Protective effects of leflunomide on intestinal ischemia-reperfusion injury: leflunomide against intestinal ischemia-reperfusion.

AIM: The aim of this study was to investigate the possible protective effects of leflunomide, which has antioxidant and anti-inflammatory properties, against intestinal IR injury in rats. MATERIALS AND METHODS: Forty female Wistar albino rats were divided into six groups: control (n = 5), drug control (n = 7), sham operated (n = 7), IR alone (n = 7), IR plus vehicle (IR + vehicle, n = 7) and IR plus 20 mg/kg leflunomide (IR + Leflunomide, n = 7). While rats were pretreated intragastrically with leflunomide (20 mg/kg) and vehicle in three doses prior to the experiment, respectively, in the IR + Leflunomide and IR + vehicle groups, no additional application was done in the IR alone group. Intestines were exteriorized, and the superior mesenteric artery was occluded for 45 min ischemia, and then the clamp was removed for 120 min reperfusion. After the experiment, the intestines were removed for biochemical and histological examinations. Additionally, blood samples were taken for measurements of antioxidant parameters. RESULTS: The intestinal IR significantly increased the MDA level and MPO activity; however, treatment with leflunomide reversed those findings (P < 0.05). The CAT activity of the IR + Leflunomide group was significantly higher than in the IR groups (P < 0.05). The SOD activity was increased in the intestinal IR group, and leflunomide treatment reversed that, too (P <0.05). The light microscopic findings showed that IR caused mucosal necrosis and leflunomide treatment reduced the morphological alterations associated with IR (P < 0.05). CONCLUSION: Intestinal IR injury may be reversed by the anti-inflammatory and antioxidant actions of leflunomide.

[Investigation of the relationship between serum nitric oxide levels, HBV-DNA and ALT levels in chronic hepatitis B patients]. / Kronik hepatit B hastalarinda serum nitrik oksit düzeyi ile HBV-DNA ve ALT düzeyleri arasindaki iliskinin arastirilmasi.

It has been reported that increased nitric oxide (NO) production by the hepatocytes during chronic inflammatory processes, plays an important role in the pathogenesis of chronic hepatitis B. The aim of this study was to investigate the relationship between serum levels of NOx (nitrite + nitrate) with the viral load and alanine aminotransferase (ALT) levels in chronic hepatitis B (CHB) patients. A total of 93 CHB patients (67 male, 26 female; mean age: 47.3 +/- 10.9 years) and 53 healthy control subjects (17 male, 36 female; mean age: 58.6 +/- 2.1 years) followed-up during 2006-2007 period were included to the study. Hepatitis B virus (HBV) serologic markers, viral load and ALT levels were studied by chemiluminescence method (Ortho-Clinical Diagnostics, USA), by real-time polimerase chain reaction (PCR) (ABI PRISM 7700, Applied Biosystem, CA), and by Aeroset System (Abbott Laboratories, USA), respectively. NOx levels were determined by a method which was based on the reduction of nitrate to nitrite by cadmium. Mean levels of ALT and HBV-DNA of the patients were found as 98.7 +/- 138.4 IU/I and 1.6 x 10(9) +/- 4.0 x 10(9) copies/ml, respectively. In the evaluation of mean levels of NOx in patient and control groups, the difference was found statistically significant (30.6 +/- 21.7 micromol/l and 23.7 +/- 5.2 micromol/l, respectively; p< 0.05). In view of the relationship between the parameters, a positive correlation was detected between viral load and ALT levels (r= 0.768; p< 0.001), besides the significant correlations between NOx and viral load, and NOx and ALT (r= 0.346, p= 0.001 and r= 0.314, p= 0.002, respectively). As a result, although the NOx levels in chronic hepatitis patients were found higher than those in the control group, and significant correlations were detected between NO, viral load and ALT, the exact role of NO in the disease pathogenesis and outcome needs to be studied further at cellular level.

Protective effects of caffeic acid phenethyl ester on intestinal ischemia-reperfusion injury.

