Circulating levels of adhesion molecules and markers of endothelial activation in acute inflammation induced by prolonged brisk exercise.

OBJECTIVES: To investigate circulating levels of adhesion molecules and markers of endothelial activation in acute inflammation induced by prolonged brisk exercise. DESIGN AND METHODS: The circulating levels of adhesion molecules E-, L- and P-selectins, intercellular and vascular adhesion molecule-1 (ICAM-1 and VCAM-1), along with those of thrombomodulin (TM), N-terminal pro-brain natriuretic peptide (NT-pro-BNP) and cardiac troponin T, were measured before, at the end of and at 48 h post-race, in athletes participating in this extreme physical stress paradigm. RESULTS: Levels of L- and P-selectins remained the same before and at the end of the "Spartathlon" race, presenting a similar decline at 48 h post-race. E-Selectin, ICAM-1 and TM reached a maximum value at the end of the race and returned to normal 48 h after the race. A similar profile was observed for VCAM-1 and NT-pro-BNP, with a tendency for a decrease at 48 h post-race, while troponin T was not detected. CONCLUSIONS: The indices of endothelial activation are strongly affected during "Spartathlon" race, suggesting that, although prolonged brisk exercise activates the endothelium, it rapidly recovers.

The effect of alcohol and gemfibrozil co-administration in Wistar rats.

INTRODUCTION: The ingestion of alcohol (Alc) as well as gemfibrozil (Gem), a fibrate drug used to treat hypertriglyceridaemia, may occur on a long-term basis in humans. Since both Alc and Gem can disturb liver function, we assessed the effects of administering Alc together with Gem in Wistar rats. MATERIALS AND METHODS: Male Wistar rats were randomized and divided into 4 groups of 10 each. They were fed (once a day) via a stomach tube with: i) 2 ml of polyethylene glycol (Peg); group Peg, ii) 2 ml of Peg + 2 ml of 25% v/v pure Alc in water; group Alc + Peg, iii) 2 ml of Gem solution in Peg (3.4 mg/100 g body weight); group Gem +Peg, iv) 2 ml of Gem solution in Peg 2 + 2 ml of Alc; group Gem +Alc +Peg. Another 13 male Wistar rats were only fed a standard laboratory diet (control group). After 8 weeks, blood samples were drawn and the livers removed. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AP), total cholesterol (TC) and triglycerides (TG) were measured. Liver histopathology was also assessed. RESULTS: All tube-fed groups had higher body mass index compared to controls (p<0.001). The control group had lower AP compared to Gem+Peg and Gem +Alc+Peg groups (p=0.005 and p=0.018, respectively). The Peg group had lower AP compared to G+Peg (p=0.041). All tube-fed groups had lower ALT compared to controls (p<0.001). The TC levels were lower in tube-fed groups with Gem (Gem +Peg and Gem+Alc +Peg) compared to controls (p=0.002 and p=0.039, respectively). Among the tube-fed groups, the TC level was lower in Gem +Peg compared to Peg and Alc+Peg groups (p=0.047 and p=0.01, respectively). No differences were found among tube-fed groups and control rats in blood AST and TG. Liver histopathology was similar in all groups and within the normal range. CONCLUSION: A moderate amount of Alc daily together with Gem is safe in rats. Peg administration in Wistar rats protects from the Alc-induced TG and AST rises.

Granulocyte-colony stimulating factor administration ameliorates liver regeneration in animal model of fulminant hepatic failure and encephalopathy.

It has previously been shown that recombinant granulocyte-colony stimulating factor (rG-CSF) accelerates and enhances hepatocyte proliferation in partially hepatectomized rats. In the present study, we examined the effect of rG-CSF administration on liver injury, regeneration, and survival outcome in an experimental rat model of fulminant hepatic failure (FHF) and encephalopathy induced by repeated injections of thioacetamide (TAA). FHF was induced in adult male Wistar rats by three consecutive intraperitoneal injections of TAA, at intervals of 24 hr. The animals were also injected with either saline or rG-CSF. Serum biochemical parameters and blood ammonia levels, liver histology, stage of hepatic encephalopathy, and survival were statistically significantly improved in TAA-intoxicated and rG-CSF-treated rats compared to TAA-intoxicated and saline-treated ones. Furthermore, rG-CSF not only ameliorated the histologically evident liver injury in a statistically significant manner but also enhanced the proliferative capacity of the hepatocytes. Our data confirm the beneficial effect of rG-CSF administration in this animal model of FHF and encephalopathy, supporting evidence for a possible use of rG-CSF as supportive therapy in the management of FHF.

Hepatic stimulator substance administration ameliorates liver regeneration in an animal model of fulminant hepatic failure and encephalopathy.

AIMS/BACKGROUND: Hepatic stimulator substance (HSS) is a liver-specific growth factor implicated in hepatocellular proliferation and hepatoprotection in models of acute liver injury. In the present study, we examined the effect of exogenous HSS administration on liver proliferating capacity and survival outcome in an experimental animal model of fulminant hepatic failure (FHF) and encephalopathy, induced by repeated injections of thioacetamide (TAA) in rats. METHODS: Fulminant hepatic failure was induced in adult male Wistar rats by three consecutive intraperitoneal injections of TAA (400 mg/kg of body weight), at 24 h time intervals. The animals received intraperitoneally either a saline solution or HSS (50 mg protein/kg of body weight), 2 h after the second and third TAA injections. The animals were killed at 6, 12 and 18 h post the last injection of TAA. RESULTS: Levels of liver enzymes and urea in serum, blood ammonia values, liver histology, stage of hepatic encephalopathy and survival were statistically significantly improved in TAA-intoxicated and HSS-treated rats compared to TAA-intoxicated and saline-treated ones. Furthermore, HSS ameliorated liver regenerative indices--DNA biosynthesis, thymidine kinase activity and hepatocyte mitotic activity--in a statistically significant manner. CONCLUSIONS: Our data suggest the beneficial effect of HSS administration in this animal model of FHF and encephalopathy, supporting evidence for a possible use of HSS as supportive therapy, by increasing hepatocellular proliferation, in management of FHF.

Hepatic stimulator substance activity in animal model of fulminant hepatic failure and encephalopathy.

Hepatic stimulator substance (HSS) is a known liver-specific but species-nonspecific growth factor. In the present study we examined the activity of the endogenously produced HSS in an established experimental model of fulminant hepatic failure (FHF) and encephalopathy, induced by repeated injections of thioacetamide (TAA). FHF was induced by three consecutive intraperitoneal injections of TAA (400 mg/kg body weight) in rats, at time intervals of 24 hr. The animals were killed at 0, 6, 12, or 18 hr following the last injection of TAA. The rate of tritiated thymidine incorporation into hepatic DNA, the enzymatic activity of liver thymidine kinase (EC 2.7.1.21), and the assessment of mitotic index in hepatocytes were used to estimate liver regeneration. HSS extract obtained from the livers of TAA-treated rats, sacrificed at the above-mentioned time points was tested for its activity. Increased HSS activity was noted in all TAA-treated animals, presenting a peak at 12 hr following the third TAA dose, suggesting active participation of this growth factor in hepatocyte replication in this animal model of FHF and encephalopathy. It may also be suggested that up-regulation of HSS activity could be used in future as a therapeutic approach in FHF.