Probucol Protects Rats from Cardiac Dysfunction Induced by Oxidative Stress following Cardiopulmonary Resuscitation

Abstract

Objective To investigate the protective effect of probucol on induced cardiac arrest (CA) rats and possible mechanisms. Methods Sprague Dawley rats were orally administrated with probucol at different dosage or vehicle for 5 days and subjected to a CA model by electrical stimulation, followed by cardiopulmonary resuscitation (CPR). The return of spontaneous circulation (ROSC) rate, antioxidant enzyme activities, and lipid oxidation markers were measured in serum and myocardium. Hemodynamic parameters and myocardial functions of animals were analyzed. Expression of erythroid-derived 2-like 2 (NFE2L2) and Kelch-like ECH-associated protein 1 (KEAP1) in the myocardium were examined with immunohistochemistry. Results Probucol treatment significantly increased the ROSC rate and survival time of CA-induced rats. After ROSC, levels of oxidation-specific markers were decreased, while activities of antioxidant enzymes were increased significantly in probucol treatment groups. The probucol treatment improves hemodynamic parameters and myocardial functions. These parameter changes were in a dose-dependent manner. In the probucol treatment groups, the expression of KEAP1 was downregulated, while that of NFE2L2 was upregulated significantly. Conclusion In the CA-induced rat model, probucol dose dependently improved the ROSC rate, prolonged survival time, alleviated oxidative stress, and improved cardiac function. Such protective effects are possibly through regulations of the KEAP1-NFE2L2 system.

Probucol enhances the therapeutic efficiency of mesenchymal stem cells in the treatment of erectile dysfunction in diabetic rats by prolonging their survival time via Nrf2 pathway

“…Probucol has been used as anti-atherosclerotic for many years for its affection on anti-inflammatory and anti-oxidative. According to these pharmacological activities, probucol has been used in the treatment of DMED [9,10]. Our previous study found that probucol can improve erectile function in diabetic rats, which may be related to activation of Nrf2 pathway [11].…”

Probucol Prevents Diabetes-Induced Retinal Neuronal Degeneration through Upregulating Nrf2

“…Probucol is a lipid-lowering drug which increases the fraction rate of LDL catabolism and has been used to treat hyperlipidemia [24]. e antioxidant and anti-inflammatory properties of probucol have been investigated using in vitro cell cultures and in vivo animal models [13,14]. It inhibits extracellular ROS and effectively reduces vascular endothelial cell apoptosis caused by oxidative stress damage [25].…”

“…Probucol is a bisphenol compound that functions as a lipid-lowering drug with anti-inflammatory and antioxidant properties and is widely used to lower cholesterol and reduce atherosclerosis in the clinic [11,12]. ere are certain reports in the literature which indicate that probucol acts as a potent oxygen radical scavenger and thus can effectively prevent oxidative stress-induced tissue damage [13,14]. Duan et al [15] and Yang et al [16] found that probucol can improve the occurrence and development of diabetic nephropathy through antioxidation and protect against diabetic nephropathy.…”

Probucol enhances the therapeutic efficiency of mesenchymal stem cells in the treatment of erectile dysfunction in diabetic rats by prolonging their survival time via Nrf2 pathway

“…As we all know, Probucol has been used as anti-atherosclerotic for many years for its affection on antiinflammatory and anti-oxidative. According to these pharmacological mechanisms, Probucol has been used in treatment of DMED [9,10].Our previous study found that probucol can improve erectile function in diabetic rats, which may be related to activation of Nrf2 pathway. [11] Many studies show that Nrf2 plays a protective role in many pathological processes, including DMED [11,12].…”