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PubMed2003

Ranitidine treatment during a modest inflammatory response precipitates idiosyncrasy-like liver injury in rats.

Drug idiosyncrasy is an adverse event of unknown etiology that occurs in a small fraction of people taking a drug. Some idiosyncratic drug reactions may occur from episodic decreases in the threshold for drug hepatotoxicity. Previous studies in rats have shown that modest underlying inflammation triggered by bacterial lipopolysaccharide (LPS) can decrease the threshold for xenobiotic hepatotoxicity. The histamine-2 (H2)-receptor antagonist ranitidine (RAN) causes idiosyncratic reactions in people, with liver as a usual target. We tested the hypothesis that RAN could be rendered hepatotoxic in animals undergoing a modest inflammatory response. Male rats were treated with a nonhepatotoxic dose of LPS (44 x 10(6) endotoxin units/kg i.v.) or its vehicle and then 2 h later with a nonhepatotoxic dose of RAN (30 mg/kg i.v.) or its vehicle. Liver injury was evident only in animals treated with both RAN and LPS as estimated by increases in serum alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase activities within 6 h after RAN administration. LPS/RAN cotreatment resulted in midzonal liver lesions characterized by acute necrosuppurative hepatitis. Famotidine (FAM) is an H2-antagonist for which the propensity for idiosyncratic reactions is far less than RAN. Rats given LPS and FAM at a dose pharmacologically equipotent to that of RAN did not develop liver injury. In vitro, RAN sensitized hepatocytes to killing by cytotoxic products from activated neutrophils, whereas FAM lacked this ability. The results indicate that a response resembling human RAN idiosyncrasy can be reproduced in animals by RAN exposure during modest inflammation.

Animals↗

PubMed2004

Organ injury and cytokine release caused by peptidoglycan are dependent on the structural integrity of the glycan chain.

Several studies have implicated a role of peptidoglycan (PepG) as a pathogenicity factor in sepsis and organ injury, in part by initiating the release of inflammatory mediators. We wanted to elucidate the structural requirements of PepG to trigger inflammatory responses and organ injury. Injection of native PepG into anesthetized rats caused moderate but significant increases in the levels of alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, and bilirubin (markers of hepatic injury and/or dysfunction) and creatinine and urea (markers of renal dysfunction) in serum, whereas PepG pretreated with muramidase to digest the glycan backbone failed to do this. In an ex vivo model of human blood, PepG containing different amino acids induced similar levels of the cytokines tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), IL-8, and IL-10, as determined by plasma analyses (enzyme-linked immunosorbent assay). Hydrolysis of the Staphylococcus aureus cross-bridge with lysostaphin resulted in moderately reduced release of TNF-alpha, IL-6, IL-8, and IL-10, whereas muramidase digestion nearly abolished the ability to induce cytokine release and IL-6 mRNA accumulation in CD14(+) monocytes compared to intact PepG. However, additional experiments showed that muramidase-treated PepG synergized with lipopolysaccharide to induce TNF-alpha and IL-10 release in whole blood, despite its lack of inflammatory activity when administered alone. Based on these studies, we hypothesize that the structural integrity of the glycan chain of the PepG molecule is very important for the pathogenic effects of PepG. The amino acid composition of PepG, however, does not seem to be essential for the inflammatory properties of the molecule.

Actinomycetales↗

PubMed1991

Biological effect monitoring of occupational exposure to 1,3-dichloropropene: effects on liver and renal function and on glutathione conjugation.

