Induction of hepatitis in adult Syrian hamster by H-1 virus.

The induction of hepatitis in adult hamster by H-1 virus was documented by demonstrating an increase in serum SGOT and SGPT at 3-9 wk postinoculation. The electrophoresis pattern of LDH isoenzymes showed a marked increase in the liver fraction (fraction 5) indicating liver damage in infected hamsters. The pathology displayed in diseased livers revealed a focal degeneration of hepatic cells although infiltration of white cells was not observed. H-1 virus is apparently capable of producing hepatitis (without symptoms) in adult hamsters as well as cause hepatitis and severe cerebral disease in newborn hamsters.     

Low activity of gamma-glutamyl transpeptidase in serum of acute intrahepatic cholestasis.

Low gamma-glutamyl transpeptidase (gamma-GTP) activity in serum was observed in 11 patients with acute intrahepatic cholestasis (cholestatic hepatitis and fulminant hepatitis), despite a marked increase in bilirubin levels. Inhibitors of gamma-GTP were not detected in sera of these patients. Their gamma-GTP levels in the liver were significantly higher than those in chronic liver diseases. An electrophoretic study of liver gamma-GTP in acute intrahepatic cholestasis showed the same mobility as in chronic liver diseases. These results suggest that the low serum gamma-GTP activity in acute intrahepatic cholestasis is due to factors inhibiting the release of the enzyme from the liver.     

Plasma ornithine carbamyl transferase level as an indicator of ischaemic injury of rat liver

The activity of ornithine carbamyl transferase (OCT) and glutamate pyruvate transaminase (GPT) in serum has been correlated with the extent of necrosis 24 h after different periods of ischaemia in rat liver. The extent of necrosis has been quantified as the volume density of necrosis in the total ischaemic liver lobes using tetranitro BT. The GPT-activity in serum is maximal between 1 and 5 h after different periods of ischaemia, whereas OCT reaches its maximum between 5 and 12 h after ischaemia. The total amount of leaked enzyme-activity as well as the peak value give a linear correlation with the extent of necrosis for OCT and GPT. There is a difference between the character of these two enzymes in that a small leakage of GPT does not indicate liver cell necrosis later on. However, the appearance of OCT in the blood, an enzyme localized in the mitochondrial matrix, has a predictive value for the extent of necrosis, likely to occur later on. GPT, an enzyme from the cytoplasm, can also occur in the blood during the reversible stage of liver cell damage.     

Liver function tests during amoebic liver abscess formation in indomethacin-treated hamsters

Establishment of Entamoeba histolytica infection is facilitated through macrophage effector disruption by a prostaglandin E2 (PGE2)-mediated mechanism. Infection severity may be measured by weight of abscess formed. Indomethacin (Indo) treatment of infected hamsters reduced abscess weight by 30% at 7 days post-infection presumably by inhibition of PGE2. To explain reductions in abscess development by Indo treatment, we determined liver functionality in Indo-treated or untreated animals, either healthy or infected. Determinations of serum glutamic oxaloacetic (SGOT) and glutamic pyruvic (SGPT) transaminases, serum alkaline phosphatase (SAP), total serum protein (TSP), and bilirubinemia were done. SGOT, SGPT, and SAP activities showed a significant increase in their values by 600% at seven days post-infection in infected animals in both conditions; nonstatistical differences were found between animals treated or not. This increase did not correlate with the percentage of damage. Infected nontreated hamsters showed TSP levels 30% below normal group (P < 0.05). Infected Indo-treated hamsters had no significant differences compared to normal values. Infected nontreated animals showed an increase in bilirubin, particularly in indirect bilirubin, whereas infected Indo-treated hamsters showed total bilirubin values lower than normals (P < 0.05), with a decrease in direct bilirubin levels. Our results demonstrated that E. histolytica infection in hamsters produces similar abnormalities in liver function as it does in humans, and that the beneficial effect of Indo treatment on amoebic abscess development is not related with an improvement of liver functionality.     

