In vivo protective effect of betulinic acid on dexamethasone induced thymocyte apoptosis by reducing oxidative stress
| Autor: | Jianping Wu, Jing Wu, Ruocen Zhu, Weiwei Jiang, Jine Yi, Siting Xiang, Zhuliang Tan, Wei Xia, Lijuan Zhu |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Programmed cell death medicine.medical_specialty Antioxidant medicine.medical_treatment Apoptosis Biology Protective Agents medicine.disease_cause Antioxidants Dexamethasone Lipid peroxidation Mice 03 medical and health sciences chemistry.chemical_compound Betulinic acid Internal medicine medicine Animals Betulinic Acid Glucocorticoids Cell Proliferation Pharmacology chemistry.chemical_classification Reactive oxygen species Thymocytes Dose-Response Relationship Drug General Medicine Triterpenes Oxidative Stress 030104 developmental biology Endocrinology chemistry Pentacyclic Triterpenes Reactive Oxygen Species Glucocorticoid Oxidative stress medicine.drug |
| Zdroj: | Pharmacological Reports. 68:95-100 |
| ISSN: | 1734-1140 |
| Popis: | Background Dexamethasone (Dex), a synthetic glucocorticoid, is strictly controlled for use due to its serious side effects, including immune suppression. Betulinic acid (BA), an antioxidant prepared from the white birch, exhibits immunomodulation properties. To assess the implications and investigate the mechanisms of BA-elicited immunomodulation, we hypothesized that Dex induced thymocyte apoptosis via oxidative stress could be lessened by BA. Methods Mice were given oral doses of BA (0.25, 0.5, and 1.0 mg/kg) daily for 14 days, and induced oxidative stress by giving a single dose of Dex intraperitoneal at the dosage of 25 mg/kg body weight 8 h after the last administration of BA. Results Dex administration alone significantly decreased antioxidant enzyme activities, while significantly increased reactive oxygen species (ROS) production, lipid peroxidation, mitochondrial dysfunctions, caspase-3 activation and cellular apoptosis. However, pretreatment with BA dose-dependently mitigated Dex-induced oxidative damage after 14 days of feeding. In addition to ROS scavenging activity in Dex-induced thymocyte, BA administration decreased lipid peroxidation, up-regulated antioxidant enzymes, restored mitochondrial function, increased Bcl-2 expression but reduced Bax expression, inhibited caspase-3 activation, and improved cell survival. Conclusions These findings reveal a protective capability of BA against Dex-induced cell death by reducing oxidative stress via mitochondrial mediated signal pathway which could be the potential mechanism underlying BA-elicited immunomodulation. |
| Databáze: | OpenAIRE |
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