The aim of this study was to test the hypothesis that apoptosis can protect against experimental
pancreatitis and induction of apoptosis by an extract of Artemisia asiatica (DA-9601) is beneficial in
cerulein-induced pancreatis in rats.
Pancreatitis was induced in 6-week-old male SPF Sprague-Dawley rats by two intravenous (i.v.) administrations of 40 microg/kg
cerulein. To investigate the effects of
DA-9601 on the severity of
pancreatitis and extent of apoptosis, rats were treated with intragastric
DA-9601, 30 mg/kg (D30), 100 mg/kg (D100), or 300 mg/kg (D300), intraperitoneal
superoxide dismutase, 10,000 U/kg (SOD), and i.v.
gabexate mesilate, 40 mg/kg (
Foy), three times (30 min before
cerulein injection, 30 and 90 min after
cerulein injection). The control group was administered vehicle alone. Ten rats were included in each treatment group and control group. Rats were sacrificed 5 h after
cerulein treatment. Serum
amylase, histological activity index (HAI), pancreatic
lipid peroxide levels, and apoptotic index [in situ hybridization by
terminal deoxynucleotidyl transferase-mediated dUTP-
biotin nick end-labeling (TUNEL)] were determined. Gel electrophoresis was performed for the presence of
DNA fragmentations. The results were as follows. Serum
amylase was significantly increased in all
cerulein-treated groups compared to normal controls (p < 0.001). The HAI was significantly decreased in only the D300 group compared to the controls (p < 0.05). The apoptotic index of the
cerulein-alone group was 3.8 +/- 2.7, but the mean apoptotic indexes of the SOD and
Foy groups were 16.4 +/- 4.6 and 13.3 +/- 1.8, respectively, a significant increase (p < 0.01). The apoptotic index was more significantly increased in the DA-9601-treated groups, dose dependently (8.4 +/- 3.4 in D30, 14.8 +/- 4.3 in D100, 24.2 +/- 4.7 in D300). A smearing pattern of
DNA electrophoresis was noted in the DA-9601-treated groups. In conclusion,
DA-9601, an extract of Artemisia, induced apoptosis of pancreatic acinar cells dose dependently and concomitantly attenuated the severity of
pancreatitis.