AIM: Intestinal ischemia reperfusion (IR) causes tissue injury in two ways, starting a pro-inflammatory cascade and oxidative stress. The aim of this study was to investigate the possible protective effects of caffeic acid phenethyl ester (CAPE), which has antioxidant and anti-inflammatory properties, against intestinal IR injury in rats. MATERIALS AND METHODS: Forty male Wistar-Albino rats were divided into five groups: Sham, IR, IR plus ethanol (vehicle), IR plus 10 mg/kg (IR + 10CAPE), and 30 mg/kg CAPE (IR + 30CAPE) at the 30-min ischemic period. Intestines were exteriorized and the superior mesenteric artery was occluded for 45-min ischemia and then the clamp was removed for 120-min reperfusion. After the experiment, the intestines were removed for biochemical and light microscopic examinations. Additionally, blood samples were taken for plasma TNF-alpha measurement. RESULTS: The TBARS levels of the IR and IR + Ethanol groups were higher than the Sham group (P < 0.05). Both CAPE treatments decreased TBARS levels in comparison with the IR group (P < 0.05). In both CAPE-treated groups, while the superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were increased compared to all other groups, which was similarly the case for the CAT activity compared to the Sham and IR + Ethanol groups (P < 0.05). There were no significant differences between GSH levels of all study groups. The TNF-alpha levels of the IR and IR + Ethanol groups were non-significantly increased compared to the Sham group (P > 0.05). The TNF-alpha levels of 10 and 30 mg/kg CAPE groups were non-significantly decreased compared to the IR group (P > 0.05). The tissue MPO activities of the IR and IR + Ethanol groups were higher than the Sham group (P < 0.05). The MPO activities of the IR + 10CAPE and IR + 30CAPE groups were not significantly different from the Sham group (P > 0.05). There was necrosis of mucosa in the IR and IR + Ethanol groups in light microscopic evaluations. Those changes were significantly reversed by 30 mg/kg CAPE treatment. CONCLUSION: The intestinal IR injury may be reversed by anti-inflammatory and antioxidant actions of the CAPE. However, 30 mg/kg CAPE treatment may be more efficient in preventing intestinal IR injury in rats.

Effects of a membrane-permeable radical scavenger, Tempol, on healing of colonic anastomoses in the cecal ligation and puncture model of polymicrobial sepsis in rats.

BACKGROUND: Tempol (Sigma-Aldrich, Steinheim, Germany) is a stable piperidine nitroxide of low molecular weight that permeates biologic membranes and scavenges superoxide anions in vitro. In recent animal studies, the delaying effect of intraperitoneal sepsis on the healing of colonic anastomoses has been shown. In this study we aimed to investigate the effects of Tempol on the healing of colonic anastomoses in the presence of polymicrobial sepsis. METHODS: Anastomosis of the left colon was performed on the day after cecal ligation and puncture (CLP) in 30 rats that were divided into 3 groups: sham-operated control (laparotomy and cecal mobilization, group I, n = 10), CLP (group II, n = 10), Tempol-treated group (30 mg/kg intravenously before the construction of colonic anastomosis, group III, n = 10). On postoperative day 6, all animals were killed and anastomotic bursting pressures were measured in vivo. Tissue samples were obtained for further investigation of anastomotic hydroxyproline (HP) contents, perianastomotic myeloperoxidase (MPO) activity, malondialdehyde (MDA), and glutathione (GSH) levels. RESULTS: There was a statistically significant increase in MPO activity and MDA levels in the CLP group (group II), along with a decrease in GSH levels, anastomotic HP contents, and bursting pressure values when compared with controls (group I). However, Tempol treatment led to a statistically significant increase in anastomotic bursting pressure values, tissue HP contents, and GSH levels, along with a decrease in MPO activity and MDA levels in group III (P < .05). CONCLUSIONS: This study showed that Tempol treatment significantly prevented the delaying effect of CLP-induced polymicrobial sepsis on anastomotic healing in the left colon. Further clinical studies are needed to clarify whether Tempol may be a useful therapeutic agent to increase the safety of the anastomosis during particular surgeries in which sepsis-induced organ injury occurs.