Impact of allogeneic fetal tissue cryoextract on kidney structure and functions when simulating the muscle injuries in rats

Abstract

Rhabdomyolysis is one of the most common causes of acute kidney injury (AKI). Pharmacological correction of AKI has still remained poorly developed, that requires finding the new approaches to its therapy and prevention, particularly, using the biologically active compounds of fetoplacental origin. Here, we have studied the nature of structural changes in renal tissue and biochemical parameters of blood and urine in rats in the model of traumatic rhabdomyolysis, as well as after administering the allogeneic CryoExtract of Fetal Tissues (CEFT) as a preventive measure. Contusion was simulated by blunt, non-penetrating impact of a heavy steel ball on the muscles of both thighs of rats under injectable anesthesia. CEFT was administered intramuscularly in a dose of 0.5 ml thrice during the week before the injury. In 1, 3, 7, 14 days after injury, animals were sacrificed and the material was collected. Simulated contusion resulted in a 1.5-fold increase in concentration of creatine kinase and was accompanied by AKI development, manifested in proteinuria, a 1.5-fold rise in creatinine level, decreased urinary creatinine and diuresis, and a 4.5-fold reduction of glomerular filtration rate. Structural changes in renal tissues were represented by tubular nephropathy with necrosis of epitheliocytes, the presence of myoglobin cylinders in the lumen of tubules of cortex and medulla, venous hyperemia, interstitial edema, and lymphocyte-macrophage infiltration. After 7 and 14 days, the parameters of excretory function of the kidneys improved, without reaching the level of intact rats. Preventive administration of CEFT promoted the weakening of AKI development within the first 3 days and restoration of excretory function in 7 days after the injury. The concentration of creatine kinase increased 1.16 times after 1 day, and did not differ from the norm later. After 7 days, the percentage of altered cells of renal tubules decreased, and no cylinders in the lumens were detected. The structure of renal tissue was normalized after 14 days. The dynamics of parameters of morphofunctional state of the kidneys revealed a nephroprotective effect of CEFT. Keywords: rhabdomyolysis, acute kidney injury, kidney tissue structure.