Introduction: Growing evidence suggests that oxidative stress is one of the factors contributing to subarachnoid hemorrhage (SAH) induced cerebral vasospasm. SAH induced cerebral vasospam alters thioredoxin (Trx) cycle enzymes and thioredoxin-interacting protein (TXNIP) as an important endogenous antioxidant sytem. In this study we observe the effects of telmisartan on the vascular morphological changes, endothelial apoptosis, tissue oxidative stress status and the level of Trx cycle enymes/ TXNIP in a rabbit SAH model.
Methods: Forty male New Zealand rabbits were randomly divided into five groups of 8 rabbits each: control group, sham group, SAH group, SAH+vehicle group and SAH+telmisartan group. SAH was created by the single cisterna magna blood injection. SAH+telmisartan group received telmisartan treatment (5mg/kg, once daily, intraperitoneal) for 72 hours.
The brainstem tissue thioredoxin-1(Trx1), thioredoxin-2 (Trx2), thioredoxin reductase (TrxR), thioredoxin reductase-1 (TrxR1) and TXNIP levels were investigated. Total oxidant status (TOS), total antioxidant status (TAS), malondialdehyde levels (MDA) and tumor 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 was statistically significantly increased the level of Trx1, TrxR, TAS and the expression of TrxR1.Telmisartan treatment was 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 ameliorate 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.
Patient Care: Targeting a new potential as thioredoxin system for better understanding SAH induced cerebral vasospasm and offering new drug therapies.
Learning Objectives: Discuss in small groups, the importance of oxidative stress related aspects of cerebral vasospasm and effects of telmisartan on these changes especially on thioredoxin system.