A prospective study was performed in the Dutch flower bulb culture to investigate the possible effects of subchronic exposure to the soil fumigant 1,3-dichloropropene (DCP) on liver and kidney function and on glutathione conjugation capacity in blood. Urine spot samples and venous blood samples from 14 workers applying DCP (applicators) were taken at the start of the season in July, and after the season in October. The parameters of liver function measured were: alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, gamma-glutamyltranspeptidase, and total bilirubin (conjugated and unconjugated). Total bilirubin was significantly decreased from 9.5 before to 7.0 mumol/l after the season. In combination with an increase in serum gamma-glutamyltranspeptidase activity from 12.5 to 19.5 U/l this indicates moderate hepatic enzyme induction. To study renal function, creatinine and beta 2-microglobulin in serum, and beta 2-microglobulin, albumin, alanine aminopeptidase, beta-galactosidase, and retinol binding protein in urine were measured. The glomerular function parameters albumin in urine and creatinine in serum changed significantly during the season: albumin concentration increased from 5.2 to 7.6 mg/l, whereas creatinine concentration [corrected] decreased from 93.0 to 87.5 mumol/l. The tubular function parameter retinol binding protein also increased in concentration from 20.0 to 26.9 micrograms/l. Therefore, a subclinical nephrotoxic effect of subchronic exposure to DCP cannot be excluded. Effects on glutathione conjugation capacity were studied by measuring erythrocyte glutathione S-transferase activity and blood glutathione concentrations. The activity of glutathione S-transferase in erythrocytes was significantly decreased from 4.7 before to 3.3 U/g haemoglobin after the season. The same was true for the blood glutathione concentrations, which decreased from 0.93 to 0.82 mM.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Neuropsychological symptoms and occupational exposure to anaesthetics.

OBJECTIVE: To analyse the relation between symptoms regularly reported by hospital personnel and exposure to anaesthetics. SETTING: Personnel of 18 hospitals in Paris from 1987 to 1989. DESIGN: An exposed group that included all operating theatre members except for doctors, and which was divided into three subgroups depending on the degree of exposure--exposure was measured by the frequency of the use of the scavenging system--and a control group that included other hospital personnel matched by hospital, sex, occupation, age, and duration of service. SUBJECTS: 557 exposed workers and 566 unexposed workers. MAIN OUTCOME MEASURES: The groups were compared according to the crude rates of regular symptoms. Adjusted odds ratios were calculated to estimate the risks associated with exposure to anaesthetic gas. Liver transaminase activities (alanine aminotransferase, aspartate aminotransferase (s-ASAT, and gamma-glutamyl transpeptidase) were measured and compared between groups of exposure. RESULTS: After controlling for working conditions and matching factors, neuropsychological symptoms and tiredness were reported more by workers in less often scavenged theatres than by controls. No difference was found between workers of the well scavenged theatres and controls. Among the exposed workers, the members of paediatric surgical staffs reported a higher rate of neurological complaints (tingling, numbness, cramps) and tiredness than the members of the other surgical staffs. They had a high value of s-ASAT more frequently than the other exposed workers. CONCLUSION: These results strengthen the hypothesis of a causal relation between exposure to anaesthetics and neuropsychological symptoms, and show a dose-response effect. They suggest that the use of ventilating systems in operating rooms is an effective means of prevention.

Anesthetics↗

PubMed1990

Hypothermia, hepatic oxygen supply-demand, and ischemia-reperfusion injury in pigs.

We examined the effects of two degrees of hypothermia on hepatic oxygen delivery and uptake, hepatic lactate uptake as a marker of hepatic function, and the effect of hypothermia on ischemia-reperfusion injury in the liver in miniature pigs (n = 18, 21-30 kg body wt). Hepatic arterial and portal venous blood flows were measured while hepatic oxygen delivery was progressively decreased without venous congestion in the preportal area. With decreases in hepatic blood and oxygen supply, oxygen extraction gradually increased from 50 to 90% in the normothermic group and from 25 to 70 and 84% in the hypothermic (30. and 34 degrees C, respectively) groups. The values of critical hepatic oxygen delivery were between 7.3 and 11.9 ml O2.min-1.100 g-1 without significant differences among the groups. During reperfusion after ischemic insult, hepatic oxygen uptake returned to base-line values in both hypothermic groups but remained substantially below base-line values in normothermic groups of animals. Hepatic enzyme concentrations (lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, and alcohol dehydrogenase) were substantially increased (up to 30-fold) in normothermic animals, but the concentrations did not increase in either of the hypothermic groups. These results demonstrated that hypothermia per se does not affect hepatic oxygen delivery but decreases hepatic oxygen demand and uptake, provides an effective protection from hepatic oxygen deprivation, and lessens reperfusion injury.

