Ulinastatin Administration Research Articles

Protective action of ulinastatin against cisplatin nephrotoxicity in mice and its effect on the lysosomal fragility.

The development of azotemia after cisplatin injection in mice was inhibited by ulinastatin treatment in a dose-dependent manner. Reduction in creatinine clearance and elevation in fractional excretion of sodium in mice receiving cisplatin was ameliorated by ulinastatin administration. Epithelial necrosis and hyaline cast formation in the proximal tubule were also suppressed. Ulinastatin showed no influence on the kidney platinum level after cisplatin injection. In LLC-PK1 cells, addition of ulinastatin to the incubation medium markedly reduced the release of N-acetyl-beta-D-glucosaminidase, on of the lysosomal enzymes, during hypotonic treatment only when cells were damaged with cisplatin. On the other hand, ulinastatin showed no effect on the elevation of malondialdehyde concentration in the murine kidney cortical slices after the treatment with cisplatin. These results indicate that ulinastatin has a protective effect against cisplatin nephrotoxicity, and its prevention of the increase in lysosomal fragility is a probable mechanism involved in the renal protection.

Ulinastatin ameliorates acute ischemic renal injury in rats.

Effects of ulinastatin (a Kunitz-type proteinase inhibitor) administration was examined in a model of acute ischemic renal injury induced by bilateral renal artery occlusion in rats. Compared with rats administered vehicle, rats administered ulinastatin (150,000 U/kg body weight) intravenously 30 min preischemia had significantly lower serum creatinine and blood urea nitrogen, and much less injury evident by examination of kidney histologies over the course of 48 h postreperfusion. We conclude that ulinastatin exerts a protective effect against ischemic renal injury.

The effects of ulinastatin on cardiac and hepatic energy metabolism in rats subjected to hypovolemic shock.

Ulinastatin is a trypsin inhibitor extracted from human urine. In this study the effects of ulinastatin on myocardial and hepatic tissue concentrations of creatine phosphate (CP), ATP, ADP, AMP, lactate, pyruvate, and glycogen have been investigated in rats which were in hemorrhagic shock state. Hypovolemia was induced by bleeding from the femoral artery, and systolic blood pressure was maintained 40 mmHg for 25 min, then ulinastatin 50,000 units.kg(-1) in saline or saline vehicle was intravenously administered. Thereafter the heart and liver were extirpated and frozen quickly with liquid nitrogen. The tissue concentrations of CP, ATP, ADP, AMP, lactate and glycogen were measured enzymatically. Systolic blood pressure elevated significantly after ulinastatin administration. The myocardial tissue CP level was higher in ulinastatin-treated group than that of control group, whereas no significant difference in energy charge between two groups. The hepatic tissue level of AMP, lactate and L/P ratio was lower in ulinastatin-treated group than that of control group, however, no significant difference was found in hepatic tissue level of ATP, ADP and energy charge. From these results it is concluded that ulinastatin can improve the energy metabolism of myocardium to some extent, but not of the liver in rats with hypovolemic shock.