Serum Glutathione S-transferase Activity Research Articles

Addition of Butyric Acid and Lauric Acid Glycerides in Nursery Pig Feed to Replace Conventional Growth Promoters.

(1) Background: This study determined whether adding butyric acid and lauric acid glycerides in nursing pigs' feed would improve growth performance, proteinogram, biochemical parameters, and antioxidant status. (2) Methods: Ninety male pigs were divided into five groups with six repetitions per group: NC, negative control (no additive); TRI-BUT, addition of tributyrin in the basal ration; MDT-BUT, addition of mono-, di-, and triglycerides of butyric acid in the basal feed; MDT-LAU, the addition of mono-, di-, and triglycerides of lauric acid in the basal feed; and PC, positive control (addition of gentamicin in the basal feed). (3) Results: PC, TRI-BUT, and MDT-LAU resulted in a high average daily WG from days 1 to 39 (p < 0.01). MDT-LAU, MDT-BUT, and PC resulted in a greater feed:gain from days 1 to 39 than the NC (p = 0.03). Great concentrations of the gamma globulin fraction in all groups were observed than in the NC (p = 0.01). Ceruloplasmin, haptoglobin, and C-reactive protein concentrations were lower in all groups than in the NC (p < 0.05). Higher serum glutathione S-transferase activity was observed in the TRI-BUT and MDT-BUT than in the PC (p = 0.04). (4) Conclusions: The addition of butyric acid and lauric acid glycerides in the diet of pigs in the nursery phase can replace growth promoters since the products improve the growth performance, reduce acute-phase proteins, and increase gamma globulin concentrations.

Laying hens fed mycotoxin-contaminated feed produced by Fusarium fungi (T-2 toxin and fumonisin B1) and Saccharomyces cerevisiae lysate: Impacts on poultry health, productive efficiency, and egg quality

Mycotoxins represent substantial challenges to the farming industry. These include toxins produced by Fusarium fungi, particularly trichothecenes (toxin T-2) and fumonisin (FB1). In the present study, we determined the effects of addition on Saccharomyces cerevisiae lysate (SCL) added to feed contaminated with T-2 and FB1 in terms of health, productive efficiency, and egg laying quality. We used 60 Hy-line Brown laying hens, and divided them into five groups with four repetitions per group and three birds per repetition. There was one group with no contamination with toxin (NoC). The four other groups included combinations of mycotoxin (4 ppm T-2, and 20 ppm FB1): A contamination group was used as control (the C+ group), and another two contained 500 g/ton of SCL (Detoxa Plus®) (the C + D500 group) or 1000 g/ton of SCL (the C + D1000 group). Finally, one group received feed containing 500 g/ton of Detoxa Plus® and 1000 g/ton of Uniwall® MOS 25 (the C + D500 + U1000 group). The experimental period was 84 days, divided into three productive cycles of 28 days each. The NoC hens had greater egg production than the other groups. Hens that consumed feed with SCL had greater egg production than did the C+ group. The NoC hens produced eggs with greater weights than did the C hens; however, C + D1000 and C + D500 + U1000 birds produced greater egg weights than did the C+ group. The C+ group produced lower egg masses than did the NoC and C + D500 + U1000 groups. The feed intake (FI) was lower in hens that ingested mycotoxin. The use of SCL in feed minimized the negative effects of mycotoxin on feed conversion ratio (FI/dozen). Effects of treatment were detected for feed conversion ratio (kg/kg). The hens that consumed mycotoxin had lower shell resistance and thickness compared to those in the NoC group. The red color of egg yolk was greater in the control groups. There were fluctuations in levels of liver enzymes when birds consumed mycotoxin (sometimes reduced and sometimes increased); nevertheless, the cumulative effect increased the activity of alanine aminotransferase. The serum concentration of reactive oxygen species was greater in hens that ingested mycotoxin only on d 84 compared to the NoC group. Serum glutathione S-transferase activity was greater on d 56 in C + D500 and C + D1000 hens than in the others. We conclude that, in general, the consumption of mycotoxin impaired the performance and quality of the eggs of the hens; the addition of the S. cerevisiae lysate and the addition organic acids, yeast cell wall and mineral carrier minimized some of the negative effects caused by T-2 and FB1.

