Morphofunctional Changes in Kidneys of Rats With Gentamicin-Induced Acute Kidney Injury and Use of Melatonin

Abstract

Aminoglycosides are effective antibiotics, but their accumulation in kidney cortex causes nephrotoxic effects in 20-30% of patients, which significantly limits their use. For this reason, search for the new therapies aimed at prevention of gentamicin-induced acute kidney injury (AKI) is highly relevant. Thus, the objective of our research was to study the functional and histopathological changes in kidneys of rats with gentamicin-induced AKI, and estimate the renoprotective potential of pineal hormone melatonin, which possesses antioxidant, anti-inflammatory and immunomodulatory effects. The study was conducted on 24 non-linear male rats. Gentamicin-induced AKI was modeled by daily administration of 4% gentamicin sulphate (80 mg/kg) for 6 days. Melatonin (Sigma Aldrich, USA) was injected daily at a dose of 5 mg/kg. Functional state of kidneys was assessed by diuresis, creatinine clearance, urine protein excretion, fractional excretion of sodium, and plasma potassium level. Documentation of the pathological processes was performed by the computer morphometry of objects in histological preparations. Statistical analysis of the data was performed using SPSS 17.0 software. Administration of gentamicin resulted in a significant impairment of renal function of experimental animals. A decrease in creatinine clearance by 3.1 times along with a reduction of diuresis by 1.9 times, and an increase in plasma creatinine concentration by 2.6 times was observed. There also was an increase in urine protein level by 5.2 times, an elevation of fractional sodium excretion and a reduction of plasma potassium level. Use of melatonin caused a significant improvement of renal function comparing to model pathology group. Functional disturbances were accompanied with the significant histopathological changes in kidney tissue: necrosis of the 27±5.2% epithelial cells of proximal tubules with the signs of hydropic vacuolization (7±2.1%) or reversible hydropic swelling (76±1.5%) in the rest of cells; swelling or deformation of some glomeruli. In the medulla tubular lumen were dilated and partially filled with hyaline casts, tubular cells had signs of dystrophy. Use of melatonin contributed to the restraint of the histopathological changes, confirmed by the decrease of the prevalence and severity of tubular necrosis (1.2%), dystrophy (64±2.3%), and injury of glomeruli. Obtained results verify the significant nephroprotective effect of pineal hormone melatonin, providing a background for the further in-depth study of its renal effects as well as its prospects as a nephroprotector.