Pepstatin, an Ascites Retardant of L1210 Tumor-Bearing Mice: Brief Communication2

Abstract

The effect of pepstatin on the kinetics of ascitic fluid accumulation in L1210 tumor-bearing mice (DBA/2) was observed. Following inoculation of 1.5x10(6) tumor cells, untreated mice reached a peak of fluid accumulation on day 6 and remained at this level until death on day 9. A "lag" phase of 4 days occurred before fluid accumulation was seen. Pepstatin administered SC in a single dose of 80 mg/kg during the lag phase, significantly retarded fluid accumulation as compared to untreated animals. Pepstatin administered following fluid accumulation was much less effective. We concluded that pepstatin prevents fluid accumulation rather than acts as a diuretic agent. The term "ascites retardant" is suggested for the pharmacologic actions of pepstatin, since it prevents fluid accumulation without diminishing the cell count.

Leukokinin-H generated from human ascites fluid; its isolation and pharmacology

“…6). Strong additional evidence for this concept comes from the finding that when an inhibitor of leukokinin generation, pepstatin, is administered parenterlly to ascites tumor-bearing mice, there is a significant and dramatic reduction in ascites fluid accumulation [9,10].…”

“…Since leukokinin generating systems have been found in murine and human ascites fluid of neoplastic etiology [7][8][9], we have implicated them as causitive mediators of increased permeability and ascites formation in neoplastic disease [5,6]. Further evidence that leukokinins may mediate ascites fluid formation comes from our observations that pepstatin, which is a potent inhibitor of the leukokinin-forming enzymes, significantly reduces murine ascites fluid accumulation when parenterally administered to ascites tumor-bearing mice [9,10]. Likewise, pepstatin prevents leukokinin formation in vitro in ascites fluids of patients with ovarian carcinoma which ordinarily generate leukokinins at acid pH [9].…”

Leukokinins; their pharmacological properties and role in the pathology of fluid (ascites) accumulation

“…Proof for this theory was seen when an inhibitor of the leukokinin generating system, pepstatin, was administered to mice inoculated with L-1210 cells and which develop peritoneal ascites. The pepstatin treatment significantly and dramatically reduces ascites accumulation, especially when given before ascites develops [15] (Fig. 2).…”