2 chloro 5 nitrobenzanilide; 2,2' azinobis(3 ethylbenzothiazoline 6 sulfonic acid); caspase 3; catalase; DNA fragment; glucose; glutathione; lactate dehydrogenase; malonaldehyde; protein Bax; protein bcl 2; reactive oxygen metabolite; reduced nicotinamide adenine dinucleotide phosphate oxidase; reduced nicotinamide adenine dinucleotide phosphate oxidase 2; superoxide dismutase; telmisartan, antioxidant activity; article; attenuation; cell viability; controlled study; DNA fragmentation; drug effect; drug inhibition; enzyme activity; glucose intake; human; human cell; IC 50; intracellular membrane; nerve cell; neuroprotection; oxidative stress; PC12 cell; priority journal; protein expression; protein function; scavenging system; Western blotting, High glucose; Oxidative stress; PC12 cells; Telmisartan, Angiotensin II Type 2 Receptor Blockers; Anilides; Animals; Antioxidants; Apoptosis; Benzimidazoles; Benzoates; Catalase; Cell Survival; Glucose; Glutathione; Malondialdehyde; NADP; Neuroprotective Agents; Oxidative Stress; PC12 Cells; PPAR gamma; Rats; Reactive Oxygen Species; Superoxide Dismutase
Subjects: QU Biochemistry. Cell Biology and Genetics > QU 300-560 Cell Biology and Genetics
QV Pharmacology > QV 701-835 Pharmacy and Pharmaceutics
Depositing User: مهندس هدی فهیم پور
URI: http://eprints.hums.ac.ir/id/eprint/4957

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