Betulinic acid attenuates lipopolysaccharide-induced vascular hyporeactivity in the rat aorta by modulating Nrf2 antioxidative function
| Autor: | Wei-Xin Li, Xin-Ru Zhou, Chi Xiao, Yao-Yao Bai, Ling-Bo Qian, Dong Yan, Yang-Yun Lou, Hui-Ying Zhou |
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| Rok vydání: | 2019 |
| Předmět: |
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 |
| Zdroj: | Inflammopharmacology. 28:165-174 |
| ISSN: | 1568-5608 0925-4692 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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