Reversible impairment of hepatobiliary function induced by streptozotocin in the rat

The effect of streptozotocin (SZ) on hepatobiliary function was studied in rats on the 1st, 7th and 15th days of treatment. Serum glucose increased significantly on the 1st day, and then remained high. Bile flow, bile acids output and BSP biliary excretion were significantly decreased on the 1st day of treatment, whereas serum sorbitol dehydrogenase was increased. All the parameters tested apart from serum glucose tended to normalize with time. The results suggested a transient toxic effect of SZ on the hepatocyte.     

Reversible impairment of hepatobiliary function induced by streptozotocin in the rat

Summary The effect of streptozotocin (SZ) on hepatobiliary function was studied in rats on the 1st, 7th and 15th days of treatment. Serum glucose increased significantly on the 1st day, and then remained high. Bile flow, bile acids output and BSP biliary excretion were significantly decreased on the 1st day of treatment, whereas serum sorbitol dehydrogenase was increased. All the parameters tested apart from serum glucose tended to normalize with time. The results suggested a transient toxic effect of SZ on the hepatocyte.Acknowledgment. This study was supported by a Research Grant from Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), República Argentina. Joaquín V. Rodriguez is gratefully acknowledged for doing the chromatographic analyses of sulfobromophthalein, José M. Pellegrino for performing bile acids determination, and Mr. Raúl A. Trbojevich for surgical assistance.     

Isolation,characterization, and determination of human liver (copper/zinc) metallothionein

Summary A copper-containing protein was purified from the liver of a patient with primary biliary cirrhosis by a combination of gel filtration and anion exchange chromatography. This copper-protein had UV absorption and emission spectra, an amino acid composition, and a molecular mass which were characteristic for metallothionein (MT).From 8 livers (3 control, 1 fetal and 4 primary biliary cirrhosis) MT was extracted with non-reducing buffer and centrifuged, and the pellets were re-extracted with a 1% 2-mercaptoethanol-containing buffer. The non-reducing buffer extracted a predominantly copper-containing MT from the livers of patients with primary biliary cirrhosis and a predominantly zinc-containing MT from control lives and the fetal liver. Only from the fetal liver was a copper/zinc containing MT solubilized during the re-extraction with 2-mercaptoethanol-containing buffer. These results indicate that human MT is a unique metalloprotein with age and disease-dependent characteristics.     

Isolation, characterization, and determination of human liver (copper/zinc) metallothionein

A copper-containing protein was purified from the liver of a patient with primary biliary cirrhosis by a combination of gel filtration and anion exchange chromatography. This copper-protein had UV absorption and emission spectra, an amino acid composition, and a molecular mass which were characteristic for metallothionein (MT). From 8 livers (3 control, 1 fetal and 4 primary biliary cirrhosis) MT was extracted with non-reducing buffer and centrifuged, and pellets were re-extracted with a 1% 2-mercaptoethanol-containing buffer. The non-reducing buffer extracted a predominantly copper-containing MT from the livers of patients with primary biliary cirrhosis and a predominantly zinc-containing MT from control livers and the fetal liver. Only from the fetal liver was a copper/zinc containing MT solubilized during the re-extraction with 2-mercaptoethanol-containing buffer. These results indicate that human MT is a unique metalloprotein with age and disease-dependent characteristics.     

Effects of dosage and cadmium pretreatment on the binding of cadmium in rat bile.

The effects of dosage and of cadmium pretreatment on the binding of cadmium in rat bile were studied. With increasing dose a higher cumulative biliary excretion of Cd was observed and a higher percentage of the Cd was excreted in a low-molecular-weight form. On the other hand, after cadmium pretreatment, a decrease in the cumulative biliary excretion of cadmium was observed but a greater percentage of that excreted into the bile was bound to high molecular weight compounds.     

Effects of dosage and cadmium pretreatment on the binding of cadmium in rat bile

Summary The effects of dosage and of cadmium pretreatment on the binding of cadmium in rat bile were studied. With increasing dose a higher cumulative biliary excretion of Cd was observed and a higher percentage of the Cd was excreted in a low-molecular-weight form. On the other hand, after cadmium pretreatment, a decrease in the cumulative biliary excretion of cadmium was observed but a greater percentage of that excreted into the bile was bound to high molecular weight compounds.     

The biliary excretion of [3H] lysergic acid diethylamide in Wistar and gunn rats

Summary The biliary excretion of [³H] LSD was studied in Wistar and homozygous Gunn rats. In Wistar rats approximately 46% of the given dose was recovered from bile in 2.5 h whilst in the homozygous Gunn rat 26% was recovered in the same time period. In both strains the main metabolites were glucuronides.     