Assessment of protective role of polyherbal preparation, Livina, against anti-tubercular drug induced liver dysfunction

The present study evaluated the possible protective role of Livina (a polyherbal preparation) against anti-tubercular therapy (ATT)-induced liver dysfunction in patients of pulmonary tuberculosis. Patients were given intensive phase treatment with 4-drugs (rifampicin, INH, pyrazinamide and ethambutol) used for anti-tubercular therapy for 2 months, followed by a 4-month continuous phase treatment with 2 drugs (rifampicin and INH) under clinical advice and supervision. Both qualitative and quantitative measures of liver function were assessed, at different time intervals, before and after ATT. Analysis of data showed that the incidence of qualitative manifestations of liver dysfunction were greater in the placebo treated group as compared to the test drug group. None of the patients of either group showed clinical jaundice. Most signific changes ant were observed in the SGOT and SGPT levels in the placebo group, wherein the levels of both enzymes were higher at 4 and 8 weeks post-ATT, as compared to the respective baseline (0 week) values. When Livina (2 capsules twice daily) was given with ATT drugs, incidence of qualitative manifestation of liver dysfunction was insignificant and SGOT and SGPT levels were also significantly lower than the placebo+AITT drugs treated group. These results indicate that the test drug (Livina) was efficacious, against ATT-induced hepatic dysfunction in patients of pulmonary tuberculosis.     

Effect of Emblica officinalis (Gaertn) on CCl4 induced hepatic toxicity and DNA synthesis in Wistar rats

A single dose of CCl4 (1 ml/kg body weight, po in corn oil) increased the levels of SGOT (serum glutamate oxaloacetate transaminase), SGPT (serum glutamate pyruvate transaminase), LDH (lactate dehydrogenase), glutathione-S-transferase and depletion in reduced glutathione, glutathione peroxidase and glutathione reductase. It also caused enhancement in the levels of lipid peroxidation (LPO) and DNA synthesis. There was also pathological deterioration of hepatic tissue as evident from multivacuolated hepatocytes containing fat globules around central vein. The pretreatment of E. officinalis for 7 consecutive days showed a profound pathological protection to liver cell as depicted by univacuolated hepatocytes. Pretreatment with E. officinalis at doses of 100 and 200 mg/kg body weight, prior to CCl4 intoxication showed significant reduction in the levels of SGOT, SGPT, LDH, glutathione-S-transferase, LPO and DNA synthesis. There was also increase in reduced glutathione, glutathione peroxidase and glutathione reductase. The results suggest that E. officinalis inhibits hepatic toxicity in Wistar rats.     

Experimental cross infections of Fasciola hepatica in lambs and calves.

The effects of experimental infections with Fasciola hepatica of ovine and bovine origin in homologous and heterologous hosts and in uninfected controls were compared; groups comprised 5 animals each. The effects of the infections were monitored by biweekly determinations of packed cell volumes (PCV), serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), gamma glutamyl transpeptidase (GGT), serum iron, bilirubin levels, alkaline phosphatase (AlP) and total serum protein levels. Infected animals showed changes in SGOT, SGPT and GGT activity levels, and GGT activity levels, and infected lambs showed changes in PCV and AlP. However, no no significant differences in these serum levels between infected host groups were attributable to fluke strain. At necropsy, calves infected with ovine and bovine strains on an average had about the same number of flukes, but lambs infected with a high dose of the bovine strain on the average had nearly twice the number of flukes as those infected with ovine strain. Weight gains did not differ within host groups; liver damage was extensive in all infected animals. On the basis of these experiments, the pathogenicity of the ovine and the bovine strains of F. hepatica appears to be the same.     

Ocimum sanctum aqueous leaf extract provides protection against mercury induced toxicity in Swiss albino mice

HgCl2 (5.0 mg/kg body weight) induced toxicity led to significant elevation of lipid peroxidation (LPO) level but decline in the glutathione content in liver of Swiss albino mice. In serum of HgCl2 treated mice there was significant elevation in serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) activities but significant decline in the alkaline phosphatase activity. Animals treated with O. sanctum extract (10 mg/kg body weight, po) before and after mercury intoxication showed a significant decrease in LPO level, SGOT and SGPT activities and increase in serum alkaline phosphatase activity and glutathione (GSH) content. Ocimum treatment alone did not alter SGOT, SGPT and alkaline phosphatase activities but significantly enhanced reduced glutathione. The results suggest that oral administration of Ocimum extract provides protection against HgCl2 induced toxicity in Swiss albino mice.     

