Effects of diazoxide in experimental acute necrotizing pancreatitis

Abstract

OBJECTIVE:We aimed to assess the effects of diazoxide on the mortality, pancreatic injury, and inflammatory response in an experimental model of acute pancreatitis.METHODS:Male Wistar rats (200–400 g) were divided randomly into two groups. Fifteen minutes before surgery, animals received physiological (0.9%) saline (3 mL/kg) (control group) or 45 mg/kg diazoxide (treatment group) via the intravenous route. Acute pancreatitis was induced by injection of 2.5% sodium taurocholate via the biliopancreatic duct. Mortality (n=38) was observed for 72 h and analyzed by the Mantel–Cox Log-rank test. To study pancreatic lesions and systemic inflammation, rats (10 from each group) were killed 3 h after acute pancreatitis induction; ascites volume was measured and blood as well as pancreases were collected. Pancreatic injury was assessed according to Schmidt’s scale. Cytokine expression in plasma was evaluated by the multiplex method.RESULTS:Mortality at 72 h was 33% in the control group and 60% in the treatment group (p=0.07). Ascites volumes and plasma levels of cytokines between groups were similar. No difference was observed in edema or infiltration of inflammatory cells in pancreatic tissues from either group. However, necrosis of acinar cells was lower in the treatment group compared to the control group (3.5 vs. 3.75, p=0.015).CONCLUSIONS:Treatment with diazoxide can reduce necrosis of acinar cells in an experimental model of acute pancreatitis, but does not affect the inflammatory response or mortality after 72 h.

Case Report: A Difficult-to-Diagnose Case of Hyperinsulinemic Hypoglycemia Surgically Treated After Developing Acute Pancreatitis

“…De Broe et al were the first to suggest acute pancreatitis as a potential adverse effect of diazoxide, and Badalov et al described diazoxide as a rare cause of acute pancreatitis (31,32). Interestingly, de Oliveira Andrade et al reported that diazoxide reduces necrosis of acinar cells in rats with acute pancreatitis, although the mortality rate was higher in the diazoxide-treated group than in the untreated group (33). Overall, these observations highlight the importance of considering diazoxide as a potential cause of drug-induced acute pancreatitis in patients receiving the drug for a long term.…”