Purification of acidic Z protein from human liver

Summary Preparation of Z protein from human liver is described. Z protein consists of 2 forms which have different isoelectric points, pI 5.8 and pI 8.7, respectively. The acidic Z protein has a molecular weight of about 11,000 and has binding affinity for BSP using gel filtration.     

The biliary excretion of [3H] lysergic acid diethylamide in Wistar and Gunn rats.

The biliary excretion of [3H] LSD was studied in Wistar and homozygous Gunn rats. In Wistar rats approximately 46% of the given dose was recovered from bile in 2.5 h whilst in the homozygous Gunn rat 26% was recovered in the same time period. In both strains the main metabolites were glucuronides.     

Alfalfa seeds: Effects on cholesterol metabolism

Summary Plasma cholesterol concentrations were reduced in 3 human volunteers during ingestion of diets containing alfalfa seeds (AS) for 3 weeks. No signs of toxicity were detected through serum determinations of multiple parameters. The ingestion of AS in rats decreased the concentration of plasma cholesterol, reduced intestinal absorption of exogenous and endogenous cholesterol, and increased fecal biliary excretion.The work described in this article, Publication No. 1082 of the Oregon Regional Primate Research Center, was supported with grants RR-00163 and HL-16587 from the National Institutes of Health.     

ABCB4 missense mutations D243A,K435T,G535D,I490T,R545C,and S978P significantly impair the lipid floppase and likely predispose to secondary pathologies in the human population

Bile salts are natural detergents required to solubilise dietary fat and lipid soluble vitamins. They are synthesised in hepatocytes and secreted into the luminal space of the biliary tree by the bile salt export pump (BSEP), an ATP-binding cassette (ABC) transporter in the canalicular membrane. BSEP deficiency causes cytotoxic accumulation of bile salts in the hepatocyte that results in mild-to-severe forms of cholestasis. The resulting inflammation can also progress to hepatocellular cancer via a novel mechanism involving upregulation of proliferative signalling pathways. A second ABC transporter of the canalicular membrane is also critical for bile formation. ABCB4 flops phosphatidylcholine into the outer leaflet of the membrane to be extracted by bile salts in the canalicular space. These mixed micelles reduce the detergent action of the bile salts and protect the biliary tree from their cytotoxic activity. ABCB4 deficiency also causes cholestasis, and might be expected to cause cholangitis and predispose to liver cancer. Non-synonymous SNPs in ABCB4 have now been described in patients with liver cancer or with inflammatory liver diseases that are known to predispose to cancer, but data showing that the SNPs are sufficiently deleterious to be an etiological factor are lacking. Here, we report the first characterisation at the protein level of six ABCB4 variants (D243A, K435T, G535D, I490T, R545C, and S978P) previously found in patients with inflammatory liver diseases or liver cancer. All significantly impair the transporter with a range of phenotypes exhibited, including low abundance, intracellular retention, and reduced floppase activity, suggesting that ABCB4 deficiency is the root cause of the pathology in these cases.     

Effect of taurine administration on liver lipids in guinea pig

The oral administration of 0.4% taurine in drinking water for 14 consecutive days showed the following hepatic effects in male guinea pig. The percentage of tauro-conjugated biliary bile acids was increased from 17.2-54.2%; the ratio liver weight/body weight was increased, and fatty change was induced. Liver triglyceride concentration was accordingly increased; diglyceride and phosphatidylcholine concentrations were reduced by the treatment, while phosphatidylethanolamine level was not affected. These changes suggest an adverse effect of taurine administration on phosphatidylcholine hepatic synthesis.     

Copper metabolism in the LEC rat: Involvement of induction of metallothionein and disposition of zinc and iron

The Cu concentration was about 40 times higher in the liver of LEC (Long-Evans with a cinnamon-like coat color) rats aged 77 days (227.5±21.6 g/g liver) than in Fischer rats (5.2±0.1 g/g liver). However, in the kidney and brain of the LEC rats, Cu concentrations were lower than in these organs of the Fischer rats. Cu concentration in the hepatic metallothionein fraction was about 130 times higher in the LEC rats than in the Fischer rats. The LEC rats showed markedly low concentrations of Cu in the serum and bile. It seems likely that excretion of Cu from the liver into the bile and blood (as ceruloplasmin) is inherently lacking in the LEC rat.     