Animals↗

PubMed2006

A3 adenosine receptor activation decreases mortality and renal and hepatic injury in murine septic peritonitis.

The role of A3 adenosine receptors (ARs) in sepsis and inflammation is controversial. In this study, we determined the effects of A3AR modulation on mortality and hepatic and renal dysfunction in a murine model of sepsis. To induce sepsis, congenic A3AR knockout mice (A3AR KO) and wild-type control (A3AR WT) mice were subjected to cecal ligation and double puncture (CLP). A3AR KO mice had significantly worse 7-day survival compared with A3AR WT mice. A3AR KO mice also demonstrated significantly higher elevations in plasma creatinine, alanine aminotransferase, aspartate aminotransferase, keratinocyte-derived chemokine, and TNF-alpha 24 h after induction of sepsis compared with A3AR WT mice. Renal cortices from septic A3AR KO mice exhibited increased mRNA encoding proinflammatory cytokines and enhanced nuclear translocation of NF-kB compared with samples from A3AR WT mice. A3AR WT mice treated with N6-(3-iodobenzyl)ADO-5'N-methyluronamide (IB-MECA; a selective A3AR agonist) or 3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1,4-(+/-)-dihydropyridine-3,5-dicarboxylate (MRS-1191; a selective A3AR antagonist) had improved or worsened 7-day survival after induction of sepsis, respectively. Moreover, A3AR WT mice treated with IB-MECA or MRS-1191 showed acutely improved or worsened, respectively, renal and hepatic function following CLP. IB-MECA significantly reduced mortality in mice lacking the A1AR or A2aAR but not the A3AR, demonstrating specificity of IB-MECA in activating A3ARs and mediating protection against sepsis-induced mortality. We conclude that endogenous or exogenous A3AR activation confers significant protection from murine septic peritonitis primarily by attenuating the hyperacute inflammatory response in sepsis.

Acute Kidney Injury↗

PubMed1987

Hepatic function in rats after spaceflight: effects on lipids, glycogen, and enzymes.

The inclusion of rats aboard Spacelab 3 (SL-3) allowed analyses of liver lipids, glycogen, hepatic enzymes of cholesterol, glycerolipid and sphingolipid biosynthesis, and other enzyme activities. Glycogen content was markedly elevated in livers from the flight animals compared with controls. Cholesterol was 24% (P less than 0.04) lower in livers from the experimental groups, whereas blood cholesterol was 19% higher (P less than 0.05). The activity of 3-hydroxy-3-methylglutaryl-CoA reductase, the rate-limiting enzyme of steroid biosynthesis, was 80% lower (P less than 0.01). Total phospholipids and sphingolipid levels did not differ significantly. The specific activity of fatty acyl-CoA synthetase, which is responsible for activation of fatty acids, was 37% (P less than 0.05) higher in microsomes from the rats on SL-3; however, since these animals had 25% less microsomal protein (P less than 0.02), there was no difference per gram of liver. The initial enzymes of sphingolipid and glycerolipid biosynthesis were assayed; serine palmitoyltransferase was 40% lower (P less than 0.01), and glycerol 3-phosphate acyltransferase did not differ. Hepatic cytochrome P-450 content decreased by 50% after spaceflight. Enzymes that did not differ significantly between the two groups include cytochrome b5, glutathione S-transferase, tyrosine aminotransferase, aspartate aminotransferase, and cystathionase. These findings suggest that spaceflight alters hepatic metabolism of several classes of compounds.

Animals↗

PubMed2005

A1 adenosine receptor knockout mice exhibit increased mortality, renal dysfunction, and hepatic injury in murine septic peritonitis.

