Kidney ischemia-reperfusion decreases hydrogen sulfide and increases oxidative stress in the heart
Citation
Wijerathne, C.U.B., Hewage, S.M., Siow, Y.L., Karmin, O. (2020). Kidney ischemia-reperfusion decreases hydrogen sulfide and increases oxidative stress in the heart. Biomolecules, [online] 10(11), 1-13. http://dx.doi.org/10.3390/biom10111565
Plain language summary
Acute kidney injury is a type of kidney failure that occurs within a short period of time and frequently results in death when it occurs in critically ill patients. Blockade of blood vessels leading to the kidneys can cause acute kidney injury, which in turn, can cause damage to other critical organs in the body including the heart. In this study, when blood vessels to the kidneys of both male and female rats were blocked, the heart exhibited an increased level of oxidative stress, indicated by the increased level of oxidized lipids and a decrease in the level of endogenous antioxidants, glutathione and hydrogen sulfide. Evidence for an inhibition of the enzyme responsible for production of the antioxidants in the heart was presented. There was no significant difference in the any of the parameters measured. The results of this study demonstrated for the first time a probable mechanism by which acute kidney injury could damage the heart.
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 (H2 S), at physiological concentrations, has been implicated in cardiovascular protection through redox balance and vessel relaxation. Cystathionine gamma-lyase (CSE) plays an essential role in H2 S production in the heart. The present study investigated the effect of AKI on H2 S 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 H2 S 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 H2 S production, reduce glutathione levels and increase oxidative stress in the heart. This may contribute to an increased risk of cardiovascular disease in AKI.