Michael G. Mykoniatis

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.

The emerging role of serotonin in liver regeneration

Serotonin has a multifunctional role in many different organs serving either as a neurotransmitter in the central nervous system or a paracrine factor in the gastrointestinal tract. Over 90% of serotonin is synthesised in the enterochromaffin cells of the intestine and subsequently taken up by platelets. The involvement of platelet-derived serotonin in liver mass restoration after partial hepatectomy or toxic injury has been greatly investigated during the last decade. There is a growing body of evidence implicating serotonin in hepatic regeneration through altered expression of serotonin receptor subtypes in the liver. This review article provides a brief overview on the current knowledge about the actions of serotonin in liver regeneration.

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.

Levels of hepatic stimulator substance in liver regenerating process of partially hepatectomized rats pretreated with a single dose of carbon tetrachloride.

Liver regeneration after injury with carbontetrachloride (CCl4) followed by partialhepatectomy is a complex model involving toxicological,inflammatory, and necrotic processes. In the presentstudy, the time-course of hepatic regenerative process wasinvestigated in relation to hepatic stimulator substance(HSS) activity, administration of a single dose ofCCl4 and partial (70%) hepatectomy in malerats. To evaluate liver injury events, the levels ofserum aspartic aminotransferase (AST), alanineaminotransferase (ALT), and alkaline phosphatase (ALP)were measured. Hepatic DNA synthesis reached a maximum at 36 hr after hepatectomy in contrast to thereported 24-hr and 32-hr peaks observed in nontreatedhepatectomized rats. On the other hand, HSS activityappeared to peak at 28, 40, and 44 hr after hepatectomy in CCl4-treated rats, and it wasquite a lot lower at 24, 32, 36, 48, and 60 hr. Thehypothesis that HSS promotes liver regeneration but itdoes not initiate it, as other factors have been foundto do, is discussed.

Effect of Interferon-α2b administration on rat liver regeneration after partial hepatectomy

The purpose of the present study was todelineate the effect of interferon-α2b(IFN-α2b) administration on the liverregenerative capacity after partial hepatectomy in rats.The administration of IFN-α2bsimultaneously with partial hepatectomy did not affect hepatic2b proliferation in a statistically significant manner.When IFN-α2b was administered either 2or 12 hr postoperatively, an inhibition of hepatocyteproliferation was observed 24 hr postoperatively, while atfurther time intervals up to 48 hr, DNA synthesisremained similar to that observed in the simplypartially hepatectomized rats. The enzyme thymidinekinase (TK), has been implicated in the suppression ofproliferation in interferon-treated cell cultures. Inall IFN-α2b-treated groups of rats,alterations of TK activity were observed without beingcorrelated to the liver regenerative status. Additionally,the administration of the polyamine putrescine inpartially hepatectomized rats treated at the time ofsurgery with IFN strongly enhanced TK activity, but did not affect DNA biosynthesis. In theabove-mentioned in vivo model of controlled cellularproliferation, the administration ofIFN-α2b affected the rate of hepatocyteproliferation depending on the time of its administration; this effect was notcorrelated to the enzymatic activity of TK, as inhibitedTK activity is responsible for the suppressed DNAsynthesis in in vitro systems.

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.

Using higher‐order crossings to distinguish liver regeneration indices in hepatectomized diabetic and non‐diabetic rats

Background and Aims:  Diabetes mellitus is implicated in several liver diseases; hence, its potential affection to liver regenerative capacity is an open research question. So far, only sporadic studies have addressed this issue, mainly using basic statistical techniques. The current study evaluated the ability of a novel technique, namely higher‐order crossings (HOC), based on liver DNA biosynthesis and thymidine kinase (TK) enzymatic activity data, to discriminate liver regeneration processes between hepatectomized diabetic and non‐diabetic rats.

Immobilization of native and denatured DNA on Sephadex G200

An efficient method for the immobilization of DNA on Sephadex G200 in the presence of water soluble carbodiimide is described and investigated in this paper. An increase in the extent of binding was observed when the incubation temperature of the DNA-Sephadex mixture was changed. It was found that native DNA immobilized to Sephadex with higher efficiency than denatured DNA. However, the stability of native DNA-Sephadex complex was about the same as that of denatured DNA-Sephadex. The size of DNA released by DNA-Sephadex after incubation of a suspension of the complex was the same as that of the DNA used for immobilization. The binding mechanism of DNA to Sephadex is discussed.

Influence of two preparations of bovine albumin on the total bilirubin as determined by Thomson's method in its reference solution.

The influence of bovine albumin on the determined total bilirubin was examined by estimation of bilirubin in standard solutions prepared with albumin solutions of five different concentrations. The determinations were made by six different methods. The results show that when bilirubin was determined by Thompsons method the estimated bilirubin decreases by increasing the concentration of albumin. This discrepancy appears in preparations from two different industrial sources of albumin.