Metoprolol and Nebivolol Prevent the Decline of the Redox Status of Low-Molecular-Weight Aminothiols in Blood Plasma of Rats During Acute Cerebral Ischemia

Abstract

Cerebral ischemia has previously been shown to cause a systemic decrease in levels of the reduced forms of low-molecular-weight aminothiols [cysteine (Cys), homocysteine (Hcy), and glutathione (GSH)] in blood plasma. In this study, we examined the effect of beta-adrenergic receptor (β-AR) antagonists metoprolol (Met) and nebivolol (Neb) on the redox status of these aminothiols during acute cerebral ischemia in rats. We used a model of global cerebral ischemia (bilateral occlusion of common carotid arteries with hypotension lasting for 10 minutes). The antagonists were injected 1 hour before surgery. Total and reduced Cys, Hcy, and GSH levels were measured 40 minutes after the start of reperfusion. Neb (0.4 and 4 mg/kg) and Met (8 and 40 mg/kg) treatment increased the levels of reduced aminothiols and the global methylation index in the hippocampus. The treatments also prevented any decrease in reduced aminothiol levels in blood plasma during ischemia. Although both of these drugs eliminated delayed postischemic hypoperfusion, only Neb reduced neuronal damage in the hippocampus. The results indicate an essential role of β1-AR blockage in the maintenance of redox homeostasis of aminothiols in the plasma and brain during acute cerebral ischemia.

Protective effects of nebivolol on ovarian ischemia–reperfusion injury in rat

“…Several studies previously demonstrated important antioxidant effects of NEB and that the administration of NEB increased GSH levels compared to the groups, in which the injury was induced. 17,32 In agreement with previous studies, we observed that GSH levels increased after the prophylactic NEB treatment compared to the case groups in this study.…”

The pretreatment of rats with nebivolol ameliorates bladder contractile dysfunction caused by ischemia‐reperfusion injury

“…Consistent with the present reported data, results from previous studies evaluating the protective effect of nebivolol against IR injury have shown that protection elicited by nebivolol is associated with its antioxidant action. 12,15,24 Accordingly, the present study revealed that nebivolol plays a protective role in the urinary bladder isolated from rats exposed to IR injury, as evident from improvement in the TAS levels, OSI, and contractile function. The alteration in the TAS level of the IR group was significantly different from that of the control or nebivolol +IR groups.…”

“…Previous studies have indicated that nebivolol elicited protection against IR injury in different organs and tissues. [12][13][14][15] To the best of our knowledge, the present study is the first in the literature showing the protective effect of nebivolol on rat urinary bladder contractile dysfunction caused by IR injury. Although therapeutic doses of nebivolol used in the animal models of hypertension range from 5 to 10 mg/kg, lower doses (0.3-2 mg/kg) have also been found to be protective against IR injury.…”

“…15 However, a higher dose (4 mg/kg) of nebivolol failed to produce protection in the same study. 15 Therefore, in the present study, the pretreatment dose of nebivolol (0.4 mg/kg) was especially selected to investigate whether the low dose of nebivolol could also produce protection in a different animal model of IR injury.…”

“…10,11 This notion has also been supported by other studies showing protection with nebivolol against IR injury in several organs and tissues including liver, 12 kidney, 13 heart, 14 and brain. 15 However, there is no study that evaluates the effects of nebivolol against bladder injury induced by IR insult. Therefore, it was set out to obtain further insights into the potential protective effects of nebivolol against IR injury in the rat bladder.…”