Effects of probenecid on plasma/tissue distribution of14C-benzylpenicillin in rats

Summary Probenecid (50 mg·kg^–1) was found to induce an increase of the plasma concentration of¹⁴C-benzylpenicillin with a decrease of the concentration in liver and kidney. Accumulation in corresponding tissue slices was reduced by probenecid. Therefore, the well known increase of penicillin in plasma after probenecid seems to be not only due to an inhibition of renal excretion but also to a reduced tissue uptake in liver and kidney.     

Effect of taurine administration on liver lipids in guinea pig

Summary The oral administration of 0.4% taurine in drinking water for 14 consecutive days showed the following hepatic effects in male guinea pig. The percentage of tauro-conjugated biliary bile acids was increased from 17.2–54.2%; the ratio liver weight/body weight was increased, and fatty change was induced. Liver triglyceride concentration was accordingly increased; diglyceride and phosphatidylcholine concentrations were reduced by the treatment, while phosphatidylethanolamine level was not affected. These changes suggest an adverse effect of taurine administration on phosphatidylcholine hepatic synthesis.     

Influence of phenobarbital and TCDD on the hepatic metabolism of TCDD in the dog

Summary The influence of phenobarbital and TCDD pretreatment on the formation and biliary excretion of TCDD-metabolites following single doses of³H-TCDD was investigated. Without pretreatment, 24.5% of the absorbed³H-TCDD dose was excreted in the bile within 110 h. Phenobarbital did not influence this rate, whereas a single dose of 10 g of unlabeled TCDD/kg b.wt nine days earlier resulted in a doubling of the amount of radioactive material eliminated in the bile (47.4%).     

Influence of phenobarbital and TCDD on the hepatic metabolism of TCDD in the dog

The influence of phenobarbital and TCDD pretreatment on the formation and biliary excretion of TCDD-metabolites following single doses of 3H-TCDD was investigated. Without pretreatment, 24.5% of the absorbed 3H-TCDD dose was excreted in the bile within 110 h. Phenobarbital did not influence this rate, whereas a single dose of 10 micrograms of unlabeled TCDD/kg b.wt nine days earlier resulted in a doubling of the amount of radioactive material eliminated in the bile (47.4%).     

Circadian rhythm of bile secretion in the rat.

In rats the bile flow and the estimated bile acid independant flow (BAIF) were significantly lower at 17.00 h than at 08.00 and 24.00 h. The decrease in BAIF paralleled the decrease in liver weight. Bile acid excretion was not different.     

The effect of five proteins on stem cells used for osteoblast differentiation and proliferation: a current review of the literature

Bone-tissue engineering is a therapeutic target in the field of dental implant and orthopedic surgery. It is therefore essential to find a microenvironment that enhances the growth and differentiation of osteoblasts both from mesenchymal stem cells (MSCs) and those derived from dental pulp. The aim of this review is to determine the relationship among the proteins fibronectin (FN), osteopontin (OPN), tenascin (TN), bone sialoprotein (BSP), and bone morphogenetic protein (BMP2) and their ability to coat different types of biomaterials and surfaces to enhance osteoblast differentiation. Pre-treatment of biomaterials with FN during the initial phase of osteogenic differentiation on all types of surfaces, including slotted titanium and polymers, provides an ideal microenvironment that enhances adhesion, morphology, and proliferation of pluripotent and multipotent cells. Likewise, in the second stage of differentiation, surface coating with BMP2 decreases the diameter and the pore size of the scaffold, causing better adhesion and reduced proliferation of BMP-MSCs. Coating oligomerization surfaces with OPN and BSP promotes cell adhesion, but it is clear that the polymeric coating material BSP alone is insufficient to induce priming of MSCs and functional osteoblastic differentiation in vivo. Finally, TN is involved in mineralization and can accelerate new bone formation in a multicellular environment but has no effect on the initial stage of osteogenesis.     

Sympathectomy enhances the substance P-mediated breakdown of the blood-aqueous barrier in response to infrared irradiation of the rabbit iris

Summary Rabbits were subjected to infrared irradiation of the iris 1 month after unilateral cervical sympathectomy. The resulting breakdown of the blood-aqueous barrier was greatly enhanced on the sympathectomized side. In contrast, the response to intravitreally injected substance P (SP) was the same in both eyes. The enhancement of the response to IR irradiation could be abolished by pretreatment with an SP antagonist, (D-Pro², D-Trp^7,9)-SP.This study was supported by grants from the Swedish MRC (04X-1007, 14X-2321), the Medical Faculty of Lund, Ferring Arzneimitel, Kiel (Federal Republic of Germany) and Ferring Pharmaceuticals, Malmö (Sweden).