Octreotide prevents L-asparaginase-induced pancreatic injury in rats.
OBJECTIVE
L-asparaginase (ASNase) is one of the most effective chemotherapeutic means for inducing remission in acute lymphoblastic leukemia. However, because of unknown risk factors, severe pancreatitis sometimes occurs in patients receiving ASNase. We assessed the effect of ASNase on pancreatic acinar cells and then investigated the preventive effects of octreotide against ASNase-induced pancreatic injury in rats.


METHODS
Rats received intraperitoneal injections of an Escherichia coli ASNase solution (200, 500, or 1000 IU/kg) or normal saline as a control every 24 hours for 5 days. Octreotide (3 microg/kg) was injected subcutaneously with ASNase (1000 IU/kg) every 8 hours for 5 days. Rats were sacrificed 24 hours after the last injection of ASNase or normal saline.


RESULTS
Only the rats given 1000 IU/kg ASNase had significantly increased levels of pancreatic amylase (1962 +/- 152 vs 2179 +/- 84 IU/L, p < 0.01), trypsin (27.3 +/- 3.6 vs 41.1 +/- 22.8 IU/L, p < 0.05), and pancreatic secretory trypsin inhibitor (0.03 +/- 0.09 vs 0.27 +/- 0.10 ng/mL, p < 0.01) as compared to the control group. In addition, the acinar cells showed histological damage; however, octreotide injection provided protection against histological damage and the pancreatic enzymes remained within normal limits.


CONCLUSIONS
Although ASNase by itself did not cause pancreatitis, it did cause increased levels of pancreatic enzymes and histological damage to the pancreas associated with pancreatic injury or pre-pancreatitis. Prior treatment with octreotide prevented the development of ASNase-induced pancreatic injury.
Suzuki
Mitsuyoshi
M
Department of Pediatrics, Juntendo University School of Medicine, Tokyo, Japan. f-mitsuo@zc5.so-net.ne.jp
Shimizu
Toshiaki
T
Kudo
Takahiro
T
Shoji
Hiromichi
H
Ohtsuka
Yoshikazu
Y
Yamashiro
Yuichiro
Y
D000681:Amylases / Q000097:blood; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000494:pharmacology; D001215:Asparaginase / Q000009:adverse effects* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D029968:Escherichia coli Proteins / Q000009:adverse effects / Q000494:pharmacology; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D008297:Male; D015282:Octreotide / Q000494:pharmacology*; D010179:Pancreas / Q000293:injuries / Q000473:pathology; D010195:Pancreatitis / Q000097:blood / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D014357:Trypsin / Q000097:blood; D014361:Trypsin Inhibitors / Q000097:blood
D000970:Antineoplastic Agents; D029968:Escherichia coli Proteins; D005765:Gastrointestinal Agents; D014361:Trypsin Inhibitors; D000681:Amylases; D014357:Trypsin; D001215:Asparaginase; D015282:Octreotide