Sepsis is a leading cause of multiorgan dysfunction and death in hospitalized patients. Dysregulated inflammatory processes and apoptosis contribute to the pathogenesis of sepsis-induced organ dysfunction and death. A(1) adenosine receptor (A(1)AR) activation reduces inflammation and apoptosis after ischemia-reperfusion injury. Therefore, we questioned whether A(1)AR-mediated reduction of inflammation and apoptosis could improve mortality and organ dysfunction in a murine model of sepsis. A(1)AR knockout mice (A(1) knockout) and their wild-type (A(1) wild-type) littermate controls were subjected to cecal ligation and double puncture (CLP) with a 20-gauge needle. A(1) knockout mice or A(1) wild-type mice treated with 1,3-dipropyl-8-cyclopentylxanthine (a selective A(1)AR antagonist) had a significantly higher mortality rate compared with A(1) wild-type mice following CLP. Mice lacking endogenous A(1)ARs demonstrated significant elevations in plasma creatinine, alanine aminotransferase, aspartate aminotransferase, keratinocyte-derived chemokine, and tumor necrosis factor-alpha 24 h after induction of sepsis compared with wild-type mice. The renal corticomedullary junction from A(1) knockout mice also exhibited increased myeloperoxidase activity, intercellular adhesion molecule-1 protein, and mRNA encoding proinflammatory cytokines compared with renal samples from A(1) wild-type littermate controls. No difference in renal tubular apoptosis was detected between A(1) knockout and A(1) wild-type mice. We conclude that endogenous A(1)AR activation confers a protective effect in mice from septic peritonitis primarily by attenuating the hyperacute inflammatory response in sepsis.

Animals↗

PubMed1999

Acute pseudohepatitis in a chronic substance abuser secondary to occult seat belt injury.

Causes of a massive elevation in serum aminotransferases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) in the substance-abusing patient include viral hepatitis and drug hepatotoxicity. A patient chronically addicted to injection heroin and cocaine presented to the emergency room in a confused state and was admitted to a medical ward with an AST of 4120 U/L, ALT 3820 U/L and right upper quadrant discomfort. Investigations for viral and hepatotoxic causes for the liver dysfunction revealed only hepatitis C seropositivity. A computed tomogram of the abdomen, however, revealed a significant contusion to the right lobe of the liver consistent with traumatic injury. A motor vehicle accident, in which the patient was wearing a seat belt, and which had occurred a few days before admission and had been thought to be minor, was the cause of the liver dysfunction. Significant blunt abdominal traumatic injuries are usually managed exclusively by surgical trauma units. This case underlines the need for medical specialists to be aware of hepatic contusion injuries and to have a high index of suspicion when investigating unexplained hepatocellular dysfunction in chronic substance abusers who have been in motor vehicle accidents.

Accidents, Traffic↗

PubMed2003

Use of olive oil based emulsions as an alternative to soybean oil based emulsions in total parenteral nutrition and their effects on liver regeneration following hepatic resection in rats.

BACKGROUND/AIM: The main objective of this study was to compare the effects of olive oil to those of soybean oil on liver tissue regeneration following hepatic resection in rats. METHODS: Seventy albino Wistar rats were randomly assigned to seven groups which contained 10 rats each. Group 1 was the sham-treated group; groups 2 and 3 received total parenteral nutrition (TPN) containing soybean oil lipid emulsions (20% Lipofundin MCT/LCT) for 48 or 72 h; groups 4 and 5 received TPN containing olive oil (80%)/soybean oil (20%) lipid emulsions (ClinOleic 20%) for 48 or 72 h; group 6 was the control group for 48 h, and group 7 was the control group for 72 h. TPN was given via internal jugular vein, and 70% hepatic resection was performed in the study groups. In addition, hepatic resections with no TPN were performed in the control groups, except the sham group. Relative liver weight, mitotic index, proliferating cell nuclear antigen labeling index, and carnitine levels in liver tissue samples were used to assess hepatic regeneration. Thiobarbituric acid reactive substances were measured as an index of lipid peroxidation and oxidative tissue damage. Alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase were parameters for the liver function. RESULTS: The relative liver weight increased significantly with minimal hepatosteatosis in the olive oil treated groups. Lipid peroxidation significantly decreased with near-normal serum levels of the liver function parameters in the olive oil/soybean oil treated groups, and mitotic index and proliferating cell nuclear antigen labeling index reached their maximum level in rats receiving TPN containing any kind of lipid emulsions for 48 h following resection. CONCLUSIONS: The use of olive oil/soybean oil lipid emulsions in TPN has important beneficial effects on the liver regeneration, and the antioxidant properties of olive oil originating from its natural components indirectly contribute to the liver regeneration in rats.

