CHARACTERIZATION OF THE EFFECTS OF CELL-FREE CRYOPRESERVED BIOLOGICAL AGENTS ON RENAL FUNCTION IN RATS WITH KETOROLAC-INDUCED NEPHROPATHY

Abstract

Nonsteroidal anti-inflammatory drugs are widely used in clinical practice, yet prolonged exposure can injure the kidneys. Ketorolac is known to provoke acute and subacute impairment of glomerular filtration, fluid retention, and accumulation of nitrogenous metabolites. Cell-free biological products preserved by cryopreservation contain regulatory molecules with the potential to restore renal functions. Evaluating their effects in an experimental model is important for developing effective prevention of drug-induced kidney injury and for identifying safer alternatives to standard supportive therapy. The aim of the study – to assess the impact of cell-free cryopreserved biological products on renal function in rats with ketorolac-induced nephropathy. Materials and methods. The study was conducted in forty-two rats randomized into six groups: intact controls; ketorolac control; ketorolac plus canephron; ketorolac plus placental cryoextract; ketorolac plus splenic cryoextract; ketorolac plus conditioned medium of mesenchymal stem cells. Ketorolac was administered for fourteen days. Biological products were given in five administrations. Daily urine output, blood urea and creatinine concentrations, and glomerular filtration rate were measured. Parametric statistical analysis was performed. Research results and their discussion. The ketorolac-induced kidney injury model produced marked disturbances of excretory and filtration functions. Canephron reduced azotemia, lowered creatinine, and increased glomerular filtration rate, while the rise in urine output showed a positive trend. The placental cryoextract fully restored urine output to the intact level, substantially reduced azotemia, and moderately increased glomerular filtration rate. The splenic cryoextract yielded similar outcomes, with significant decreases in urea and creatinine, a moderate increase in urine output, and a stable improvement in glomerular filtration rate. The most pronounced effect was observed with the conditioned medium of mesenchymal stem cells: urine output exceeded intact values, creatinine approached normal, and glomerular filtration rate matched the reference therapy. These findings indicate that cell-free cryopreserved biological products are promising for correcting drug-induced kidney injury and justify further translational clinical development. Conclusions. Ketorolac induces a reproducible nephropathy characterized by depressed urine output, rising azotemia, and reduced filtration capacity. Placental and splenic cryoextracts and the conditioned medium of mesenchymal stem cells mitigate these toxic changes, with the conditioned medium demonstrating the greatest efficacy under experimental conditions.