The influence of folic acid-induced acute kidney injury on cardiac function and redox status in rats

Naunyn Schmiedebergs Arch Pharmacol. 2020 Jan;393(1):99-109. doi: 10.1007/s00210-019-01717-z. Epub 2019 Aug 27.

Abstract

The aim of this study was to evaluate the influence of acute kidney injury caused by high doses of folic acid on cardiac function and markers of oxidative stress in serum and isolated rat heart. Isolated hearts of Wistar albino rats (divided into two groups: control and folic acid group) were perfused according to Langendorff technique at basal coronary perfusion pressure CPP of 70 cm H2O. After a stabilization period, CPP was lowered to 60 cm H2O and then gradually increased to 80, 100, 120 and finally decreased to 40 cm H2O in order to establish coronary autoregulation. For each perfusion pressure value, the left ventricular function parameters were determined. Samples of coronary venous effluent were collected for determination of coronary flow and biomarkers of oxidative stress. The blood samples were collected in order to examine the values of serum urea, creatinine, Na, K, and parameters of oxidative stress and antioxidant defense system. Heart and kidney tissue samples were collected for histopathological examination. Folic acid group showed reduction of systolic and diastolic left ventricular pressure and increase of coronary flow and minimum left ventricular pressure development rate. In coronary flow, folic acid group showed increased levels of TBARS and reduction of H2O2 and NO2-. Serum ROS concentrations were lower in rats treated with folic acid, particularly levels of TBARS and NO2- in which values were significantly lower. The parameters of systemic antioxidative stress were at significantly high levels especially SOD and GSH. This study is the experimental confirmation of cardio-renal syndrome type 3, which represents the acute kidney injury that causes a damage of a heart function. The data suggest that negative effects of acute kidney injury on myocardium do not necessarily involve oxidative stress, which may lead to future investigations which will be based on inflammation as a one of the important factors in the organ crosstalk.

Keywords: Acute kidney injury; Cardiac function; Folic acid; Oxidative stress.

MeSH terms

  • Acute Kidney Injury / chemically induced*
  • Acute Kidney Injury / metabolism
  • Acute Kidney Injury / pathology
  • Acute Kidney Injury / physiopathology*
  • Animals
  • Coronary Circulation / drug effects
  • Folic Acid*
  • Heart / physiopathology*
  • Heart Rate / drug effects
  • Hydrogen Peroxide / metabolism
  • Kidney / drug effects
  • Kidney / pathology
  • Male
  • Myocardium / pathology
  • Nitrites / metabolism
  • Oxidation-Reduction
  • Oxidative Stress / drug effects
  • Rats, Wistar
  • Superoxides / metabolism
  • Thiobarbituric Acid Reactive Substances / metabolism
  • Ventricular Function / drug effects

Substances

  • Nitrites
  • Thiobarbituric Acid Reactive Substances
  • Superoxides
  • Folic Acid
  • Hydrogen Peroxide