Role of Anthocleista vogelii in serum antioxidant defence system in cadmium-induced oxidative stress in Wistar rats

BackgroundCadmium (Cd) toxicity, which runs across the food chain, is chiefly regulated by in vivo antioxidant defence system or through antioxidant supplementation of biological systems predisposed to this environmental stressor. The present study was designed to examine the role of Anthocleista vogelii leaves in Cd-induced oxidative stress in the serum of Wistar rats through the application of response surface methodology (RSM) and biomonitoring of selective responses: malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), glutathione-s-transferase (GST) and peroxidase (POD) activities, respectively. The cold macerated plant leaves were subjected to fractionation process using methanol-hexane-chloroform (3:2:1 v/v) solvent system such that n-hexane fraction with ample antioxidant levels in terms of total phenolic content (TPC) and total flavonoid content (TFC) among others at p < 0.05 was selected for the study. The study employed central composite design (CCD) with twenty experimental “runs” of male Wistar rats for twenty-eight days, following a week of acclimatization, where n-hexane fraction of A. vogelii (NFAV), cadmium chloride (CdCl2) and body weights of rats were considered input factors in the study.ResultsThe study generated five quadratic models, which differed significantly at p < 0.05 for MDA levels as well as CAT, SOD, GST and POD activities in the sera of Wistar rats. The study revealed that exposure to Cd toxicity caused a marked increase (p < 0.05) in serum MDA levels, but a significant inhibition (p < 0.05) of serum SOD, CAT, GST and POD activities. However, Cd interaction with NFAV showed marked amelioration of Cd-induced oxidative stress, which was confirmed by significant decrease in serum MDA levels, but significant increase in serum SOD, CAT, GST and POD activities at p < 0.05 via the response surface plots. The study also confirmed the reliability and adequacy of the models for accurate prediction of the responses since R-squared (R2) values obtained were greater than 90%.ConclusionIt was inferred from the present study that the adequacy of the models validated the potency of A. vogelii leaves graphically in the amelioration of Cd-induced oxidative stress in the serum of Wistar rats. Hence, the plant was considered a rich source of bioactive compounds with significant antioxidant properties.

Phytogenic as feed additive for suckling dairy calves’ has a beneficial effect on animal health and performance

Abstract: The aim of this study was to evaluate whether the use phytogenic as feed additive of Holstein calves could exert beneficial effects on animal health and performance. Thirty newborn calves were randomly divided into two groups (control and treated), and the treated consisted of 10 g of the phytogenic product diluted in milk once a day for 30 days. Blood and fecal samples were collected, and fecal score was performed daily in order to determine the occurrence of diarrhea. Treated calves showed higher hematocrit on days 45 and 60 of life. Serum levels of urea, total proteins, globulins and glucose were lower in the treated group on day 60 of life, while triglycerides were lower on days 15 and 60 of life. Serum glutathione S-transferase activity was higher in treated animals on day 60 of life. Fecal bacterial count was lower in treated animals on days 30 and 60 of life. The weight gain was higher in treated animals on days 60 and 210 of life. Based on these results, it is possible to conclude that the addition of phytogenic as feed additive for calves was able to minimize fecal bacterial infections and to increase body weight gain.

Physiological changes in the adenosine deaminase activity, antioxidant and inflammatory parameters in pregnant cows and at post‐partum

The aim of this study was to evaluate the behaviour of adenosine deaminase (ADA) activity, as well as its participation in the immunomodulation of pregnant cows. Thus, sixteen cows were divided into two groups (A and B): the group A was composed by cows not pregnant (n=8), while the group B was composed by pregnant cows (n=8). Serum levels of interleukin-10 (IL-10), IL-6, tumour necrosis factor alpha (TNF-α), reactive oxygen species (ROS) and C-reactive protein (CRP), as well as ADA and glutathione S-transferase (GST) activities, were measured on five sampling times (3, 5, 7 and 8months of gestation, and soon after calving). Serum ADA activity was similar throughout the experiment in the cows belonging to the group A, but its activity increased during the experiment in cows from the group B, that is it was lower in the third and fifth months of pregnancy, and higher on months 7, 8 and after calving when compared to the group A. TNF-α and IL-6 serum levels were lower in pregnant cows compared to non-pregnant animals; however, they significantly increased after calving. Serum levels of IL-10 increased after 8months of gestation, but it reduced after calving when compared to the group A, while CRP increased on month 8 of gestation and after calving compared to the group A. Pregnant cows showed lower serum ROS levels on months 3, 5 and 7 of gestation, and higher levels at the post-partum. Serum GST activity was higher on month 5 of gestation in pregnant cows, but it was lower on months 7, 8 and in the post-partum compared to the group A. Based on these evidence, we concluded that ADA activity and the others mediators or inflammatory modulators have important role in the maintenance of cow's gestation due to their immunomodulatory effects.

Consumption of Soymilk Reduces Lipid Peroxidation But May Lower Micronutrient Status in Apparently Healthy Individuals.

