Serum GPT Research Articles

DISAPPEARANCE OF HBeAG IN FIVE CASES OF HBV CARRIER

Five HBV carriers in whom HBeAg disappeared without any special therapy are reported. Four of these seroconverted to anti-HBe later on. Serum GPT levels in these five cases were abnormally elevated for a variable period (34.8± 11.6 months ; mean±SD), but returned to normal levels coinciding with the disappearance of HBeAg. In three cases liver biopsy was performed. The histology showed persistent hepatitis in one case and chronic active hepatitis in two. In summary, clinical features before the disappearance of HBeAg were not distinguishable from those of chronic hepatitis.It is suggested that in pediatric HBeAg-positive HBV carriers with overt liver dysfunction, HBeAg is prone to disappear without any special therapy and, therefore, therapy with corticosteroid may not be indicated.

Role of peptide-leukotrienes in liver injury in mice.

The role of peptide leukotrienes (p-LTs), especially LTC4 and LTD4 in liver disease, was investigated in mice experimental liver injury models. The liver injury was induced by the injection of bacterial lipopolysaccharide (LPS) into Corynebacterium parvum pretreated mice. Carbon tetrachloride (CCl4)-induced liver injury in mice was used as a standard model. In both injury models, extensive liver parenchymal cell damage was observed by the elevation of glutamate transaminase (GOT and GPT) activity and confirmed by significant histopathological changes in the liver. Moreover, significant elevation of LTC4 in the liver was observed in both models 1 and 6 h after the onset of disease. Administration of AA-861, a selective 5-lipoxygenase inhibitor (0.5, 1, and 2 mg/kg) and LY-171883, a p-LT receptor antagonist (50 and 200 mg/kg) suppressed the elevation of serum GOT and GPT levels and histopathological changes in both experimental liver injury models. In addition, when authentic LTC4 or LTD4 was injected into the mouse, clear elevation of serum GOT and GPT and histopathological changes of the liver were observed. These results suggest that p-LTs play a role in the onset of liver diseases in mice.

The role of thromboxane A 2 [TxA 2] in liver injury in mice

The role of thromboxane A 2 (TxA 2) in CCl 4-induced liver disease was investigated in mice. Significant elevation of TxB 2 in the liver was observed 6 hours after the injection of CCl 4. Administration of OKY-046, a selective TxA 2 synthetase inhibitor (10 and 50 mg/kg) and ONO-3708, a TxA 2 receptor antagonist, (0.5, 1 and 2 mg/Kg) suppressed the elevation of serum GOT and GPT levels and histopathological changes of the liver. In addition, OKY-046 inhibited the elevation of TxB 2 in the liver. When U-46619, a stable TxA 2 mimetic was injected i.v. into the mice, clear elevation of serum GOT and GPT levels and histopathological score of the liver were observed. These results suggest that TxA 2 play a role for the onset of CCl 4-induced liver injury in mice.

Preventive effect of traditional herbal medicine, shosaiko-to, on danazol-induced hepatic damage

The incidence of the hepatic damage during treatment with danazol (D), indicated by increased serum GOT, GPT and LDH levels, has been shown to be high especially in Japan. Thus, the preventive effect of the traditional herbal medicine, shosaiko-to (SS) was investigated in the administration of D and SS for 16 weeks (D + SS group, N = 9) and the pre-administration of SS for about 4 weeks followed by D and SS for 16 weeks (SS → D + SS group, N = 15). The incidence of serum GOT, GPT and LDH levels of more than normal range during the administration of danazol in the D + SS group was similar to that in the previous study of the administration of D alone. But it was significantly lower in the SS → D + SS group than the D + SS group. The mean levels of serum GOT and GPT were much lower in the SS → D + SS group than the D + SS group throughout the administration of danazol and the difference was significant at 8, 10 and 12 weeks in serum GOT levels and at 4 weeks in serum GPT levels. These results indicate that the pre-administration of SS has great efficacy in the prevention of danazol-induced hepatic damage.

