STUDIES ON NEPHROTOXICITY OF ANTIBIOTICS

Abstract

Nephrotoxicity of antibiotics was investigated to determine the order of these antibiotics according to their toxicity to the kidney. Adequate methods for evaluating renal damage were also studied.
The respiratory activity of renal tissue, the p-aminohippurate uptake by slices of the renal cortex and the activities of alkalinephosphatase, lactic dehydrogenase and leucine aminopeptidase in the organ have been employed as indicators of tissue damages. Histological changes of the renal tissue were also studied.
The following antibiotics were administered to rats by intramuscular injections daily for 5 to 7 days: Kanamycin, Dihydrostreptomycin, Aminobenzylpenicillin, Cephaloridine, Cephalothin, Chloramphenicol (500mg/kg body weight/day), Aminodeoxykanamycin (300mg/kg/day), Dimethylchlortetracycline, Oxytetracycline (200mg/kg/day), Gentamicin (50mg/kg/day), Colistin methansulfonate (15mg/kg/day), and Polymixin B (3mg/kg day). No water was given to the rats in the whole experimental periods. Liver damage caused by the administration of antibiotics was also investigated to compare with renal impairment.
Results
1. Respiratory activity of renal tissue was most remarkably decreased in rats administered with KM, GM, or SM. Modarate reduction of respiratory activity of renal tissue was obtained in rats administered with CL, AKM, PLB, DMCT, or OTC. Administration of CER, CET, ABPC, or CP to rats caused little or no decrease in renal respiratory activity. Reduction in oxygen comsumption of renal tissue was correlated with renal damage due to administration of antibiotics.
2. Decrease in alkalinephosphatase activity of the kidney seemed to be correlated with renal impairment. Alkalinephosphatase activity of the kidney was easily reduced by small change in condition of the kidney, while succinoxidase activity of the kidney was reduced following severe renal impairment.
3. L. A. P. activity of the kidney was not markedly correlated with activity of renal alkalinephosphatase. L. A. P. activity of kidneys showed small reduction in rats administered with KM, AKM, DMCT, or OTC wheras activity of renal alkalinephosphatase decreased markedly.
4. Activity of renal L. D. H. falls to slightly below the control value but there was no remarkable difference among different antibiotics.
5. In general, PAH uptake by slices of the renal cortex was correlated with respiratory activity of the kidney. Moderate reduction of respiratory activity of the kidney was observed in rats administered with CL, PLB, DMCT, or OTC while remarkable reduction of PAH uptake by slices of the renal cortex was obtained in these cases.
6. Oxygen consumption of liver tissue showed remarkable reduction in rats administered with CER or ABPC. There was no descrease in respiratory activity by other antibiotics.
7. Histological findings of the kidneys were correlated to changes of respiratory activities or to those of PAH uptake.