Protective potential of montelukast against hepatic ischemia/reperfusion injury in rats.

Ischemia and reperfusion (I/R) injury is characterized by significant oxidative stress, characteristic changes in the antioxidant system and organ injury leading to significant morbidity and mortality. This study was designed to assess the possible protective effect of montelukast, a selective antagonist of cysteinyl leukotriene receptor 1 (CysLT1), on hepatic I/R injury in rats. Wistar albino rats through clamping hepatic artery, portal vein, and bile duct, were subjected to 45 min of hepatic ischemia followed by 60 min reperfusion period. Montelukast (10 mg/kg; i.p.) was administered 15 min prior to ischemia and immediately before reperfusion period. At the end of the reperfusion period, the rats were killed by decapitation. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) activity, and proinflammatory cytokines (TNF-alpha and IL-1beta) were determined 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 chemiluminescence (CL) technique with luminol and lucigenin probes. Tissues were also analyzed histologically. Serum ALT, AST, and LDH activities were elevated in the I/R group, while this increase was significantly decreased by montelukast treatment. Hepatic GSH levels and Na+, K+-ATPase activity, significantly depressed by I/R, were elevated back to control levels in montelukast-treated I/R group. Furthermore, increases in tissue luminol and lucigenin CL, MDA levels, and MPO activity due to I/R injury were reduced back to control levels with montelukast treatment. Since montelukast administration alleviated the I/R-induced liver injury and improved the hepatic structure and function, it seems likely that montelukast with its anti-inflammatory and antioxidant properties may be of potential therapeutic value in protecting the liver against oxidative injury due to ischemia-reperfusion.

Ozkan E ，Yardimci S ，Dulundu E ，Topaloğlu U ，Sehirli O ，Ercan F ，Velioğlu-Oğünç A ，Sener G ... -  《-》

Alpha-lipoic acid protects against hepatic ischemia-reperfusion injury in rats.

To evaluate the protective effect of alpha-lipoic acid in reducing oxidative damage after severe hepatic ischemia/reperfusion (IR) injury. Wistar albino rats were subjected to 45 min of hepatic ischemia, followed by 60 min reperfusion period. Lipoic acid (100 mg/kg i.p.) was administered 15 min prior to ischemia and immediately before reperfusion period. At the end of the reperfusion period aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) activity, and cytokine, TNF-alpha and IL-1beta levels were determined in serum samples. Malondialdehyde (MDA), and glutathione (GSH) levels and myeloperoxidase (MPO) activity were determined in the liver tissue samples while formation of reactive oxygen species was monitored by using chemiluminescence (CL) technique with luminol and lucigenin probes. Tissues were also analyzed histologically. Serum ALT, AST, and LDH activities and TNF-alpha and IL-1beta levels were elevated in the I/R group, while this increase was significantly lower in the group of animals treated concomitantly with lipoic acid. Hepatic GSH levels, significantly depressed by I/R, were elevated back to control levels in lipoic acid-treated I/R group. Furthermore, increases in tissue luminol and lucigenin CL, MDA levels and MPO activity due to I/R injury were reduced back to control levels with lipoic acid treatment. Since lipoic acid administration alleviated the I/R-induced liver injury and improved the hepatic structure and function, it seems likely that lipoic acid with its antioxidant and oxidant-scavenging properties may be of potential therapeutic value in protecting the liver against oxidative injury due to ischemia-reperfusion.

Dulundu E ，Ozel Y ，Topaloglu U ，Sehirli O ，Ercan F ，Gedik N ，Sener G ... -  《PHARMACOLOGY》

Amelioration of sepsis-induced hepatic and ileal injury in rats by the leukotriene receptor blocker montelukast.

Sener G ，Sehirli O ，Cetinel S ，Ercan F ，Yüksel M ，Gedik N ，Yeğen BC ... -  《PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS》

Aqueous garlic extract alleviates ischaemia-reperfusion-induced oxidative hepatic injury in rats.

Sener G ，Sehirli O ，Ipçi Y ，Ercan F ，Sirvanci S ，Gedik N ，Yeğen BC ... -  《JOURNAL OF PHARMACY AND PHARMACOLOGY》

Montelukast protects against renal ischemia/reperfusion injury in rats.

Sener G ，Sehirli O ，Velioğlu-Oğünç A ，Cetinel S ，Gedik N ，Caner M ，Sakarcan A ，Yeğen BC ... -  《PHARMACOLOGICAL RESEARCH》