Animals↗

PubMed1992

Effect of different protein diets on the distribution of amino acids in plasma, liver and brain in the rat.

The distribution of amino acids between plasma, liver and brain was studied in adult male rats, fed a diet containing 8.7, 17 (control animals), 32 and 51% of protein during 15 days. The caloric intake was nearly equal in all groups. The highest food intake was observed in the animals on the low protein diet. Changes in plasma amino acids were variable. In contrast to the behavior of most amino acids in plasma, the branched chain amino acids were highest in the animals fed the 51% protein diet. Despite the low protein intake in the animals fed a 8.7% protein diet, the concentration of serine, glutamic acid, glutamine, glycine, alanine, methionine, isoleucine, leucine, phenylalanine and ornithine were significantly higher compared to control animals, whereas in those receiving a high protein diet, valine, leucine, tyrosine, tryptophan and histidine increased in relation to the increased protein and amino acid intake. The plasma amino acid patterns are not greatly influenced by the amino acid distribution in the food and the amount ingested. Alanine aminotransferase, aspartate aminotransferase, glutamate dehydrogenase and cholinesterase showed a two- to fivefold increased activity in the liver of animals consuming a high protein diet. In the brain, the concentration of valine, leucine, isoleucine, phenylalanine and tyrosine in animals receiving the low protein diet was higher than in controls and increased further with increasing protein content of the diet. Glutamine was increased in all dietary groups. The predicted influx of amino acids showed increasing influx rates in dependence of the plasma amino acid concentration. The entry of tyrosine and tryptophan and their brain concentration was inversely proportional to the protein content of the diet. In the present study which considers long-term adaptation to an increasing protein and amino acid intake in comparison to a balanced control protein diet, the levels of the indispensable amino acids were maintained within narrow limits in the brain and liver. The results indicate that inspite of a variable protein intake, the body tends to keep organ amino acids in relatively narrow limits favoring in this way amino acid homeostasis.

Amino Acids↗

PubMed1989

Variation in some enzymes in amniotic fluid and maternal serum during pregnancy.

The following 10 enzymes were assayed in 187 amniotic fluid and maternal serum samples at 15-42 weeks of gestation: alkaline phosphatase, heat-stable alkaline phosphatase (only in amniotic fluid), acid phosphatase, alanine aminotransferase, aspartate aminotransferase, alpha-amylase, gamma-glutamyltransferase, creatine kinase, lactate dehydrogenase, and lysozyme. The normal reference ranges are reported for amniotic fluid and maternal serum enzymes, together with the abnormal values accompanying neural tube defects and EPH-gestosis. The determination of gamma-glutamyltransferase, heat-stable alkaline phosphatase and creatine kinase was found to be of appreciable diagnostic significance in clinical practice.

Amniotic Fluid↗

PubMed2003

Hepatoprotection by the farnesoid X receptor agonist GW4064 in rat models of intra- and extrahepatic cholestasis.

Farnesoid X receptor (FXR) is a bile acid-activated transcription factor that is a member of the nuclear hormone receptor superfamily. Fxr-null mice exhibit a phenotype similar to Byler disease, an inherited cholestatic liver disorder. In the liver, activation of FXR induces transcription of transporter genes involved in promoting bile acid clearance and represses genes involved in bile acid biosynthesis. We investigated whether the synthetic FXR agonist GW4064 could protect against cholestatic liver damage in rat models of extrahepatic and intrahepatic cholestasis. In the bile duct-ligation and alpha-naphthylisothiocyanate models of cholestasis, GW4064 treatment resulted in significant reductions in serum alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase, as well as other markers of liver damage. Rats that received GW4064 treatment also had decreased incidence and extent of necrosis, decreased inflammatory cell infiltration, and decreased bile duct proliferation. Analysis of gene expression in livers from GW4064-treated cholestatic rats revealed decreased expression of bile acid biosynthetic genes and increased expression of genes involved in bile acid transport, including the phospholipid flippase MDR2. The hepatoprotection seen in these animal models by the synthetic FXR agonist suggests FXR agonists may be useful in the treatment of cholestatic liver disease.

