Logo: to the web site of Uppsala University

uu.sePublications from Uppsala University
System disruptions
There are recurring service disruptions on some of the search portals due to high traffic. We are working to resolve the issue, you may temporarily encounter an error message.
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Myrcene Attenuates Renal Inflammation and Oxidative Stress in the Adrenalectomized Rat Model
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. United Arab Emirates Univ, Coll Med & Hlth Sci, Dept Pharmacol & Therapeut, Al Ain 17666, U Arab Emirates.ORCID iD: 0000-0002-0788-7164
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.ORCID iD: 0000-0002-7142-3479
United Arab Emirates Univ, Coll Med & Hlth Sci, Dept Pharmacol & Therapeut, Al Ain 17666, U Arab Emirates.ORCID iD: 0000-0003-2141-3210
Show others and affiliations
2020 (English)In: Molecules, ISSN 1431-5157, E-ISSN 1420-3049, Vol. 25, no 19, article id 4492Article in journal (Refereed) Published
Abstract [en]

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-1 beta, IL-6, and TNF-alpha) compared to untreated ADX rats. In addition, myrcene resulted in significant downregulation of immunomodulatory factors (IFN gamma and NF-kappa B) 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.

Place, publisher, year, edition, pages
MDPI, 2020. Vol. 25, no 19, article id 4492
Keywords [en]
glucocorticoids, adrenalectomy, inflammation, oxidative stress, Th1 and Th2 cytokines, kidney injury molecule
National Category
Physiology and Anatomy
Identifiers
URN: urn:nbn:se:uu:diva-426352DOI: 10.3390/molecules25194492ISI: 000587249500001PubMedID: 33007969Scopus ID: 2-s2.0-85092543092OAI: oai:DiVA.org:uu-426352DiVA, id: diva2:1505310
Available from: 2020-11-30 Created: 2020-11-30 Last updated: 2025-10-09Bibliographically approved
In thesis
1. Role of β-myrcene in attenuation of neurodegeneration, renal malfunction, and Inflammatory bowel disease in the Adrenalectomized Rat model
Open this publication in new window or tab >>Role of β-myrcene in attenuation of neurodegeneration, renal malfunction, and Inflammatory bowel disease in the Adrenalectomized Rat model
2024 (English)Doctoral thesis, comprehensive summary (Other academic) [Artistic work]
Abstract [en]

Glucocorticoids (GCs) are secreted by the adrenal glands in response to signals from the hypothalamus and pituitary gland through the hypothalamic–pituitary–adrenal axis. Physiological GCs are important regulators of immunity, energy metabolism, oxidative stress response, and cellular homeostasis.

Adrenalectomy (ADX) results in the loss of hippocampal neurons including the dentate gyrus, and cornu ammonis. Pathways implicated in neurodegeneration include inflammation, upregulation of microglia and astrocytes, oxidative stress, downregulation of autophagy, disruption of cellular homeostasis, and increased apoptosis. The autophagy lysosomal pathway plays a pivotal role in the degradation of damaged organelles and retrieval of proteins essential for the cell cycle and intracellular homeostasis. Metabolism and homeostasis in the hippocampal neurons are mediated by the mammalian target of rapamycin through the autophagy lysosomal pathway. Myrcene was evaluated to mitigate inflammation and oxidative stress and reinstate metabolism and cellular homeostasis. Myrcene attenuated inflammation, deactivated glial cells and astrocytes, relieved oxidative stress, reinstated autophagy, promoted hippocampal neuronal growth, ensured homeostasis, and prevented apoptosis in adrenalectomized rats.

ADX-mediated GC depletion mediated renal inflammation, induced oxidative stress, and exacerbated renal injury, leading to functional impairment and increased mortality in inflammatory bowel disease (IBD). Meanwhile, myrcene abrogated the inflammatory plethora and inhibited reactive oxygen species (ROS), ultimately preventing renal injury and reducing mortality in adrenalectomized rats with IBD. Furthermore, in ADX-induced inflammation and oxidative stress, myrcene attenuated renal inflammation and inhibited ROS. ADX promotes the recruitment of macrophages in the kidney, which exacerbates inflammation and oxidative stress, ultimately leading to the impairment of renal function. Myrcene attenuated renal inflammation and oxidative stress, reinstating the renal function, in ADX-treated rats.

Overall, myrcene prevents neurodegeneration, improves renal function, and mitigates IBD complications, exhibiting potency in alleviating neuronal and renal inflammation and oxidative stress. 

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2024. p. 109
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 359
Keywords
Glucocorticoids, Adrenalectomy, Hypothalamus-pituitary-adrenal axis, Reactive oxygen species, Nitric oxide, Malondialdehyde, Glutathione, Catalase, Sodium oxide dismutase, Cyclooxygenase-2, Inducible nitric oxide synthases, Nuclear factor-κB, Mammalian target of rapamycin, p70S6, LMAP2, MMP-9, LC3, Bcl-2, Kidney injury molele-1, IBD, Crohn's disease, Ulcerative colitis, Myeloperoxidase
National Category
Medical and Health Sciences
Research subject
Medical Science
Identifiers
urn:nbn:se:uu:diva-537487 (URN)978-91-513-2218-6 (ISBN)
Public defence
2024-10-18, C4:301, BMC, Husargatan 3, Uppsala, 14:00 (English)
Opponent
Supervisors
Projects
no
Available from: 2024-09-27 Created: 2024-09-02 Last updated: 2024-10-18

Open Access in DiVA

fulltext(2759 kB)498 downloads
File information
File name FULLTEXT01.pdfFile size 2759 kBChecksum SHA-512
20ec5b583c42b3c18e0966b64c77cab4b28fd9e2d681f88f79cacb648b08dc578f5ca5f565ecf8011f201a4c2ced91d7bcbdbd22b62646d2a3f23b565fd4c1f7
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMedScopus

Authority records

Islam, Azim Ullah ShamsulHellman, BjörnNyberg, Fred

Search in DiVA

By author/editor
Islam, Azim Ullah ShamsulHellman, BjörnNyberg, FredAmir, NaheedJayaraj, Richard L.
By organisation
Department of Pharmaceutical Biosciences
In the same journal
Molecules
Physiology and Anatomy

Search outside of DiVA

GoogleGoogle Scholar
Total: 498 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 291 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf