ORIGINAL ARTICLE The influence of folic acid-induced acute kidney injury on cardiac function and redox status in rats Tomislav Nikolic 1 & Dejan Petrovic 1 & Stevan Matic 2 & Tamara Nikolic Turnic 3 & Jovana Jeremic 3 & Katarina Radonjic 3 & Ivan Srejovic 4 & Vladimir Zivkovic 4 & Stefani Bolevich 5 & Sergey Bolevich 6 & Vladimir Jakovljevic 4,6 Received: 8 July 2019 /Accepted: 16 August 2019 # Springer-Verlag GmbH Germany, part of Springer Nature 2019 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 H 2 O. After a stabilization period, CPP was lowered to 60 cm H 2 O and then gradually increased to 80, 100, 120 and finally decreased to 40 cm H 2 O 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 H 2 O 2 and NO 2 -. Serum ROS concentrations were lower in rats treated with folic acid, particularly levels of TBARS and NO 2 - 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 . Folic acid . Oxidative stress . Cardiac function Introduction Acute kidney injury is a sudden and potentially reversible reduction of renal function which is manifested by an increase in serum levels of nitrogenous end products of metabolism (urea and creatinine). Acute kidney injury (AKI) is a broad clinical entity that includes diverse and often overlapping pathophysiological mechanisms with heterogeneous function- al and morphological characteristics (Makris and Spanou 2016). Among the agents that exhibit nephrotoxicity are nu- merous medications used in everyday clinical practice such as gentamicin, cisplatin, nonsteroidal anti-inflammatory drugs, radiocontrast agents, folic acid, and many others. Drugs cause about 20% of hospital and extrinsic acute kidney damage (Heyman et al. 2009). About 20% of hospital and nonhospital kidney damages are caused by drugs (Uchino 2006). * Tomislav Nikolic nikolic.s.tomislav@gmail.com 1 Faculty of Medical Sciences, Department of Internal medicine, University of Kragujevac, Kragujevac, Serbia 2 Department for Pathological Anatomical Diagnosis, Clinical Center “Kragujevac”, Kragujevac, Serbia 3 Faculty of Medical Sciences, Department of Pharmacy, University of Kragujevac, Kragujevac, Serbia 4 Faculty of Medical Sciences, Department of Physiology, University of Kragujevac, Kragujevac, Serbia 5 Russian Federation, Department of Pathophysiology, 1st Moscow State Medical University IM Sechenov, Moscow, Russia 6 Russian Federation, Department of Human Pathology, 1st Moscow State Medical University IM Sechenov, Moscow, Russia Naunyn-Schmiedeberg's Archives of Pharmacology https://doi.org/10.1007/s00210-019-01717-z