Asaeda N, Shinoda M, Tamano S, Ikawa E, Yoshiyasu T, Iwai H, Nagai N, Tagawa Y, Koide M
J Toxicol Sci. 1984 Jun;9 Suppl 1:73-88. doi: 10.2131/jts.9.supplementi_73.
This study was performed to compare the acute-renal toxicity of azosemide (SK-110) or furosemide (FM) treatment in combination with cephaloridine (CER). 1) Initially, the acute-renal toxicity of CER was studied after a subcutaneous administration at dose levels of 500, 1000, 1500 and 2000 mg/kg. The values of BUN, creatinine and relative kidney weights were increased in rats given CER at dose levels above 1500 mg/kg. consequently, it was considered that the threshold of CER with regard to acute-renal toxicity was 1000 mg/kg. 2) Secondarily, the acute-renal toxicity of SK-110 or FM were studied after oral administration of 40, 80, 160 or 320 mg/kg doses alone or in combination with CER. Acute-renal toxicity was evident in the 320 mg/kg-treated rats after both SK-110 and FM alone, as revealed by analysis of a number of parameters, i.e., BUN, serum creatinine, urine sediment and composition and pathological data composing both kidney weights and studies at the microscope level. However, the increase of BUN and relative kidney weights values, elevated numbers of epithelial cells in the urine and necrosis observed in the uriniferous-tubular epithelium on histopathological examination of kidneys were noted in rats given at dose levels of only 80 mg/kg with SK-110 + CER, whereas they were seen in animals treated with FM even at the lowest applied dose of 40 mg/kg in combination with CER. In conclusion, this study showed that the minimum dose of SK-110 or FM in combination with CER which causes acute-renal toxicity were, respectively, 80 mg/kg or less than 40 mg/kg.