CHLOROQUINE STABILIZES PANCREATIC LYSOSOMES AND IMPROVES SURVIVAL OF MICE WITH DIET-INDUCED ACUTE-PANCREATITIS

Activation of digestive zymogens by lysosomal enzymes has been suggest ed as a triggering event in acute pancreatitis (AP). Chloroquine (CQ), a weak base that accumulates in the lysosomes and increases their pH, can inhibit the activity of lysosomal enzymes. In the present study, we examined the effect of CQ on choline-deficient, ethionine-supplemen ted (CDE) diet-induced AP. CQ-diphosphate (15-50 mg . kg(-1)) or vehic le was given intraperitoneally at 0, 24, and 48 h to female CD1 mice t hat were fed with either normal diet or CDE diet. For mortality studie s, animals were observed for 168 h. Serum and pancreas samples were co llected from animals sacrificed 56 h after the start of the CDE diet. Treatment with CQ at 50 mg . kg(-1) significantly (p < 0.05) improved the survival of mice with CDE diet-induced AP. In the normal pancreas, CQ decreased the specific activity of lysosomal enzymes cathepsin B1, beta-hexosaminidase, beta-glucuronidase, and acid phosphatase. In the pancreas with AP, CQ did not modify the activity of cathepsin B1, whe reas it increased the latency of all enzymes. In conclusion, our resul ts confirm the beneficial effect of CQ on survival of mice with CDE di et-induced AP and suggest that this effect of CQ may be due to its sta bilizing action on lysosomes.