Consumption of soy products is speculated to reduce the risk and progression of some disease conditions. The underlying mechanisms mediating this effect are uncertain, but the lowering of oxidative stress has been suggested. This study was aimed at investigating the effect of soymilk on antioxidant status and lipid peroxidation in apparently healthy individuals. Five hundred milliliters of soymilk was taken daily by each of 39 apparently healthy individuals for a period of 28 days. Two sets of blood samples (baseline and after 28 days of soymilk intake) were collected and assayed for total antioxidant capacity (TAC), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione S-transferase (GST), manganese (Mn) and zinc (Zn) levels, using standard methods. Consumption of soymilk significantly increased serum TAC and reduced serum MDA when compared with baseline values (P < .001, P < .001 respectively). The decrease in MDA concentration was significantly contributed by the women (P < .001). Mean serum Mn was also significantly reduced (P = .03) when compared with baseline values. There were no changes in serum Zn concentration and the activity of SOD enzyme. The serum GST activity was significantly increased in men (P = .02) and significantly reduced in women (P < .001) in comparison with their corresponding baseline values. Daily consumption of soymilk enhanced antioxidant status and this led to reduced lipid peroxidation. It also resulted in a significant reduction of Mn. The dietary use of soymilk as an adjuvant to supplement meals seems beneficial health wise. However, soymilk should be taken with caution as it could result in micronutrient deficiency.

Role of Glutathione S-Transferase in Coronary Artery Disease Patients with and Without Type 2 Diabetes Mellitus.

Glutathione S - transferase (GST) is an important enzyme in detoxification and helps in lowering oxidative stress. It is speculated that this enzyme is induced under conditions of oxidative stress as a protective mechanism. To evaluate the status of Glutathione S-transferase in Coronary artery disease patients with and without type 2 Diabetes mellitus. The study was conducted in the Department of Biotechnology, Swami Satyanand College of Management and Technology in collaboration with Department of Biochemistry, Govt Medical College Amritsar. A total of 133 diagnosed cases of Coronary Artery Disease (CAD) were selected from the OPD and Medicine Ward of a private hospital, Amritsar. CAD patients were segregated into two groups i.e., group-1 and group-2 on the basis if they had Type 2 Diabetes mellitus or not. A total of 110 ages and sex matched healthy individuals were taken as controls from the general population. Written informed consent was obtained from all the subjects. All the subjects were investigated for serum GST activity, Total antioxidant status, plasma GSH levels, serum MDA and lipid profile. Serum GST activity was significantly high (p<0.05) in CAD patients as compared to controls. CAD patients having Type 2 Diabetes had more raised serum GST activity, indicating marked oxidative stress in these patients. This was supported from the observation that serum MDA levels were also significantly (p<0.05) high in CAD patients with Type 2 Diabetes mellitus. Total antioxidant status was significantly depressed (p<0.05) in CAD patients whether diabetic or non-diabetic as compared to controls. No significant difference (p>0.05) in plasma GSH levels were observed between CAD patients and controls. Age and sex related variations in serum GST activity were insignificant (p>0.05). Increased serum GST activity in CAD patients especially with Type 2 Diabetes is suggestive of a protective mechanism to combat increased oxidative stress which was reflected by raised serum MDA level and depressed total antioxidant status in patient group. However, whether this effect is a short term or long term, a separate follow up study is required.

The Impact of Senile Cataract Maturity on Blood Oxidative Stress Markers and Glutathione-Dependent Antioxidants: Relations with Lens Variables

The Impact of Senile Cataract Maturity on Blood Oxidative Stress Markers and Glutathione-Dependent Antioxidants: Relations with Lens VariablesOxidative stress is implicated in senile cataract (SC) genesis, although the impact of SC maturity on blood oxidative stress markers is unclear. Total hydroperoxides, malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione S-transferase (GST) were measured in the blood and lens samples of patients having either immature (n=31) or mature SC (n=50), and in 22 blood samples from noncataract controls. Compared to controls, SC patients had higher plasma MDA and serum GST, and decreased plasma GR and GSH levels. Plasma GPx as well as hydroperoxides differed from control values only in patients with mature SC. The multivariate logistic regression analysis showed that the fall of plasma GR activity (OR 5.14; CI 1.82-14.51;p=0.0020), as well as serum GST activity (OR 3.84; CI 1.36-10.83;p=0.0108) were independently associated with the maturity of SC. Lens hydroperoxides, MDA and GST, showed no correlation with correspondent blood values, in contrast to GPx (r=0.715; p&lt;0.001) and GR (r=0.703; p&lt;0.001). This study showed that the severity of SC is associated with increased systemic oxidative stress, which could be due to the fall of GSH-dependent antioxidant enzymes activities.