ATP Binding Cassette Transporter, Subfamily B↗

PubMed2002

Implications for altered glutamate and GABA metabolism in the dorsolateral prefrontal cortex of aged schizophrenic patients.

OBJECTIVE: Pharmacological, clinical, and postmortem studies suggest altered gamma-aminobutyric acid (GABA)-ergic and glutamatergic function in patients with schizophrenia. The dorsolateral prefrontal cortex is one key locus of abnormality. The precise neurochemical mechanisms underlying neurotransmitter alterations, such as hypoglutamatergia or GABA dysfunction, are not well understood. This study investigated key biochemical elements of GABA and glutamate metabolism in brain specimens from schizophrenic patients. The activities of nine principal GABA and glutamate-associated metabolic enzymes were measured concurrently in the dorsolateral prefrontal cortex of antemortem-assessed and neuropathologically characterized schizophrenic and comparison subjects. METHOD: Postmortem dorsolateral prefrontal cortex specimens from schizophrenia, Alzheimer's disease, and normal nonpsychiatric comparison subjects were assayed to determine activities of the principal glutamate and GABA-metabolizing enzymes glutamine synthetase, glutamate dehydrogenase, alpha-ketoglutarate dehydrogenase, phosphate-activated glutaminase, alanine aminotransferase, aspartate aminotransferase, glutamic acid decarboxylase, GABA-transaminase, and succinic semialdehyde dehydrogenase. RESULTS: Glutamic acid decarboxylase activities were twofold greater and phosphate-activated glutaminase activities were fourfold greater in the schizophrenic group than in the comparison group. Differences in postmortem interval, tissue pH, inhibition of phosphate-activated glutaminase, and medication effects could not account for the differences. Differences in phosphate-activated glutaminase and glutamic acid decarboxylase activities in equivalent specimens from Alzheimer's patients were not observed. The activities of the remaining enzymes were unchanged. CONCLUSIONS: Greater phosphate-activated glutaminase and glutamic acid decarboxylase activities, specific to schizophrenia patients, provide additional biochemical evidence that dorsolateral prefrontal cortex glutamate and GABA metabolism is altered in schizophrenic subjects. These greater activities are consistent with models of a dysregulated glutamatergic/GABA-ergic state in schizophrenia.

Age Factors↗

PubMedDate not supplied

Hepatotoxicity in guinea pigs following acute inhalation exposure to 1,1-dichloro-2,2,2-trifluoroethane.

Groups of 10 male Hartley guinea pigs were exposed to 3.0, 2.0, 1.0, or 0.1% (v/v) 1,1-Dichloro-2,2,2-trifluoroethane (HCFC-123) or 1.0% (v/v) halothane by inhalation for 4 hr. A sixth group of 10 guinea pigs received only air. All animals were sacrificed 48 hr postexposure. Gross and histopathologic examination of the liver, heart, and kidney and routine hematology and clinical chemistry analyses [including isocitrate dehydrogenase (ICDH)] were done on all guinea pigs. Lesions related to HCFC-123 and halothane exposure were limited to the liver and included centrolobular vacuolar (fatty) change, multifocal random degeneration and necrosis, and centrolobular degeneration and necrosis. These lesions were observed in 90-100% of the exposed animals and were absent in the air-only controls. There was significant individual animal variation in susceptibility to both HCFC-123 and halothane, resulting in a spectrum of histologic lesions and clinical chemistry values within each exposure group. Alanine aminotransferase, aspartate aminotransferase, and ICDH were the most significant predictors of hepatocellular damage. Similarities in the response between halothane and HCFC-123 in this guinea pig model suggests that humans susceptible to halothane-induced hepatitis may be susceptible to HCFC-123 by a common mechanism of toxicity.

