Furosemide-induced lysosomal enzyme release in mouse kidney in vivo and in vitro

The loop diuretic, furosemide, which has been known to elicit renin release in vivo as well as in vitro, has also been shown to induce lysosomal enzyme release. After administration of furosemide (10 mg/kg and 300 mg/kg), a significantly increased acid phosphatase activity (1.33 x 10(-4) and 1.73 x 10(-4) vs. 0.23 x 10(-4) U, p < 0.001) was detected in the urine of the drug-treated mice, accompanied by a reduction of the residual enzyme activity in the kidney (5.0% for 10 mg/kg and 18.4%--p < 0.05--for 300 mg/kg dosage). Two marker enzymes, acid phosphatase and beta-D-glucuronidase, were assayed to demonstrate that furosemide also exerts its effect in in vitro systems like renal cortex suspension (corr. coeff.: 0.899 for acid phosphatase and 0.908 for beta-D-glucuronidase, p < 0.001) and isolated lysosomes (corr. coeff.: 0.981 for acid phosphatase and 0.989 for beta-D-glucuronidase, p < 0.001 for both). This action of the drug seems to be different from the well-known furosemide-sensitive inhibition of ion transport systems and may become of clinical relevance for patients receiving high doses of furosemide.