Chrysin ameliorates ANTU‐induced pulmonary edema and pulmonary arterial hypertension via modulation of VEGF and eNOs
| Autor: | Ye Wang, Zhang Lei, Linlin Wang |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Male
Vascular Endothelial Growth Factor A 0301 basic medicine medicine.medical_specialty Nitric Oxide Synthase Type III Hypertension Pulmonary Health Toxicology and Mutagenesis Aspartate transaminase Pulmonary Edema alpha-Naphthylthiourea Pulmonary Artery Toxicology Biochemistry Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine Lactate dehydrogenase medicine Animals Chrysin Lung Molecular Biology Flavonoids 030102 biochemistry & molecular biology medicine.diagnostic_test biology Thiourea General Medicine Pulmonary edema medicine.disease Rats Bronchoalveolar lavage Endocrinology medicine.anatomical_structure chemistry Alanine transaminase 030220 oncology & carcinogenesis biology.protein Molecular Medicine |
| Zdroj: | Journal of Biochemical and Molecular Toxicology. 33 |
| ISSN: | 1099-0461 1095-6670 |
| DOI: | 10.1002/jbt.22332 |
| Popis: | Alpha-naphthylthiourea (ANTU), a rodenticide induces lung toxicity. Chrysin a flavonoid possesses antioxidant, anti-inflammatory, and antihypertensive potential. The aim of this study was to evaluate the efficacy of chrysin against ANTU-induced pulmonary edema (PE) and pulmonary arterial hypertension (PAH) in laboratory rats. Sprague-Dawley rats were used to induce PE (ANTU, 10 mg/kg, ip) and PAH (ANTU, 5 mg/kg, ip, 4 weeks). Animals were treated with chrysin (10, 20, and 40 mg/kg) and various biochemical, molecular, and histological parameters were evaluated. Acute administration of ANTU induces PE revealed by significant (P < 0.05) increase in relative lung weight, pleural effusion volume, lung edema, bronchoalveolar lavage fluid cell counts, total protein, 5-hydroxytryptamine (5-HT), lactate dehydrogenase (LDH), and γ-glutamyl transferase (GGT), whereas pretreatment with chrysin (20 and 40 mg/kg, ip) significantly (P < 0.05) attenuated these ANTU-induced biochemical and histological alterations. Repeated administration of ANTU caused induction of PAH evaluated by significant (P < 0.05) alterations in electrocardiographic, hemodynamic changes, and left ventricular function, whereas chrysin (20 and 40 mg/kg, p.o.) treatment significantly (P < 0.05) attenuated these alterations. ANTU-induced hematological and serum biochemical (aspartate transaminase, alanine transaminase, LDH, and creatinine kinase MB) alterations were significantly (P < 0.05) inhibited by chrysin. It also significantly (P < 0.05) decreased elevated levels of oxido-nitrosative stress in the right ventricle (RV) and lung. Chrysin significantly (P < 0.05) attenuated downregulated endothelial nitric oxide synthase and upregulated vascular endothelial growth factor messenger RNA and protein expressions both in the RV and pulmonary artery. Chrysin inhibited ANTU-induced PE and PAH via modulation of inflammatory responses (5-HT, LDH, and GGT), oxido-nitrosative stress, and VEGF and eNOs levels. |
| Databáze: | OpenAIRE |
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