Metabolomics Assessment of Volume Overload-Induced Heart Failure and Oxidative Stress in the Kidney

Abstract

The incidence of heart failure (HF) is increasing and is associated with a poor prognosis. Moreover, HF often coexists with renal dysfunction and is associated with a worsened outcome. In many experimental studies on cardiac dysfunction, the function of other organs was either not addressed or did not show any decline. Until now, the exact mechanisms for initiating and sustaining this interaction are still unknown. The objective of this study is to use volume overload to induce cardiac hypertrophy and HF in aortocaval fistula (ACF) rat models, and to elucidate how volume overload affects metabolic changes in the kidney, even with normal renal function, in HF. The results showed the metabolic changes between control and ACF rats, including taurine metabolism; purine metabolism; glycine, serine, and threonine metabolism; glycerophospholipid metabolism; and histidine metabolism. Increasing the downstream purine metabolism from inosine to uric acid in the kidneys of ACF rats induced oxidative stress through xanthine oxidase. This result was consistent with HK-2 cells treated with xanthine and xanthine oxidase. Under oxidative stress, taurine accumulation was observed in ACF rats, indicating increased activity of the hypotaurine–taurine pathway as a defense mechanism against oxidative stress in the kidney. Another antioxidant, ascorbic acid 2-sulfate, showed lower levels in ACF rats, indicating that the kidneys experience elevated oxidative stress due to volume overload and HF. In summary, metabolic profiles are more sensitive than clinical parameters in reacting to damage to the kidney in HF.

Therapies for Cirrhotic Cardiomyopathy: Current Perspectives and Future Possibilities

“…Taurine possesses multiple functions, including the modulation of protein phosphorylation, calcium ion regulation, membrane stabilization, bile acid conjugation, lipid metabolism, glucose regulation, antioxidation, anti-inflammation, and anti-apoptosis [ 53 , 54 ]. It is an abundant amino-sulfonic acid in many tissues, such as skeletal muscle, liver, platelets, and leukocytes, especially in electrically excitable tissues, such as the heart [ 54 ].…”

Effects of immune cells on ischemic stroke and the mediating roles of metabolites

“…In contrast, elevated levels of AA2S may suggest excessive AA depletion, which in turn increases the risk of IS ( 31 , 32 ). Earlier Mendelian randomization studies revealed causal effects of AA2S levels on 26 disease traits across 12 categories in humans ( 33 ). However, this study did not identify a relationship between AA2S levels and IS.…”