The antibiotic fosfomycin protects pancreatic lysosomes in rats with caerulein-induced acute pancreatitis

The protective effect of an antibiotic, fosfomycin, on the exocrine pancreas was evaluated in rats with caerulein-induced acute pancreatitis. A supramaximal dose of caerulein (5 mu g/kg h for 4 h) caused significant hyperamy-lasaemia and marked pancreatic histological changes such as interstitial odoema and acinar cell vacuolisation. A supramaximal dose of caerulein also caused a significantly accelerated leakage of lysosomal enzyme, cathepsin B, from pancreatic lysosomes in in vitro incubation, indicating increased lysosomal fragility during acute pancreatitis. A supramaximal dose of caerulein caused a significant increase in pancreatic trypsin content. Administration of fosfomycin al a dose of 20 mg/kg h for 4 h during caerulein infusion exerted significant protective effects against the pancreatic injuries induced by a supramaximal dose of caerulein. These results indicate that pancreatic lysosomal fragility seems to play an important role in the pathogenesis of acute pancreatitis, since cathepsin B can activate trypsinogen. They also suggest a possible usefulness of fosfomycin in the treatment of acute pancreatitis.