Apoptotic cell death of renal tubules in experimental severe acute pancreatitis.

Abstract

Recently renal cell apoptosis has been reported in various disorders that result in renal failure. Thus we hypothesized that renal cell injury resulting from apoptosis is involved in renal failure with severe acute pancreatitis. Renal cell apoptosis in kidneys harvested from rats with necrotizing pancreatitis was evaluated by in situ nick-end labeling. Ascitic fluid that had been collected 6 hours after development of pancreatitis was injected into the peritoneal cavities of healthy rats, and renal apoptosis was also evaluated. The apoptosis-inducing activity of the ascitic fluid was estimated in vitro with use of isolated rat renal tubules and the normal rat kidney cell line NRK52E by nuclear staining, cell cycle analysis, and DNA electrophoresis. Apoptosis was detected by in situ nick-end labeling on the renal tubules 6 hours after induction of pancreatitis in vivo. Similar tubular apoptosis was detected in the rats that had intraperitoneal injection of the ascitic fluid. In in vitro analyses the ascitic fluid induced nuclear and DNA fragmentation on the isolated renal tubules and promoted apoptosis on NRK52E cells in a time-dependent manner. Apoptotic cell death of renal tubules occurs in severe acute pancreatitis within several hours and is possibly involved in the mechanism of renal failure through undefined substance(s) in the ascitic fluid associated with pancreatitis.