title: Protective effect of telmisartan against oxidative damage induced by high glucose in neuronal PC12 cell.
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 37.5 μM. 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.
authors.affiliation: Department of Pharmacology, Razi Institute of Drug Research, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, Research Center of Molecular Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran. Electronic address: hdoulabi@yahoo.com.
authors.forename: Habib
authors.initials: H
authors.lastname: Eslami
authors.affiliation: Department of Pharmacology, Razi Institute of Drug Research, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Ali M
authors.initials: AM
authors.lastname: Sharifi
authors.affiliation: Department of Molecular Medicine, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Hamzeh
authors.initials: H
authors.lastname: Rahimi
authors.affiliation: Department of Anatomy, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Rahati
mesh_terms: D057912:Angiotensin II Type 2 Receptor Blockers / Q000494:pharmacology*; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D016716:PC12 Cells; D047495:PPAR gamma / Q000037:antagonists & inhibitors; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D000077333:Telmisartan
chemical_list: C457499:2-chloro-5-nitrobenzanilide; D057912:Angiotensin II Type 2 Receptor Blockers; D000813:Anilides; D000975:Antioxidants; D001562:Benzimidazoles; D001565:Benzoates; D018696:Neuroprotective Agents; D047495:PPAR gamma; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D009249:NADP; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione; D005947:Glucose; D000077333:Telmisartan
keywords: High glucose; Oxidative stress; PC12 cells; Telmisartan