Myrcene Attenuates Renal Inflammation and Oxidative Stress in the Adrenalectomized Rat Model

Azim Ullah Shamsul Islam,Abdu Adem,Björn Hellman,Fred Nyberg,Naheed Amir,Richard L Jayaraj,Georg Petroianu

doi:10.3390/molecules25194492

Abstract

Physiological Glucocorticoids are important regulators of the immune system. Pharmacological GCs are in widespread use to treat inflammatory diseases. Adrenalectomy (ADX) has been shown to exacerbate renal injury through inflammation and oxidative stress that results in renal impairment due to depletion of GCs. In this study, the effect of myrcene to attenuate renal inflammation and oxidative stress was evaluated in the adrenalectomized rat model. Rats were adrenalectomized bilaterally or the adrenals were not removed after surgery (sham). Myrcene (50 mg/kg body weight, orally) was administered post ADX. Myrcene treatment resulted in significant downregulation of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) compared to untreated ADX rats. In addition, myrcene resulted in significant downregulation of immunomodulatory factors (IFNγ and NF-κB) and anti-inflammatory markers (IL-4 and IL-10) in treated ADX compared to untreated ADX. Myrcene significantly increased the antioxidant molecules (CAT, GSH, and SOD) and decreased MDA levels in treated ADX compared to untreated. Moreover, myrcene treatment reduced the expression of COX-2, iNOS, KIM-1, and kidney functional molecules (UREA, LDH, total protein, and creatinine) in ADX treated compared to ADX untreated. These results suggest that myrcene could be further developed as a therapeutic drug for treatment of kidney inflammation and injury.

Highlights

Glucocorticoids hereafter (GCs) are important regulators of the immune system, while pharmacological GCs are in widespread use to treat inflammatory diseases
Physiological GCs are pivotal to maintain normal immune system, while pharmacological GCs are in use to suppress the immune system, inflammatory factors [1]
Depletion of GCs (ADX) results in the influx of immune cells, macrophages and NK cells in kidneys, which leads to kidney diseases and other kidney complications [2]

Summary

Introduction

Glucocorticoids hereafter (GCs) are important regulators of the immune system, while pharmacological GCs are in widespread use to treat inflammatory diseases. The major GC in rodents is corticosterone, which is synthesized in the adrenal gland in response to stress or systemic cytokine release [1]. Adrenalectomy hereafter (ADX) has been shown to exacerbate clinical disease and experimental autoimmune encephalomyelitis. Glomerulonephritis (GN) in humans is modulated by pharmacologic doses of steroids, but the role of endogenous GC in the modulation of glomerular injury has not been revealed. Adrenalectomy results in neutrophil influx, which is required for development of renal injury [2]. There has been renewed interest in physiological adrenal GCs and their role in regulating in vivo immune responses. While pharmacological doses are generally immunosuppressive, they may not accurately describe the effects of physiological levels of endogenous

Methods

Results

Conclusion