Therapeutic effect of montelukast in hepatic ischemia-reperfusion injury in rats

ABSTRACT

Hepatic ischemia-reperfusion injury (IRI) occurs in a number of clinical conditions such as trauma, hypovolemic shock, hepatic resection, and liver transplantation. Although several drugs are effective in attenuating hepatic ischemia-reperfusion (I/R) injury, there are still no satisfying treatment strategies available to prevent hepatic I/R injury. Sixty rats were randomly assigned to 3 groups: control group, I/R model group, and I/R + M group (7 mg/kg montelukast pretreatment). The total hepatic ischemia was induced for 45 minutes by clamping the hepatic artery, portal vein, and bile duct using a vascular clamp. The rats were then allowed reperfusion at 1, 3, 6 and 12 hours. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) activity, and proinflammatory cytokines (i.e., tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-1ß)) were measured in blood samples. Malondialdehyde (MDA), and glutathione (GSH) levels and myeloperoxidase (MPO) and Na+, K+-ATPase activities were determined in the liver tissue samples while formation of reactive oxygen species was monitored by using the chemiluminescence (CL) technique with luminol and lucigenin probes. Tissues were also analyzed histologically. Hepatic IRI induced a marked increase in CysLTR1, Caspase-8 and Caspase-9 protein expression in the liver, which were markedly reduced by preconditioning with a 7 mg/kg montelukast. Preconditioning with 7 mg/kg montelukast significantly attenuated liver tissue injury and liver damage and decreased plasma AST, ALT, LDH, TNF-alpha, IL-1ß, MDA and MPO levels after a hepatic IRI. In conclusion, preconditioning with montelukast could attenuate hepatic IRI and the subsequent systemic inflammatory response in rats

RESUMEN

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