Normobaric hyperoxia plays a protective role against renal ischemia-reperfusion injury by activating the Nrf2/HO-1 signaling pathway
Autor: | Shuxiong Xu, Mei Feng, Yuangao Xu, Hua Shi, Wang Yuanlin, Shuyu Cai, Shang Song, Fa Sun, Guangheng Luo, Jun Pei |
---|---|
Rok vydání: | 2020 |
Předmět: |
Male
0301 basic medicine Antioxidant NF-E2-Related Factor 2 medicine.medical_treatment Biophysics Protoporphyrins Apoptosis Hyperoxia Pharmacology Kidney medicine.disease_cause Biochemistry Antioxidants Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Animals Enzyme Inhibitors Molecular Biology Inhalation Renal ischemia business.industry Zinc protoporphyrin Cell Biology Rats Disease Models Animal Oxidative Stress Atmospheric Pressure 030104 developmental biology medicine.anatomical_structure chemistry Reperfusion Injury 030220 oncology & carcinogenesis Heme Oxygenase (Decyclizing) Signal transduction business Oxidative stress Signal Transduction |
Zdroj: | Biochemical and Biophysical Research Communications. 532:151-158 |
ISSN: | 0006-291X |
Popis: | Following renal ischemia-reperfusion injury (RIRI), because of the decrease in oxygen supply to the kidney, a large amount of oxygen-free radicals is generated, and in severe cases, tissue cells will undergo apoptosis or even die. Normobaric hyperoxia (NBHO) is a very common clinical adjuvant treatment. It restores the oxygen supply after renal ischemia and combats oxidative stress in tissues, thus playing a protective role. In this study, our aim is to elucidate the protective mechanism of NBHO inhalation in a rat RIRI model. We performed a surgical excision of the left kidney of the rat and established a right kidney solitary kidney model. Later, the right renal pedicle of the rat was clamped using a non-invasive vascular clamp for 45 min. After the vascular clamp was released and reperfused for 24 h, the rat was placed in a closed oxygen chamber. It was subjected to inhalation of high-concentration oxygen (50%–55%), 2 h daily, for 7 days.RIRI induces postoperative weight loss, impaired renal function, increased oxygen free radicals, reduced antioxidant substances, increased histopathological damage, and increased levels of apoptosis. These effects were significantly improved after treatment with NBHO. At the same time, NBHO significantly increased the expression levels of Nrf2 and HO-1 in the tissues after RIRI. To verify whether HO-1 induced by Nrf2 is involved in the resistance to oxidative stress, after the rat RIRI and before inhaling NBHO, we intraperitoneally injected HO-1 specific inhibitor zinc protoporphyrin (ZnPP) (45 μmol/Kg). However, we found that ZnPP reversed the protective effect of NBHO on RIRI in rats. Combining all the results, we have demonstrated the protective effect of NBHO on RIRI, which can be at least partially attributed to the activation of the Nrf2/HO-1 antioxidative stress pathway. |
Databáze: | OpenAIRE |
Externí odkaz: |