Kanamycin の腎毒性に関する生化学的研究

抄録

It has been shown that nephrotoxicity of kanamycin is enhanced when administered with low molecular weight plasma expanders. Release of lysosomal enzyme (β-glucuronidase) in vitro, and release of soluble enzyme (lactic dehydrogenase) into blood stream were taken asthe indicators of tissue damage caused by administration of drugs in this study.
Five groups of female albino rats weighing 180 to 200g were treated by 1) dehydration, 2) dehydration and kanamycin (abrv. Km), 3) dehydration and low molecular weight dextran (abrv. Dxt, 50ml/kg of 10% solution), 4) dehydration, Km and Dxt, or 5) dehydration, Km, Dxt and hydrocortisone.
β-Glucuronidase study: Activity of the enzyme was measured in the supernatant fraction of tissue homogenate obtained by mechanical destruction and centrifugation, and in the medium containing the enzyme released from the lysosomal fraction during incubation at 37°C. Both experiments showed that the release of β-glucuronidase was most marked in group 4). The activity in groups 2), 3) and 5) was statistically lower than that in 1). These data indicated that the combination of Km and Dxt more labilized the kidney lysosome than the administration of either drug alone did, and that hydrocortisone partly restored the labilizing effect of these drugs.
Lactic dehydrogenase (LDH) study: 1) Serum LDH level was not increased by dehydration alone. Dxt caused a rapid and short-term rise. However, combination of Dxt and Km showed a gradual longlasting increase of serum LDH activity. Cortisone incompletely inhibited the increase. 2) Kidney fraction of LDH (absorbed on DEAE cellulose) showed about 50% of the total activity on the average 6 hours after treatment with the combination. With Dext alone, only a few per cent of the total was absorbed on DEAE cellulose, indicating that most LDH in serum was released from the liver. Cortisone did not affect the ratio of fractions greatly. 3) Electrophoretic separation of LDH isoenzymes showed that LDH-5 was dominant in the serum from animals treated with Dxt. However, in the animals treated with the combination, 5 bands (from LDH-1 to LDH-5) were visible. Cortisone did not affect the released isoenzyme pattern.