title: Telmisartan ameliorates oxidative stress and subarachnoid haemorrhage-induced cerebral vasospasm.
abstract: OBJECTIVE
  Growing evidence suggests that oxidative stress is one of the factors contributing to subarachnoid haemorrhage (SAH)-induced cerebral vasospasm. SAH-induced cerebral vasospam alters thioredoxin (Trx) cycle enzymes and thioredoxin-interacting protein (TXNIP) as an important endogenous antioxidant system. In this study, we have explored the effects of telmisartan on the vascular morphological changes, endothelial apoptosis, tissue oxidative stress status and the level of Trx cycle enzymes/ TXNIP in a rabbit SAH model.
  
  
  METHODS
  Forty male New Zealand rabbits were randomly divided into five groups of eight rabbits each: control group, sham group, SAH group, SAH + vehicle group and SAH + telmisartan group. SAH was created by a single cisterna magna blood injection. SAH + telmisartan group received telmisartan treatment (5 mg/kg intraperitoneal, once daily) for 72 h. The brainstem tissue Trx1, Trx2, Trx reductase (TrxR), TrxR1and TXNIP levels were investigated. Total oxidant status (TOS), total antioxidant status (TAS), malondialdehyde (MDA) levels and tumour necrosis factor alpha (TNF alpha) levels were investigated. Basilar artery segments were investigated for cross-sectional area, wall thickness measurements and endothelial apoptosis.
  
  
  RESULTS
  Telmisartan treatment restored the lowered level of Trx1, TrxR, TAS and the expression of TrxR1 seen in SAH. Telmisartan treatment also decreased TXNIP expression, TOS, MDA and TNF alpha levels. Morphological changes of cerebral vasospasm were attenuated after treatment. Endothelial apoptosis significantly reduced.
  
  
  CONCLUSIONS
  Treatment with telmisartan ameliorates oxidative stress and SAH-induced cerebral vasospasm in rabbits. These effects of telmisartan may be associated with downregulation of TXNIP and upregulation of Trx/TrxR.
authors.affiliation: a Necmettin Erbakan University, Meram Faculty of Medicine , Turkey.
authors.forename: Fatih
authors.initials: F
authors.lastname: Erdi
authors.affiliation: a Necmettin Erbakan University, Meram Faculty of Medicine , Turkey.
authors.forename: Fatih
authors.initials: F
authors.lastname: Keskin
authors.affiliation: a Necmettin Erbakan University, Meram Faculty of Medicine , Turkey.
authors.forename: Hasan
authors.initials: H
authors.lastname: Esen
authors.affiliation: b Farabi Hospital , Turkey.
authors.forename: Bulent
authors.initials: B
authors.lastname: Kaya
authors.affiliation: a Necmettin Erbakan University, Meram Faculty of Medicine , Turkey.
authors.forename: Bahadir
authors.initials: B
authors.lastname: Feyzioglu
authors.affiliation: a Necmettin Erbakan University, Meram Faculty of Medicine , Turkey.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Kilinc
authors.affiliation: a Necmettin Erbakan University, Meram Faculty of Medicine , Turkey.
authors.forename: Yasar
authors.initials: Y
authors.lastname: Karatas
authors.affiliation: a Necmettin Erbakan University, Meram Faculty of Medicine , Turkey.
authors.forename: Gokhan
authors.initials: G
authors.lastname: Cuce
authors.affiliation: a Necmettin Erbakan University, Meram Faculty of Medicine , Turkey.
authors.forename: Erdal
authors.initials: E
authors.lastname: Kalkan
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D001565:Benzoates / Q000494:pharmacology / Q000627:therapeutic use*; D001784:Blood Gas Analysis; D001933:Brain Stem / Q000187:drug effects / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins; D004195:Disease Models, Animal; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism; D018709:Statistics, Nonparametric; D013345:Subarachnoid Hemorrhage / Q000150:complications*; D000077333:Telmisartan; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D020301:Vasospasm, Intracranial / Q000188:drug therapy* / Q000209:etiology*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C493796:TXNIP protein, rat; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D013879:Thioredoxins; D000077333:Telmisartan
keywords: Oxidative Stress; Telmisartan; Thioredoxin; Vasospasm