Effects of gabexate mesilate on serum inflammatory cytokines in rats with acute necrotizing pancreatitis.
Gabexate mesilate is a synthetic protease inhibitor. The effectiveness of gabexate mesilate in patients with acute pancreatitis is controversial. Proinflammatory cytokines are associated with systemic inflammatory response syndrome (SIRS) in acute pancreatitis. A compensatory anti-inflammatory response occurs in parallel with SIRS. We investigated the effects of gabexate mesilate on acute necrotizing pancreatitis in rats, emphasizing the changes in serum levels of proinflammatory and anti-inflammatory cytokines. Acute necrotizing pancreatitis was induced by retrograde infusion of sodium taurodeoxycholate into the pancreatobiliary duct in rats. The rats were divided into three groups. Group I was given gabexate mesilate 2 mg/kg/h i.v. continuously 1 h before the induction of acute pancreatitis. Group II was given gabexate mesilate the same dose immediately after the induction of acute pancreatitis. Group III was given normal saline as the controls. Serum levels of amylase, lipase, tumor necrosis factor alpha, interleukin-6, and interleukin-10, pancreatic histopathology and hemodynamics were examined at 5h after the induction of acute pancreatitis. Gabexate mesilate significantly reduced serum levels of amylase, lipase, tumor necrosis factor alpha and interleukin-6 at 5 h. Serum levels of interleukin-10 significantly increased in Group I, as compared with Groups II and III. The severity of pancreatic histopathology, the reduction of mean arterial pressure, the volume of ascites and pancreatic wet weight/body weight ratios were also significantly improved by the administration of gabexate mesilate. The beneficial effects of gabexate mesilate on acute pancreatitis may be, in part, due to the modulation of inflammatory cytokine responses.
Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, and National Yang-Ming University School of Medicine, Taipei 112, Taiwan. chencc@vghtpe.gov.tw
Chun-Chia
CC
Chen
Sun-Sang
SS
Wang
Shyh-Haw
SH
Tsay
Fa-Yauh
FY
Lee
Rei-Hwa
RH
Lu
Full-Young
FY
Chang
Shou-Dong
SD
Lee
D000681:Amylases / Q000097:blood; D000818:Animals; D016207:Cytokines / Q000097:blood*; D016670:Gabexate / Q000494:pharmacology* / Q000627:therapeutic use; D015850:Interleukin-6 / Q000097:blood; D008049:Lipase / Q000097:blood; D008297:Male; D019283:Pancreatitis, Acute Necrotizing / Q000097:blood* / Q000188:drug therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D016207:Cytokines; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016670:Gabexate; D008049:Lipase; D000681:Amylases