Changes in Liver Function Tests in Patients with Inflammatory Bowel Disease on Enteral Nutrition

Morphologic and functional hepatic changes occur in inflammatory bowel disease (IBD). Patients with this disease often require the administration of artificial nutritional support. Liver function tests (LFT) derangement is a widely recognized side-effect of total parenteral nutrition (TPN). Therefore, the use of this modality of nutritional support may be an additional factor to cause hepatic damage in IBD patients. However whether or not the same occurs in patients receiving total enteral nutrition (TEN) is not well-established. The aim of the present study was to evaluate the effect of TEN upon LFT in patients with moderate to severe acute attacks of IBD, by means of a prospective, controlled, and nonrandomized design. Forty-nine patients were included; 29 (11 patients with ulcerative colitis and 18 with Crohn's disease) received TEN, and 20 (11 with ulcerative colitis and 9 with Crohn's disease) did not. Both groups were homogeneous regarding age, sex, disease activity index, nutritional status, and length of the study (24.8 +/- 1.3 vs 23.9 +/- 16.8 days). In all cases, weekly measurements of serum alkaline phosphatase, GOT, and GPT were performed. There were no significant differences in LFT at the beginning of the study between groups. The percentage of patients showing derangement of some LFT during the study did not differ between both groups: six of 29 (20.6%) in TEN group vs three of 20 (15%) in control group. Six out of the nine patients (in both groups) who developed LFT derangement had one or more causes, other than TEN for explaining hepatic dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship between hepatic glutathione content and carbon tetrachloride-induced hepatotoxicity in vivo

The relationship between carbon tetrachloride (CCl 4)-induced hepatotoxicity and hepatic glutathione (GSH) content was investigated in fed and fasted rats. The elevation of serum glutamic-pyruvic transaminase (GTP) activity by CCl 4 treatment was enhanced by fasting. Although the hepatic GSH content fo 12-hour-fasted rats was higher than that of fed rats determined at 6 p.m., the serum GPT activity of the former was higher than that of the latter. Starvation had no effect on the activities of hepatic glutathione peroxidase (GSH-Px) and glutathione reductase (GR). The results suggest that the potentiation of hepatic injury by CCl 4 cannot be related to hepatic GSH content.

Effect of alpha-naphthyl isothiocyanate and CCl4 interaction on hepatocellular calcium transport

Alpha-naphthyl isothiocyanate (ANIT), and CCl/sub 4/ are both hepatotoxic agents but with different mechanisms of action. In recent years, much attention has been focused on the disruption of intracellular calcium homeostasis as a common ultimate mechanism of the chemical induced irreversible hepatocellular damage. Calcium is known to accumulate in necrotic tissues. The extracellular fluid is rich in calcium whereas the concentration of the intracellular calcium is much lower. Therefore, it is believed that any damage to plasma membrane will result in an influx of calcium. Calcium ions are biologically very active, being capable of considerable disruption of metabolic order. Agents such as CCl/sub 4/, BrCCl/sub 3/ which cause hepatocellular necrosis have also been reported to perturb the intracellular calcium homeostasis. The present study was designed to determine the effect of intrahepatic cholestasis as produced by a single toxic dose of ANIT on CCl/sub 4/ induced hepatotoxicity and hepatocellular calcium uptake. /sup 45/Ca uptake in the isolated mitochondria and microsomes using three different doses of CCl/sub 4/ known to be toxic was measured in ANIT pretreated animals. Calcium ATPase in these organelles was assayed. Microsomal cytochrome P-450 and the levels of serum GPT and Bilirubin were also determined.

Effect of OKY-046 and ONO-3708 on liver injury in mice.

The effects of OKY-046, a selective thromboxane A2 (TXA2) synthetase inhibitor, and ONO-3708, a novel TXA2 receptor antagonist, on liver disease were investigated in mice. The liver injury was induced by either an injection of antibasic liver protein (BLP) antibody into DBA/2 mice that had been previously immunized with rabbit IgG or by an injection of bacterial lipopolysaccharide (LPS) into Corynebacterium parvum (C. parvum) pretreated DDY mice. 1) In both injury models, clear elevation of glutamate transaminase (GOT and GPT) activity due to extensive liver parenchymal cell damage was observed; this was confirmed by significant histopathological changes in the liver. 2) Typical histopathological changes in the liver were submassive hepatocellular necrosis in the anti-BLP antibody-induced injury model and focal necrosis in the LPS-induced model. Inflammation and increased cell infiltration in portal connective tissue were observed in both cases. 3) Administration of OKY-046 (50 mg/kg) and ONO-3708 (0.5, 1.0 and 2.0 mg/kg) suppressed the elevation of serum GOT and GPT levels and histopathological changes in both experimental liver injury models. 4) Indomethacin inhibited the development of liver disease caused by anti-BLP antibody but not by bacterial LPS. Prostaglandin I2 inhibited the elevation of serum GOT and GPT levels and histopathological changes of the liver in the mice treated with anti-BLP antibody and showed the tendency to inhibit the development of liver injury caused by bacterial LPS.

