Maria D. Demonakou

Effect of serotonin receptor 2 blockage on liver regeneration after partial hepatectomy in the rat liver.

Abstract: The effect of serotonin receptor 2 blockade (5‐HT2) on liver regeneration after 30–34% and 60–70% partial hepatectomy in the rat liver was investigated.

Soluble triggering receptor expressed on myeloid cells (sTREM-1): a new mediator involved in the pathogenesis of peptic ulcer disease.

Objectives Triggering receptor expressed on myeloid cells (TREM-1) is a promoter of cytokine production triggered by microbial components. To investigate the significance of its soluble counterpart, sTREM-1, for the pathogenesis of peptic ulcer disease, sTREM-1 was compared with the proinflammatory mediators and the pathology score of gastritis. Methods Forty patients with dyspepsia were enrolled: 20 with peptic ulcer and 20 controls without any macroscopic abnormalities. All patients were examined by endoscopy; gastric juice was aspirated and biopsy specimens were collected from the antrum and corpus of the stomach. sTREM-1 was estimated by a hand-made enzyme immunoassay. Interleukin-8 was estimated by enzyme-linked immunosorbent assay and lipid peroxidation, indexed by malondialdehyde, by the thiobarbituric assay, after passage through a high-performance liquid chromatography system. Results The median (±SE) of sTREM-1 of controls and patients with ulcer was 3.91±0.57 and 44.27±241.55 RU, respectively (P=0.006). The median (±SE) of interleukin-8 of controls and patients with ulcer was 1802.97±122.10 and 2030.66±64.44 pg/ml, respectively (P=0.023). sTREM-1 was positively correlated with the density of neutrophil and mononuclear infiltration scores and the total Sydney score (P=0.029, 0.043 and 0.041, respectively). sTREM-1 was positively correlated with interleukin-8 (P=0.042). Conclusions sTREM-1 might be an independent factor involving with the peptic ulcerative inflammatory process that is positively correlated with histopathological abnormalities of gastritis.

Effect of Hepatic Stimulator Substance (HSS) on Cadmium-Induced Acute Hepatotoxicity in the Rat Liver

The hepatoprotective effect of HSS against cadmium-induced liver injury was investigated. Ratswere intoxicated with a dose of cadmium (3.5 mg/kg b.w.). The rats were treated with normalsaline (group I) or HSS (100 mg protein/kg b.w.; group II) 2 hr later and killed at different timepoints. Hematoxylin-eosin (HE) sections were assessed for necrosis, apoptosis, peliosis, mitoses,and inflammatory infiltration. Serum enzyme activities were assayed. Apoptosis was quantified by theTunel technique. Thymidine kinase activity and the rate of [ 3 H]thymidine incorporation into DNAwere also assayed. Necrosis, hepatocyte apoptosis, and peliosis were minimized in HSS-treatedrats (group II). Nonparenchymal cell apoptosis and liver regeneration were not quantitively alteredin the HSS-treated group, though the time profile was different. HSS protects hepatocytes againstcadmium-induced necrosis, apoptosis, and peliosis. Apoptosis was the major type of cell death fornonparenchymal liver cells and strongly correlated with the extent of peliosis. Interactions betweenhepatocytes and nonparenchymal liver cells seem to be important for the genesis of hepatic traumain acute cadmium hepatotoxicity.

Gadolinium chloride pretreatment ameliorates acute cadmium-induced hepatotoxicity.

Cadmium is a known industrial and environmental pollutant. It causes hepatotoxicity upon acute administration. Features of cadmium-induced acute hepatoxicity encompass necrosis, apoptosis, peliosis and inflammatory infiltration. Gadolinium chloride (GdCl3) may prevent cadmium-induced hepatotoxicity by suppressing Kupffer cells. The effect of GdCl3 pretreatment on a model of acute cadmium-induced liver injury was investigated. Male Wistar rats 4–5 months old were injected intraperitoneally with normal saline followed by cadmium chloride (CdCl2; 6.5 mg/kg) or GdCl3 (10 mg/kg) followed by CdCl2 (6.5 mg/kg; groups I and II, respectively). Rats of both the groups were killed at 9, 12, 16, 24, 48 and 60 h after cadmium intoxication. Liver sections were analyzed for necrosis, apoptosis, peliosis and mitoses. Liver regeneration was also evaluated by tritiated thymidine incorporation into hepatic DNA. Serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were also determined. Hepatic necrosis, hepatocyte and nonparenchymal cell apoptosis and macroscopic and microscopic types of peliosis hepatis were minimized by gadolinium pretreatment. Serum levels of AST and ALT were also greatly diminished in rats of group II. Tritiated thymidine incorporation into hepatic DNA was increased in gadolinium pretreatment rats. Kupffer cell activation was minimal in both the groups of rats. Gadolinium pretreatment attenuates acute cadmium-induced liver injury in young Wistar rats, with mechanisms other than Kupffer cell elimination.

The Hepatoprotective Effect of Hepatic Stimulator Substance (HSS) Against Liver Regeneration Arrest Induced by Acute Ethanol Intoxication

Male Wistar rats were randomized to receive ethanol (2.5 ml/kg by gastric intubation every 8 hr; group I), equal volumes of isocaloric to ethanol sucrose solution (group II), or ethanol and HSS (100 mg/kg intraperitoneally 10 and 16 hr after partial hepatectomy; groups III and IV, respectively) for up to 96 hr after partial hepatectomy, with ethanol administration starting 1 hr prior to partial hepatectomy. Animals were killed at 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60, and 96 hr after partial hepatectomy. The rate of liver regeneration was evaluated by the mitotic index in H&E-stained sections, immunochemical detection of Ki67 nuclear antigen, rate of [3H]thymidine incorporation into hepatic DNA, and liver thymidine kinase enzymatic activity. The biological activity of HSS in groups I and II rats was evaluated using a bioassay. Ethanol administration arrested liver regeneration during the first 32 hr after partial hepatectomy and suppressed HSS activity throughout the period examined. Liver regeneration progressed after 32 hr despite the low levels of HSS activity. HSS administration at 10 and 16 hr reversed liver regeneration arrest induced by ethanol. Acute ethanol administration induces cell cycle arrest during the first 32 hr after partial hepatectomy and suppression of HSS biological activity seems to contribute to this effect. HSS administration reversed the inhibitory effect of ethanol on liver regeneration and caused synchronized entrance of hepatocytes in the S phase of the cell cycle. HSS seems to participate in the network of growth factors controlling the G1/S cell cycle checkpoint.