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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Takase
K
K
First Department of Surgery, Kobe University School of Medicine, Japan.
Takeyama
Y
Y
Nishikawa
J
J
Ueda
T
T
Hori
Y
Y
Yamamoto
M
M
Kuroda
Y
Y
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001201:Ascites / Q000503:physiopathology; D001562:Benzimidazoles; D001798:Blood Proteins / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology; D005122:Exudates and Transudates; D005456:Fluorescent Dyes; D020287:In Situ Nick-End Labeling; D007274:Injections, Intraperitoneal; D007684:Kidney Tubules / Q000166:cytology / Q000473:pathology*; D008297:Male; D009924:Organ Culture Techniques; D019283:Pancreatitis, Acute Necrotizing / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D014462:Ultrafiltration
D001562:Benzimidazoles; D001798:Blood Proteins; D005456:Fluorescent Dyes; D014409:Tumor Necrosis Factor-alpha; C017807:bisbenzimide ethoxide trihydrochloride