Involvement of NADPH-oxidase enzyme in the nephroprotective effect of (−)-α-bisabolol on HK2 cells exposed to ischemia – Reoxygenation
| Autor: | Tiago Lima Sampaio, Emanuel Paula Magalhães, Márcia Machado Marinho, Ricardo Pires dos Santos, Alice Maria Costa Martins, Isabella Evelyn Prado de Azevedo, Dânya Bandeira Lima, Rose Anny Costa Silva, Ramon Róseo Paula Pessoa Bezerra de Menezes |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cell Survival Apoptosis Pharmacology medicine.disease_cause Thiobarbituric Acid Reactive Substances Cell Line 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Humans Hepatitis A Virus Cellular Receptor 1 Viability assay Cell damage Bisabolol chemistry.chemical_classification Reactive oxygen species NADPH oxidase biology NADPH Oxidases NOX4 medicine.disease Glutathione Monocyclic Sesquiterpenes Oxygen Oxidative Stress Kidney Tubules 030104 developmental biology chemistry Cytoprotection Reperfusion Injury biology.protein Reactive Oxygen Species 030217 neurology & neurosurgery Oxidative stress |
| Zdroj: | European Journal of Pharmacology. 855:1-9 |
| ISSN: | 0014-2999 |
| Popis: | Acute Kidney Injury (AKI) is associated with high morbidity and mortality. Ischemia and reperfusion (I/R) are events that lead to AKI through hypoxia, reactive oxygen species (ROS) production, oxidative stress and apoptosis. We aimed to evaluate the mechanism of nephroprotection mediated by Bisabolol in human tubular kidney cells after injury by I/R in vitro. HK2 cells were exposed to I/R and treated with Bisabolol. Cell viability was accessed by MTT assay. Cells were submitted to flow cytometry to evaluate necrotic/apoptotic cells, reactive oxygen species production and mitochondrial transmembrane depolarization. TBARS and GSH were used as parameters of redox balance. Also, KIM-1 supernatant levels were measured. In order to identify an interaction between bisabolol and NOX4, molecular docking and enzymatic assays were performed. Expression of isoform NOX4 on treated cells was examined by western-blot. Finally, cells were visualized by scanning electron microscopy. Bisabolol improved cell viability and prevented cell death by apoptosis, indicated also by the decreased levels of KIM-1. It was observed a decrease on reactive oxygen species production and mitochondrial depolarization, with antioxidant regulation by increased GSH and decreased lipid peroxidation. It was also demonstrated that bisabolol treatment can inhibit NOX4. Finally, SEM images showed that bisabolol reduced I/R-induced cell damage. Bisabolol treatment protects HK2 cells against oxidative damage occasioned by I/R. This effect is related to inhibition of apoptosis, decrease on KIM-1 release, reactive oxygen species accumulation and mitochondrial dysfunction. Bisabolol inhibited NOX4 activity in the tubular cells, impairing reactive oxygen species synthesis. |
| Databáze: | OpenAIRE |
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