Abstract
Patients with acute kidney injury (AKI) have an increased risk of cardiovascular disease. The underlying mechanism of AKI-induced heart injury is not well-understood. Hydrogen sulfide (H2S), at physiological concentrations, has been implicated in cardiovascular protection through redox balance and vessel relaxation. Cystathionine gamma-lyase (CSE) plays an essential role in H2S production in the heart. The present study investigated the effect of AKI on H2S production and oxidative stress in the heart. AKI was induced by kidney ischemia-reperfusion in male and female Sprague-Dawley rats, which led to an increase in plasma creatinine and blood urea nitrogen levels. There was a significant increase in lipid peroxidation and a decrease in glutathione (antioxidant) levels in the plasma and heart, indicating systemic and cardiac oxidative stress. Kidney ischemia-reperfusion reduced CSE expression and H2S production in the heart. There was a decrease in antioxidant transcription factor Nrf2 level in the nucleus and an increase in inflammatory cytokine (IL-6, TNF-α) expression in the heart. These results suggest that AKI can down-regulate CSE-mediated H2S production, reduce glutathione levels and increase oxidative stress in the heart. This may contribute to an increased risk of cardiovascular disease in AKI.
Highlights
Acute kidney injury (AKI) is a common clinical condition in critical care settings, characterized by a decline in kidney function, over a short period of time
We investigated the effect of AKI on cardiac H2S production and oxidative stress in male and female rats with kidney ischemia-reperfusion injury
Kidney ischemia-reperfusion caused a significant elevation of plasma creatinine and blood urea nitrogen (BUN) levels in both male and female rats, compared to that in sham-operated rats (Figure 1a,b), indicating impaired kidney function
Summary
Acute kidney injury (AKI) is a common clinical condition in critical care settings, characterized by a decline in kidney function, over a short period of time. Cardiovascular disease represents a main cause of death in AKI patients [4,5]. Our understanding of the molecular pathways that lead to cardiovascular injury and the potential targets for cardiovascular protection in patients with kidney disease is limited. Kidney ischemia-reperfusion injury due to surgical procedures, kidney transplantation or in critically ill patients is one of the most common causes for AKI. Ischemia-reperfusion triggers a series of biochemical and molecular changes that can elicit oxidative stress, inflammation and apoptosis, leading to injuries in the kidneys as well as in the other organs [1,6]
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