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Intermittent hypoxia-induced renal antioxidants and oxidative damage in male mice: hormetic dose response
Weixia Sun1, Xia Yin, Yuehui Wang
1The First Hospital of Jilin University, China and KCHRI at the Department of Pediatrics, University of Louisville, USA.
Abstract:
Obstructive sleep apnea causes cardiovascular disease via chronic intermittent hypoxia (IH), which may be related to oxidative stress. Nuclear factor-erythroid 2-related factor 2 (Nrf2) is an important cellular defense mechanism against oxidative stress by regulating its down-stream multiple antioxidants. The present study was to define whether IH can induce renal pathogenic damage and if so, whether Nrf2 and its down-stream antioxidants are involved in IH-induced pathogenic changes. Mice were culled for exposure to intermittent air as control or IH that consisted of 20.9% O2/ 8% O2 FIO2 alternation cycles (30 episodes per h) with 20 seconds at the nadir FIO2 for 12 h a day during daylight. Short-term IH exposure (3 - 7 days) induced significant increases in renal inflammatory response and antioxidant levels along with a reduction of the spontaneous content of malondialdehyde while long-term IH exposure (8 weeks) induced a significant decrease of antioxidant levels and significant increases of renal inflammation, oxidative damage, cell death, and fibrosis. This study suggests that IH induces a hormetic response, i.e.: short-term IH exposure is able to induce a protective response to protect the kidney from oxidative damage while long-term IH exposure is able to induce a damage effect on the kidney.
Insights
Intermittent hypoxia (IH) from sleep apnea causes kidney damage. Short-term IH offers protection, but long-term exposure leads to inflammation, oxidative stress, and fibrosis, impacting kidney health.
Area of Science:
- Physiology
- Pathology
- Molecular Biology
Background:
- Obstructive sleep apnea (OSA) is linked to cardiovascular disease through chronic intermittent hypoxia (IH).
- Oxidative stress is a potential mechanism connecting IH and disease.
- Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a key regulator of cellular antioxidant defenses.
Purpose of the Study:
- To investigate if IH induces kidney damage.
- To determine the role of Nrf2 and its downstream antioxidants in IH-induced renal pathology.
Main Methods:
- Mice were exposed to either control conditions (intermittent air) or IH (alternating 20.9% O2/8% O2 cycles).
- Exposure duration varied: short-term (3-7 days) and long-term (8 weeks).
- Renal inflammatory response, antioxidant levels, malondialdehyde, cell death, and fibrosis were assessed.
Main Results:
- Short-term IH increased renal inflammation and antioxidant levels, decreasing malondialdehyde.
- Long-term IH significantly decreased antioxidant levels.
- Long-term IH elevated renal inflammation, oxidative damage, cell death, and fibrosis.
Conclusions:
- IH exhibits a hormetic effect on the kidney.
- Short-term IH may induce a protective response against oxidative damage.
- Prolonged IH exposure results in significant kidney damage, including inflammation and fibrosis.
