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Betulinic acid attenuates lipopolysaccharide-induced vascular hyporeactivity in the rat aorta by modulating Nrf2 antioxidative function
- Source :
- Inflammopharmacology. 28:165-174
- Publication Year :
- 2019
- Publisher :
- Springer Science and Business Media LLC, 2019.
-
Abstract
- Betulinic acid (BA), a pentacyclic triterpenoid, has been reported to inhibit cardiovascular dysfunction under sepsis-induced oxidative stress. Nuclear factor erythroid-2 related factor-2 (Nrf2) is regarded as a key transcription factor regulating expression of endogenous antioxidative genes. To explore the preventive effects of BA against vascular hyporeactivity and the related antioxidative mechanism in sepsis, contraction and relaxation in aortas isolated from lipopolysaccharide (LPS)-challenged rats were performed. Male Sprague–Dawley rats were pretreated with brusatol (Bru, 0.4 mg/kg/2 days, i.p.), an inhibitor of Nrf2, and BA (10, 25, 50 mg/kg/day, i.g.) for 3 days and injected with LPS (10 mg/kg, i.p.) at the 4th day. Rats were anesthetized and killed by cervical dislocation after they were treated with LPS for 4 h. Thoracic aortas were immediately dissected out to determine contraction and relaxation using the organ bath system. Pro-inflammatory factors interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) and oxidative stress were measured in aortic tissues and plasma. mRNA expression of Nrf2-regulated antioxidative enzymes, including superoxide dismutase (SOD), glutathione peroxidase (GPx), and heme oxygenase-1 (HO-1), in rat aortas was determined. Increases of IL-1β, TNF-α, nitric oxide, and malondialdehyde and the decrease of glutathione induced by LPS were significantly attenuated by pretreatment with different doses of BA in plasma and aortas (p
- Subjects :
- Lipopolysaccharides
Male
0301 basic medicine
medicine.medical_specialty
Contraction (grammar)
NF-E2-Related Factor 2
Interleukin-1beta
Immunology
Aorta, Thoracic
Nitric Oxide
medicine.disease_cause
Antioxidants
Nitric oxide
Rats, Sprague-Dawley
Superoxide dismutase
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Malondialdehyde
Internal medicine
medicine
Animals
Pharmacology (medical)
Betulinic Acid
Phenylephrine
Pharmacology
chemistry.chemical_classification
biology
Superoxide Dismutase
Tumor Necrosis Factor-alpha
Glutathione peroxidase
NF-kappa B
Glutathione
Triterpenes
Rats
Oxidative Stress
030104 developmental biology
Endocrinology
chemistry
biology.protein
Pentacyclic Triterpenes
030217 neurology & neurosurgery
Oxidative stress
medicine.drug
Subjects
Details
- ISSN :
- 15685608 and 09254692
- Volume :
- 28
- Database :
- OpenAIRE
- Journal :
- Inflammopharmacology
- Accession number :
- edsair.doi.dedup.....85c4f42c71cef5e5b21a05939fc19dc5