Effect of OKY-046 and ONO-3708 on Liver Injury in Mice

The effects of OKY-046, a selective thromboxane A2 (TXA2) synthetase inhibitor, and ONO-3708, a novel TXA2 receptor antagonist, on liver disease were investigated in mice. The liver injury was induced by either an injection of anti-basic liver protein (BLP) antibody into DBA/2 mice that had been previously immunized with rabbit IgG or by an injection of bacterial lipopolysaccharide (LPS) into Corynebactehum parvum (C. parvum) pretreated DDY mice. 1) In both injury models, clear elevation of glutamate transaminase (GOT and GPT) activity due to extensive liver parenchymal cell damage was observed; this was confirmed by significant histopathological changes in the liver. 2) Typical histopathological changes in the liver were submassive hepatocellular necrosis in the anti-BLP antibody-induced injury model and focal necrosis in the LPS-induced model. Inflammation and increased cell infiltration in portal connective tissue were observed in both cases. 3) Administration of OKY-046 (50 mg/kg) and ONO-3708 (0.5. 1.0 and 2.0 mg/kg) suppressed the elevation of serum GOT and GPT levels and histopathological changes in both experimental liver injury models. 4) Indomethacin inhibited the development of liver disease caused by anti-BLP antibody but not by bacterial LPS. Prostaglandin I2 inhibited the elevation of serum GOT and GPT levels and histopathological changes of the liver in the mice treated with anti-BLP antibody and showed the tendency to inhibit the development of liver injury caused by bacterial LPS.

Effects of transfer factor on chronic hepatitis B in childhood

Nine children, 1 to 13 years of age, with HBeAg positive chronic hepatitis B received transfer factor (T.F.) monotherapy for 3 to 17 months, and were monitored by check-ups every six months from serum HBeAg, anti-HBe and GPT. In 12 months, 4 subjects became HBeAg negative and had normal serum GPT. In 22 to 48 months, 6 of the nine subjects had negative HBeAg and normal GPT, 2 had positive HBeAg and high GPT values. The remaining 1 subject who was observed for six months after T.F. therapy remained HBeAg positive with a high GPT values. No side effects were observed. These preliminary observations may indicate beneficial effects of T.F. on the natural course of chronic hepatitis B in childhood, though the ultimate effects awaits longer and well controlled clinical trials.

Glycogen storage disease with normal acid maltase: Skeletal and cardiac muscles

We report a 5-year-old boy with lysosomal glycogen storage disease and normal acid maltase activity. This patient, the fourth reported in the literature, was referred to our hospital for evaluation of elevated serum GOT, GPT, and CK activities. He had neither muscle weakness nor atrophy. Echocardiography demonstrated marked thickening of the intraventricular septum and left ventricular wall which indicated hypertrophic cardiomyopathy. Biopsied skeletal muscle disclosed massive accumulation of glycogen and autophagic vacuoles. Electron microscopy of biopsied cardiac muscle revealed severe myofibrillar disruption with marked accumulation of free and intralysosomal glycogen. Activities of all major glycolytic enzymes in skeletal muscle, including acid maltase, were normal. It is unknown why muscle lysosomes appeared to be unable to digest the trapped glycogen despite the presence of acid maltase. Our findings illustrate the importance of performing skeletal muscle investigation during childhood in patients with hypertrophic cardiomyopathy.

健常学生ボランティアにおける臨床検査正常値の検討 とくに入院管理下における血清ＧＯＴ，ＧＰＴの反復測定時の変動について

健常学生ボランティアにおける臨床検査正常値の検討 とくに入院管理下における血清ＧＯＴ，ＧＰＴの反復測定時の変動について

Clinical studies on canine dirofilarial hemoglobinuria: Measured and calculated serum osmolalities and osmolar gap.

Serum osmolalities and osmolar gap were determined in 43 normal healthy beagles (control group) and 40 dogs with dirofilarial hemoglobinuria (hemoglobinuria group). In the control group, the measured and calculated serum osmolality levels were in the means of 296 +/- 5 (SD) mOsm/kg and 293 +/- 6 mOsm/kg respectively, showing an osmolar gap less than 10 mOsm/kg. In the hemoglobinuria group, the measured serum osmolality ranged from 272 to 370 mOsm/kg. A considerable number of dogs had normal serum osmolalities in spite of severe intravascular hemolysis, suggesting that the changes in serum osmolality would not be the direct cause of intravascular hemolysis. The measured serum osmolality (331 +/- 28 mOsm/kg) was significantly higher in 11 dogs which died after a surgical removal heartworms than in 29 dogs which recovered after the removal (302 +/- 17 mOsm/kg). The calculated serum osmolality level was 296 +/- 16 mOsm/kg in 24 recovered cases, and 304 +/- 22 mOsm/kg in 10 fatal cases. The osmolar gap stayed in the normal ranges of 5.4 +/- 5.9 mOsm/kg in recovered cases, but it attained a higher level of 22.7 +/- 8.9 mOsm/kg in fatal cases, suggesting poor prognosis in cases with large osmolar gaps. There were significant positive correlations between the measured serum osmolality and osmolar gap, serum sodium, potassium, BUN, GOT, GPT, creatinine, bilirubin and plasma hemoglobin values, as well as between the osmolar gap and serum potassium, BUN, GOT, GPT, creatinine and bilirubin values. The plasma hemoglobin concentration fell markedly without significant change in serum osmolality 20 hr after the heartworm removal.

