Deferoxamine and meropenem combination therapy in experimental acute pancreatitis.
BACKGROUND
Recent data from the experimental clinical studies suggest that antibiotics having good penetration to pancreas may reduce mortality by preventing pancreatic infection, which is the most important prognostic factor in acute pancreatitis (AP). Deferoxamine is an active free oxygen radical scavenger, which has been shown to have a protective role in development of acute pancreatitis.


OBJECTIVE
To determine the effects of combination of deferoxamine and meropenem in acute necrotizing pancreatitis.


METHODS
One hundred male Sprague-Dawley rats were randomly divided into 5 groups. All rats underwent laparotomy with cannulation of biliopancreatic duct. Group 1 received intraductal saline injection. Acute necrotizing pancreatitis was induced in group 2, 3, 4, and 5 by intraductal injection of 3% taurocholate. Group 1 (sham operated) and group 2 were injected with saline of 0.3 mL/kg intraperitoneally (i.p). Group 3 was injected with meropenem 60 mg/kg/d i.p, group 4 with deferoxamine 80 mg/kg/d s.c and group 5 with combination of these 2 agents at the same doses. While meropenem was started 2 hours later, all treatments were started immediately after the induction of pancreatitis. All rats were killed at the 48th hour of the treatment and blood and tissue samples were collected for amylase determinations, pathologic examinations, and culture.


RESULTS
There was no difference in serum amylase levels between AP induced groups (P > 0.05). Pancreatic histology scores were significantly low in rats treated with deferoxamine (group 4), and combination regimen (group 5) (P < 0.001). Meropenem significantly reduced the incidence of pancreatic infection. Although combination of deferoxamine with meropenem showed better effects than meropenem alone in terms of pancreatic infection, the difference did not reach to statistical significance.


CONCLUSIONS
Meropenem treatment reduces secondary pancreatic infections in acute pancreatitis. Treatment with deferoxamine and meropenem combination may be more beneficial than single therapies in reducing the severity of pancreatitis. Further studies investigating the effects of this combination on survival are needed.
D000208:Acute Disease; D000818:Animals; D001419:Bacteria / Q000302:isolation & purification; D001424:Bacterial Infections / Q000150:complications* / Q000188:drug therapy* / Q000382:microbiology; D002404:Catheterization; D003676:Deferoxamine / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D007813:Laparotomy; D008297:Male; D000077731:Meropenem; D019283:Pancreatitis, Acute Necrotizing / Q000150:complications* / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013845:Thienamycins / Q000008:administration & dosage / Q000627:therapeutic use*
D013845:Thienamycins; D000077731:Meropenem; D003676:Deferoxamine