东当归对四氯化碳及乙醇性肝损伤的保护作用

研究东当归水提取物对四氯化碳及乙醇所致小鼠SGPT和SGOT活性升高的影响。在四氯化碳及乙醇所致小鼠急性肝损伤的血清中检测SGPT和SGOT值。结果表明,37．5％、75．0％和150．0％东当归水提物在体内显著抑制四氯化碳及乙醇所致小鼠SGPT值和／或SGOT值升高。东当归水提取物对小鼠四氯化碳及乙醇性肝损伤具有保护作用。     

The salubrious effect of tamaxifen on serum marker enzymes,glycoproteins, and lysosomal enzymes level in breast cancer women

Tumour markers correlate strongly with prognosis based on tumour burden and surgical resectability. If chemotherapy is extremely effective in certain stage of the disease, the sensitive marker may be of great use in monitoring disease response and drug treatment. Hence, this study was launched to evaluate the changes in tumour marker enzymes like lactate dehydrogenase (LDH), glumate oxaloacetate transaminase (SGOT), glutamate pyruvate transaminase (SGPT), alkaline phosphatase, and acid phosphatase in before and after 3 and 6 months tamoxifen treated breast cancer patients. In addition, the changes in serum glycoproteins viz., hexose, hexosamine, and sialic acid and lysosomal enzymes such as N-acetyl-beta-D-glucosaminidase, beta-D-galactosidase, and beta-D-glucuronidase were analysed in these patients. These values were compared with their age matched healthy control subjects. At 6 months evaluation, the tamoxifen treated postmenopausal breast cancer women showed a statistically significant decreased (p < 0.001, 0.05 respectively) levels of LDH, SGOT, SGPT, alkaline and acid phosphatases than their baseline values. Similarly, the levels of hexose, hexosamine, and sialic acid and N-acetyl-beta-D-glucosaminidase, beta-D-galactosidase, and beta-D-glucuronidase were decreased significantly (p < 0.001 ) in tamoxifen received postmenopausal women. The result of this study suggested that tamoxifen potentially retard the metastasis of breast cancer as well as the bone demineralisation in postmenopausal breast cancer women. Thus, tamoxifen may also have its antitumour activity through its beneficial effects on tumour marker enzymes and serum proteins in breast cancer women.     

Hepatoprotective effect of Hibiscus hispidissimus Griffith, ethanolic extract in paracetamol and CCl4 induced hepatotoxicity in Wistar rats

Hibiscus hispidissimus Griff. is used in tribal medicine of Kerala, the southern most state of India, to treat liver diseases. In the present study, the effect of the ethanolic extract of Hibiscus hispidissimus whole plant on paracetamol (PCM)-induced and carbon tetrachloride (CCl4)-induced liver damage in healthy Wistar albino rats was studied. The results showed that significant hepatoprotective effects were obtained against liver damage induced by PCM and CCl4 as evidenced by decreased levels of serum enzymes, glutamate oxaloacetate transaminase (SGOT), glutamate pyruvate transaminase (SGPT), serum alkaline phosphatase (SAKP), serum bilirubin (SB) and an almost normal histological architecture of the liver of the treated groups compared to the toxin controls. The extract also showed significant antilipid peroxidant effects in vitro, besides exhibiting significant activity in quenching 1, 1-diphenyl-2-picryl hydrazyl (DPPH) radical, indicating its potent antioxidant effects.     

The effect of iloprost and NDGA in ischemia reperfusion injury in rat liver.

