Comparative nephroprotective efficacy of malonic acid derivatives (etmaben and maloben) in renal ischemia-reperfusion injury in rats

Introduction. This study assessed the nephroprotective potential of malonic acid derivatives (MADs) in acute and subacute ischemic renal injury. A model of prerenal failure was simulated using 60-minute warm renal ischemia. Aim. To study the nephroprotective effect of MADs in acute and subacute ischemic renal failure. Materials and methods. The experiment was conducted using a model of warm renal ischemia induced by 60-minute occlusion of the right renal artery. During a month-long monotherapy course, the effects of 4-[(3-ethoxy-3-oxopropanoyl) amino]benzoic acid (etmaben, 60 mg/kg) and sodium 4,4'-(propanediamido)dibenzoate (maloben, 60 mg/kg) were compared with the reference drug, ethylmethylhydroxypyridine succinate (Mexidol®, 50 mg/kg). To assess renal function on days 3 and 30 after ischemia, serum creatinine and urea concentrations, glomerular filtration rate (GFR), creatinine clearance, electrolyte excretion rate, and antioxidant gene expression were analyzed, and histological examination was performed. Results and discussion. The obtained data indicate the significant efficacy of MADs in the treatment of acute ischemic kidney injury. In the group of animals receiving etmaben, a statistically significant decrease in serum creatinine and urea levels, as well as an increase in glomerular filtration rate, was observed, with no significant effect on diuresis. Maloben, in turn, had a more pronounced effect on diuresis and electrolyte excretion during the acute period. Both studied compounds demonstrated the ability to improve renal excretory function, manifested by increased creatinine elimination and a reduction in the severity of the oligoanuric phase of acute nephropathy. Conclusion. It was found that the studied drugs activate renal excretory function, contribute to the normalization of creatinine clearance and the attenuation of the manifestations of acute oligoanuric syndrome, stabilizing the condition of animals with acute kidney injury.