Relation between blood clearance and hepatic uptake of 99mTc-phytate in rats with hepatic injury.

The relation among the blood clearance of 99mTc-phytate (99mTc-P), the hepatic uptake of 99mTc-P and the severity of hepatic injury was investigated by using the rats with carbon tetrachloride (CCl4), D-galactosamine (Gal N), alpha-naphthylisothiocyanate (ANIT) or DL-ethionine (EthN) induced hepatic injury. After the administration of CCl4, GalN or ANIT, serum GPT activity increased significantly with the increase of dose level, and the degree of this increase was in the order: GalN greater than CCl4 greater than ANIT. However, the mild increase in serum GPT activity was observed after EthN administration. The blood clearance rate of 99mTc-P and the hepatic uptake ratio of 99mTc-P decreased with the increase of dose level after CCl4, GalN or ANIT administration, but significant changes were not found after EthN administration. The degree of decrease in the blood clearance rate of 99mTc-P was in the order: GalN not equal to CCl4 greater than ANIT, and the degree of decrease in the hepatic uptake ratio of 99mTc-P was in the order: GalN not equal to CCl4 greater than ANIT. These results suggest that the disorder in the hepatocytes may be one of causes for inducing the decrease in the hepatic uptake of 99mTc-P, and the consequence of this decrease may induce the decrease in the blood clearance of 99mTc-P.

Ｉｂｏｐａｍｉｎｅの臨床薬理 Ｉ 日本人健常成人における１回および反復経口投与時の安全性および薬理作用

Clinicopharmacological study of ibopamine, a new dopaminergic agent, was conducted in 11 Japanese healthy male volunteers. The safety and the pharmacological actions of the drug were assessed by single and multiple oral administrations.In single-dose study, 25, 50, 100 and 200mg of ibopamine were administered to 6 subjects 100mg of ibopamine was administered three times a day for 1 wk to 5 subjects in multiple dose study.Two subjects dropped out during the multiple-dose study because of the increased serum GPT in one case and decreased platelet count in another case.The rise of serum GPT seemed due to drug effect. However, the fall of platelet count did not seem due to drug effect because the case was diagnosed by a later examination as having idiopathic thrombopenia.The serum GPT values increased slightly in 2 other cases (up to 45, 46 KU/ml) but they did not drop out from the study.ECG examination revealed supraventricular premature contractions in a subject during single-dose study and in another subject during multiple-dose study.No abnormality was noted in subjective symptoms, body temperature, and body weight in both single- and multiple-dose studies.Blood pressure and pulse rate did not change significantly in both studies.ETc, which was assessed by mechanocardiography, showed a tendency to be shortened after single administration of ibopamine.Serum prolactin decreased after single administration of ibopamine.Diuretic and natriuretic effects were not evident after ibopamine administration.Urinary excretion of epinephrine, but not of norepinephrine and dopamine, increased significantly after drug administration. The mechanism of these changes remains to be clarified in future studies.

Environmental exposure to cadmium and effects on human health. Part 3. The results of blood examinations and blood pressure in inhabitants of the cadmium-polluted Jinzu river basin in Toyama Prefecture

Blood biochemical analyses and the measurement of blood pressure were carried out in 86 female inhabitants of a cadmium-polluted area aged 55 to 71 years. The values for their urinary β2-microglobulin (β2-m) ranged from 0.5 to 137.7mg/g creatinine with a geometric mean of 7.6mg/g creatinine. Therefore, the subjects were. divided into four groups according to the concentration of β2-m in urine: group I, 30mg/g creatinine (n=16).1) Red-cell count, hemoglobin concentration and hematocrit value in group IV significantly decreased compared to the other 3 groups.2) The GOT, GPT and γ-GTP activities in serum were in the normal range in all subjects. No significant differences among the 4 groups were detected in the results of serum total-protein concentration and protein analysis.3) In group IV, the mean values for serum creatinine and β2-m were significantly elevated compared to the other 3 groups. In contrast, serum uric acid concentrations decreased with increasing urinary β2-m.4) No significant differences were detected in the levels of serum Na, K, and Cl of the 4 groups. However, fractional sodium and potassium excretions were raised in group IV compared to the other 3 groups. Systolic and diastolic blood-pressure levels in group IV were the lowest among the 4 groups. Excessive renal sodium excretion due to renal tubular dysfunction may reduce the blood-pressure.