In this study, the effects of iloprost (ZK 36374) and NDGA on warm ischemia and reperfusion injury in rat liver were investigated. Rats were given isotonic saline (control group), iloprost 25 micrograms/kg i.v. (group II) just before warm ischemia or NDGA 10 micrograms/kg i.v. (group III) 5 min before reperfusion or the same drugs were given together (group IV). Serum SGOT, SGPT, and LDH values and tissue malondialdehyde (MDA), glutathione (GSH), prostaglandin (PG)E2, and leukotriene (LT)C4 levels were determined after ischemia-reperfusion injury. Histopathologic examination of the liver was carried out under the light microscope. The serum SGOT, SGPT and LDH levels improved significantly in groups II, III, and IV when compared with the control group (p < 0.05). There was a significant decrease (p < 0.05) in tissue MDA levels and significant increase (p < 0.05) in tissue GSH levels in group I, when compared with group IV and the control groups. The values did not differ significantly in group IV when compared to controls. The LTC4/PGE2 ratio was low and histologic findings were worse in group III. In conclusion, iloprost was found to be beneficial in preventing the ischemia-reperfusion injury in the rat livers. NDGA, either by direct toxic effect or by shifting the arachidonic acid metabolism to the cyclooxygenase route, was not found to be as effective. Iloprost and NDGA did not exert a synergist effect.     

Serum transaminases activity and histopathological changes in Clarias lazera chronically exposed to nitrite

Increase in serum transaminases (GOT and GPT) activity attributable to nitrite toxicity was observed in juvenile Clarias lazera after chronic exposure to nitrite. The application of SGOT and SGPT assays for monitoring the effect of nitrite exposure over a 6-month period has shown that changes in activities are correlated with histological effects in Clarias liver. Kidneys from fish exposed to nitrite were not noticeably different histologically from that of control fish. Hypertrophy and hyperplasia were the most consistent lesions that occurred in the gills. Lifting of lamellar epithelium and necrosis of some epithelial cells were also prominent.     

Short Term Training Attenuates Opening of the Mitochondrial Permeability Transition Pore Without Affecting Myocardial Function Following Ischemia-Reperfusion

Hepatotoxicity is one of the most serious adverse effects of antituberculosis drugs. The aim of this study was to produce a rat model of isoniazid-rifampicin (INH-RIF) induced hepatotoxicity. Materials and Methods: Wistar rats (100–150 g) were treated with different doses of INH i.e. 25, 50 and 75 mg/kg/day with a fixed dose of RIF i.e. 50 mg/kg/day intragastrically for a period of 28 days. Serum glutamate oxaloacetate aminotransferase (SGOT), glutamate pyruvate aminotransferase (SGPT), bilirubin (Bil) and alkaline phosphatase (ALP) were estimated at 0,14, 21 and 28 days in rats. Histological analysis was carried out to assess the liver. Results: Treatment of rats with INH–RIF (50 mg/kg/day each) induced hepatotoxicity as judged by elevated serum SGPT, SGOT, Bil and ALP as compared with their base line. Histological evaluation of INH–RIF induced hepatotoxicity also showed liver damage. Conclusion: The present study suggests that 50 mg/kg/day each of INH–RIF was selected as hepatotoxic dose (i.e. minimum dose with maximum hepatotoxicity) in wistar rats.     

Serum constituents of Suncus murinus

Blood samples were collected by cardiac puncture from nine-week-old suncus, mice and rats those had been fasted for 16 hours, and the serum was assayed for the levels of corticosterone, cortisol, and other constituents. The following results were obtained: The serum levels of corticosterone and cortisol and corticosterone/cortisol ratio of suncus were about the same as those of human. The SGPT, gamma-GT, ALP, LDH, Ca and K values in suncus were all within the normal range of the respective values in human. SGOT, amylase, BUN, Na, Cl, Fe and inorganic phosphate values were higher, and total cholesterol, triglyceride, phospholipid, creatinine, urea, total protein, albumin and bilirubin levels were lower in suncus than the respective normal values in human. The values of SGOT, amylase, ZTT, and K were higher in female than in male suncus, while the values of gamma-GT and ALP were higher in the male. Feeding the animals individually in the individual cages for a week increased the values of direct bilirubin, total cholesterol, ZTT, Na, K and Cl and lowered the value of urea. The values of SGPT, ALP and triglyceride of suncus obtained in 1984 were higher, the value of albumin was lower, than the respective values obtained in 1983. The value of cholinesterase in suncus was very small.     

Prediction of recurrence in giant cell bone tumors by DNA cytometry.

