Potential Implications of Rimonabant on Age-Related Oxidative Stress and Inflammation.

Renáta Szabó,Anikó Pósa,Rudolf Gesztelyi,Alexandra Hoffmann,Andrea Pálszabó,Denise Börzsei,Patrícia Pálszabó,Zsuzsanna Szabó,Csaba Varga,Zelma Lesi,Szabolcs Dvorácskó,Krisztina Kupai,Dániel Priksz,Béla Juhász,Anita Altmayer

doi:10.3390/antiox11010162

Abstract

Over the last decades, growing interest has turned to preventive and therapeutic approaches for achieving successful aging. Oxidative stress and inflammation are fundamental features of cardiovascular diseases; therefore, potential targets of them can improve cardiac outcomes. Our study aimed to examine the involvement of the endocannabinoid system, especially the CB1 receptor blockade, on inflammatory and oxidant/antioxidant processes. Twenty-month-old female and male Wistar rats were divided into rimonabant-treated and aging control (untreated) groups. Rimonabant, a selective CB1 receptor antagonist, was administered at the dose of 1 mg/kg/day intraperitoneally for 2 weeks. Cardiac amounts of ROS, the antioxidant glutathione and superoxide dismutase (SOD), and the activity and concentration of the heme oxygenase (HO) enzyme were detected. Among inflammatory parameters, nuclear factor-kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), and myeloperoxidase (MPO) enzyme activity were measured. Two weeks of low dose rimonabant treatment significantly reduced the cardiac ROS via boosting of the antioxidant defense mechanisms as regards the HO system, and the SOD and glutathione content. Consistently, the age-related inflammatory response was alleviated. Rimonabant-treated animals showed significantly decreased NF-κB, TNF-α, and MPO levels. Our findings prove the beneficial involvement of CB1 receptor blocker rimonabant on inflammatory and oxidative damages to the aging heart.

Highlights

IntroductionAging is associated with a progressive decline in numerous physiological processes and is considered as an independent and cumulatively factor in the development and progression of cardiovascular diseases (CVDs)
We found that 2-week rimonabant administration significantly decreased the reactive oxygen species (ROS) concentration in both male and female rats, suggesting a beneficial effect of rimonabant on oxidative damage
A growing body of evidence proves that aging-induced oxidative stress and inflammation significantly decrease the heme oxygenase (HO) activity and the expression of HO-1 isoform compared with rats in reproductive age, whereas this diminished level can be compensated by natural or synthetic agents/interventions that possess antioxidant or anti-inflammatory properties [16,22,23]

Summary

Introduction

Aging is associated with a progressive decline in numerous physiological processes and is considered as an independent and cumulatively factor in the development and progression of cardiovascular diseases (CVDs). A large number of epidemiological evidence shows that a state of low-grade inflammation, termed inflammaging, makes the heart more vulnerable to cardiovascular injuries [1,2]. Even though the precise etiology and the diverse consequences of inflammaging are not fully elucidated, it is established that 4.0/). Antioxidants 2022, 11, 162 the accumulation of reactive oxygen species (ROS) leads to an imbalance between the antioxidant and oxidative systems, which can be associated with CVDs [3]. There are various signaling mechanisms, which can be associated with systemic and tissue-specific antioxidant properties or even has a significant impact on inflammatory mechanisms.

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