Nephroprotection through Modifying the Apoptotic TNF-α/ERK1/2/Bax Signaling Pathway and Oxidative Stress by Long-term Sodium Hydrosulfide Administration in Ovalbumin-induced Chronic Asthma

ABSTRACT

Asthma is one of the most common respiratory diseases in the world. Nevertheless, it is reported that inflammation induced by asthma is not only restricted to the lung and may cause damaging effects on remote organs. Therefore, this study was designed to investigate the beneficial effects of long-term sodium hydrosulfide (NaHS) administration on lung inflammation and oxidative stress markers to protect the kidney during chronic asthma. BALB/c mice were divided into three groups (n = 5–7): control, asthma and NaHS. Except the control group, sensitization and challenge were performed with ovalbumin. The NaHS group intraperitoneally received 14 μmol/kg NaHS 30 min before each challenge. 24 h after the last challenge, samples of bronchoalveolar lavage fluid (BALF), plasma, lung and kidney tissues were collected. NaHS administration significantly decreased total white blood cell count, percentages of eosinophils, neutrophils and macrophages and increased percentage of lymphocytes. Administration of NaHS considerably decreased the levels of BALF interleukin-13, plasma tumor necrosis factor-alpha (TNF-α), lung malondialdehyde (MDA) and lung phosphorylated nuclear factor-kappa B (p-NF-κB) expression and scores of peribronchial inflammatory cell infiltration, goblet cell hyperplasia and subepithelial fibrosis and increased the activity of lung superoxide dismutase (SOD). The MDA levels and expressions of p-ERK1/2 and Bax were decreased and SOD activity and expressions of Bcl-2 and p-Akt were significantly increased in kidney tissues by NaHS administration. Administration of NaHS decreased renal oxidative stress indices and reduced apoptosis by the inhibition of TNF-α/ERK1/2/Bax. Therefore, H₂S may have an essential role in renal protection during asthma.

KEYWORDS:

• Asthma
• sodium hydrosulfide
• kidney
• inflammation
• oxidative stress
• apoptosis

Disclosure of interest

The authors report no conflict of interest.

Additional information

Funding

This study was supported by research grants from Tehran University of Medical Sciences and Health Services, Iran [36317].