Administration, Inhalation↗

PubMedDate not supplied

Treatment of chronic liver disease with ursodeoxycholic acid.

Evidence is accumulating that ursodeoxycholic acid (UDCA), an agent widely employed for gallstone dissolution, exerts therapeutic effects in chronic liver disease. UDCA is thought to act mainly by reducing the detergent properties of bile, making it less toxic for the liver cells. Confirming the results of preliminary observations double-blind, placebo-controlled trials have shown that UDCA significantly decreased serum concentrations of liver enzymes such as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and gamma-glutamyl transferase in primary biliary cirrhosis and other cholestatic conditions, as well as in chronic active hepatitis. A substantial improvement in liver histology has also been detected in UDCA-treated patients with primary biliary cirrhosis. The effect of UDCA in chronic hepatitis is currently a matter of investigation.

Cholestasis↗

PubMed2002

Serum bilirubin levels in 1-month-old, healthy, term infants from southern Turkey.

This study investigated bilirubin levels in 282 1-month-old, healthy, term infants from the Adana region in southern Turkey. Total bilirubin was > 5 mg/dl in 20.2% of the infants and > 10 mg/dl in 6% of the group. Thyroid function and levels of alanine aminotransferase, aspartate aminotransferase and glucose-6-phosphate dehydrogenase were determined in babies with bilirubin levels > 5 mg/dl. The results were normal in all but one case, an infant with a bilirubin level of > 10 mg/dl and glucose-6-phosphate dehydrogenase deficiency. The results indicate that in this population a 5-mg/dl cut-off level for further investigation would mean that 20% of all infants would require further evaluation. This is not cost-effective. Based on our findings, we suggest that the cut-off level for investigating prolonged jaundice in term, 1-month-old, healthy infants in the Turkish population should be > 5 mg/dl.

Bilirubin↗

PubMed2006

Monosodium glutamate-induced oxidative damage and genotoxicity in the rat: modulatory role of vitamin C, vitamin E and quercetin.

Monosodium glutamate (MSG) continues to function as a flavor enhancer in West African and Asian diets. The present study examines the modulatory effects of dietary antioxidant vitamin C (VIT C), vitamin E (VIT E) and quercetin on MSG-induced oxidative damage in the liver, kidney and brain of rats. In addition, the effect of these antioxidants on the possible genotoxicity of MSG was investigated in a rat bone marrow micronuclei model. MSG administered intraperitoneally at a dose of 4 mg/g body wt markedly increase malondialdehyde (MDA) formation in the liver, the kidney and brain of rats. Simultaneous administration of VIT C, VIT E and quercetin to MSG-treated rats significantly reduced this increase in MDA induced by MSG. VIT E reduced lipid peroxidation most in the liver followed by VIT C and then quercetin, while VIT C and quercetin showed a greater ability to protect the brain from membrane damage than VIT E. The decreased glutathione (GSH) level elicited by MSG in the three organs corresponded with marked increase in the activity of glutathione-S-transferase (GST). While MSG increased (P < 0.001) the activities of superoxide dismutase and catalase in the liver, it decreased significantly the activities of these enzymes in the kidney and the brain. The three antioxidants were effective at ameliorating the effects of MSG on GSH levels and the enzymes in the three organs examined. While MSG increased the activity of glucose-6-phosphatase in the liver and kidneys of rats (P < 0.001), the activity of the enzyme was abysmally low in the brain. There were marked increases in the activities of alanine aminotransferase, aspartate aminotransferase and gamma-glutamyl transferase in rats treated with MSG. The antioxidants tested protected against MSG-induced liver toxicity significantly. MSG at a dose of 4 mg/g significantly (P < 0.01) induced the formation of micronucleated polychromatic erythrocytes (MNPCEs). Co-treatment of rats with VIT C and quercetin inhibited the induction of MNPCEs by MSG (P < 0.001). VIT E failed to protect against MSG-induced genotoxicity. The results indicate that dietary antioxidants have protective potential against oxidative stress induced by MSG and, in addition, suggest that active oxygen species may play an important role in its genotoxicity.

Animals↗