The most interesting therapeutic aspect of giant cell bone tumors is which patients can be cured without a risk of recurrence by intralesional surgery (curettage). To find out the suitability of some DNA cytometric and morphometric parameters for showing differences between this group of patients (n = 9) and those with recurrence (n = 12), the parameters mean ploidy, 2cDI (mean square deviation of the tumor cell DNA content from the normal 2c value), mean nuclear area and its variability were calculated from cytologic specimens prepared by a cell separation technique from formalin-fixed, paraffin-embedded tissues, measuring the values of 100 stromal cells per case by a TV image analysis system. Further measurements were performed on 19 cases of different diseases of the bone and on an additional 17 cases of giant cell tumors without follow-up. The 2cDI allowed us to distinguish the two groups of patients, with and without recurrence, without overlap; even the lowest value for patients with recurrence was higher than the highest value for cured ones. Mean ploidy analysis resulted in a less convincing discrimination of the patients. Mean nuclear area and its variability failed to predict recurrence. Single-cell DNA cytometry provided a parameter, 2cDI, that was able to predict recurrence in patients with giant cell bone tumors with high sensitivity.     

长白山地区产18种根类药材对四氯化碳肝损伤的影响

目的 研究18种药材水提物对小鼠SGPT和SGOT的影响。方法 在四氯化碳所致小鼠急性肝损伤的血清中检测SGTP和SGOT值。结果 东当归、党参、莪术、北龙胆、茜草、黄芪、川芎和北柴胡水提物显著抑制四氯化碳所致小鼠SGTP和SGOT值升高。结论 东当归等8药材水提取对四氯化碳损伤具有保护作用。     

Purification and characterization of glutamate dehydrogenase as another isoprotein binding to the membrane of rough endoplasmic reticulum

Glutamate dehydrogenase (GDH) was purified from rough endoplasmic reticulum (RER) in rat liver using anion-exchange and affinity chromatography. As GDH has been known as an enzyme that exists mainly in the matrix of mitochondria, the properties of purified GDH were compared with those of mitochondrial GDH. The GDH activity in 0. 1% Triton X-100-treated RER subcellular fraction was nearly the same as intact RER, whereas that of the mitochondrial fraction increased by 50% after the detergent treatment. In kinetic values, in addition, mitochondrial GDH had a higher K(m) value for NADP(+) than NAD(+), whereas the K(m) value for NAD(+) was higher than that for NADP(+) in the case of GDH of RER, which showed a difference in specificity to cofactors. Moreover, when two GDH isoproteins were incubated at 42 degrees C or treated with trypsin, GDH from RER was more stable against heat inactivation and less susceptible to proteolysis than mitochondrial GDH in both cases. In addition, GDH of RER had at least five amino acids different from mitochondrial GDH when sequences of N-terminal and several internal peptide fragments were analyzed. These results showed that GDH of RER is another isoprotein of GDH, of whose properties are different from those of mitochondrial GDH.     

Proliferative response and renewal of hepatic function following cocaine administration in mice

Experiments were undertaken to investigate the hepatic, temporal and spatial sequence of events following a single injection of cocaine, a known hepatotoxin. Centrilobular necrosis was induced in male mice (DBA/2Ha) 24 hr post-injection (PI). The time course of hepatic damage was monitored by assaying microsomal cytochrome P450 content, the activity of microsomal FAD-containing monooxygenase (FAD-M) and by determining the levels of serum glutamic pyruvic transaminase (SGPT). Kinetics of the onset of DNA synthesis were determined by autoradiography of thin liver sections and the incorporation of 3H-methyl thymidine into perchloric-acid-precipitable material. There was no increase in the labelling index (LI) and thymidine (TdR) incorporation in the first 24 hr PI. The LI rose to 14.6% and TdR incorporation showed a 5-fold increase over control values 48 hr PI. Both indices declined slightly at 72 hr PI and returned to control values by 96 hr PI. In contrast, the cytochrome P450 content declined by 69%, the FAD-M activity dropped by 40% and the SGPT levels showed an 18-fold increase at 24 hr PI, coincident with cytological signs of necrosis. Although the patterns of recovery differed between these selected enzymes, normal values were attained by 96 hr PI. These results demonstrate that cell damage and hepatic dysfunction precede the onset of DNA synthesis and subsequent proliferation.