Effects of total parenteral nutrition with nucleoside and nucleotide mixture on D-galactosamine-induced liver injury in rats.

The effect of a nucleoside-nucleotide mixture on liver injury of rats induced by D-galactosamine was studied by examining changes in function and histopathology of the liver. Animals with liver damage received total parenteral nutrition with glucose and amino acids supplemented with a nucleoside-nucleotide mixture containing inosine, cytidine, GMP, uridine and thymidine, or with uridine which inhibits galactosamine injury, or with liver cell extract containing flavin adenine dinucleotide and nucleic acid derivatives. As control, animals with liver damage received total parenteral nutrition with glucose and amino acids only. The serum GOT and GPT concentrations were significantly lower in the group supplemented with nucleoside-nucleotide mixture than those in other groups. A large dose (1.2 g/kg) of uridine inhibited liver injury, but a lower dose (0.14 g/kg) did not have any effect, whereas nucleoside-nucleotide mixture containing the same amount of uridine inhibited the injury. Liver cell extract also did not improve liver function. Thus infusion of a physiological and balanced mixture of nucleosides or nucleotides may improve liver function in rats with liver injury.

Significance of activation of reticuloendothelial function after hepatectomy in cirrhotic rats.

Effect of hepatectomy on the prognosis of cirrhotic rats prepared by oral administration of thioacetamide was studied from the standpoint of the reticuloendothelial function and energy metabolism of the liver. OK-432, a streptococcal preparation, was used to activate reticuloendothelial functions. Administration of OK-432 to cirrhotic rats prior to 70% hepatectomy significantly prevented the elevation of serum GOT, GPT and LDH, the prolongation of blood coagulation and the decrease of serum complement level. Hepatic ATP synthesis and RNA content were significantly increase by the use of OK-432. These findings suggest that activation of reticuloendothelial functions at the time of massive hepatectomy in cirrhotic rats may diminish hepatic injury, maintain serum complement level, and improve protein synthesis of the liver.

Enhancement by glutathione depletion of ethanol-induced acute hepatotoxicity in vitro and in vivo

Ethanol at initial concentrations between 0.75 and 6 g/l produced a dose-dependent release of the enzymes glutamic-pyruvic-transaminase and sorbitol dehydrogenase (GPT, SDH) from the isolated perfused rat liver. At the concentration of 6 g/l, it also decreased the oxygen consumption and elevated the calcium content of the isolated livers. These toxic effects of ethanol were significantly enhanced in livers, the glutathione content of which had been depleted by pretreatment with phorone. Ethanol-induced toxicity in glutathione-depleted isolated livers could be prevented both by inhibition of alcohol dehydrogenase with 4-methylpyrazole and of xanthine oxidase with allopurinol. In rats, in vivo, 1.6 g/kg ethanol injected intravenously produced a small increase in serum GPT and SDH concentrations 4 h after its administration. This increase in enzyme activities was several-fold higher and longer lasting in rats pretreated with phorone. Glutathione depletion per se did not induce hepatotoxicity in vitro or in vivo. Since glutathione is involved in several lines of defense against oxidative damage, our results of an enhanced susceptibility of glutathione-depleted livers to ethanol toxicity favour the hypothesis that ethanol exerts its hepatotoxic action via an activation of molecular oxygen.

Effects of buthionine sulfoximine and cysteine on the hepatotoxicity of butylated hydroxytoluene in rats

Pretreatment with buthionine sulfoximine (BSO; 900 mg/kg) induced the elevation of serum GOT and GPT activities in a non-toxic dose of butylated hydroxytoluene (BHT; 250–500 mg/kg) in rats. The elevation of serum enzyme activities was accompanied by a remarked depletion of the hepatic glutathione (GSH) concentration. In contrast, pretreatment with cysteine (100–200 mg/kg) inhibited the elevation of serum enzyme activities at a toxic dose of BHT (1000 mg/kg). The effects of BSO and cysteine on BHT-induced hepatotoxicity in rats are discussed.