Determination of Reduced Glutathione and Glutathione S-transferase of Poultry Birds Exposed to Permethrin Insecticide

<b> </b>The experiment was carried out to determine the effect of a permethrin insecticide on reduced Glutathione (GSH) and Glutathione S-transferase (GST) activity in the liver and serum of poultry birds. Six weeks old poultry birds (broilers) weighing between 400-600 g, divided into four groups of five birds each. The poultry birds were exposed for 30 days to different concentrations (1, 5 and 10%) of a locally manufactured insect powder called ‘Rambo’ which contains 0.6% permethrin. The control group had no insecticide added to their feed. The levels of reduced glutathione in the treated groups were significantly higher than those in the control group (p<0.05) in both the serum and liver of the poultry birds. Liver and serum Glutathione S-transferase activity was significantly lower (p<0.05) in 1, 5 and 10% insecticide concentrations as against the control. The total liver protein was significantly higher at all levels of pesticide exposure compared with the control while serum protein content was significantly higher at 5 and 10% insecticide concentrations. Results of this experiment confirmed the use of GST as a biomarker in ecological evaluation of environmental pollutants.

Analysis of serum glutathione S-transferase and urinary 8-hydroxy-2-deoxyguanosine in coke oven workers

To investigate the application of serum glutathione S-transferase (GST) and urinary 8-hydroxy-2-deoxyguanosine (8-OHdG) as the monitoring biomarkers for coke oven workers exposed to polycyclic aromatic hydrocarbons (PAHs). 47 male coke oven workers and 31 male control workers were investigated. Urinary 8-OHdG and serum GST were analyzed using high performance liquid chromatography (HPLC) with electrochemical detection and test kit. Urinary 1-hydroxypyrene (1-OHP) as internal exposure of PAHs was also determined simultaneously by alkaline hydrolysis and HPLC. The values of urinary 1-OHP, serum GST and urinary 8-OHdG were reported as median with interquartile range (P(25)-P(75)). Urinary 1-OHP [5.7 (1.4-12.0) micromol/mol Cr], serum GST [22.1 (14.9-31.2) U/ml], and urinary 8-OHdG [1.9 (1.4-15.4) micromol/mol Cr] in coke oven workers were significantly higher than in control workers [3.0 (0.5-6.4) micromol/mol Cr (P < 0.05), 13.1 (9.5-16.7) U/ml (P < 0.01), and 1.3 (1.0-4.0) micromol/mol Cr (P < 0.05) respectively]. Categorizing by smoking status, significant differences in urinary 1-OHP and serum GST were found only in smokers among coke oven workers compared to control workers (P < 0.01), and 8-OHdG levels only in non-smokers (P < 0.01). Additionally, there was significant correlation between urinary 1-OHP and serum GST activity (r(s) = 0.31, P < 0.01, n = 78). The multiple logistic regression analysis showed that coke oven workers were at the higher risk of having GST activities above 16.7 U/ml (OR = 13.2) and 8-OHdG levels above 1.8 micromol/mol creatinine (OR = 4.4). High body mass index was an independent factor to affect urinary 8-OHdG levels. The elevated serum GST activities and increased oxidative DNA damage were found in the coke oven workers. Occupational exposure and smoking interact on each other. Serum GST may be used as a biomarker for assessing the exposure of PAHs. Assay of urinary 8-OHdG may be useful for evaluating the risk of lung cancer in coke oven workers.

Different change patterns of the isozymes of cytochrome P450 and glutathione S-transferases in chemically induced liver damage in rat.

In this experiment, we studied the different changes in activities and protein levels of each subform of hepatic cytochrome P450 and glutathione S-transferase (GST), in chemical-induced liver injury in rats. Rats were administered 1,1-dichloroethylene (DCE), allyl alcohol (AA), bromobenzene (BB) and N,N-dimethylformamide (DMF) p.o. once every two days for 7 times, and decapitated 18 hr after the last administration. DCE and AA showed stronger hepatic toxicity than BB and DMF, as serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were higher in DCE and AA treated rats than in BB and DMF groups. Anti-cytochrome P450 inhibitable activity of toluene metabolism and/or immunoblot analysis showed that CYP2E1 and CYP2B1/2 were induced by BB and DMF, but not by the other two chemicals; CYP2C11 was greatly decreased by all of the four toxicants; and CYP1A1/2 was slightly reduced by the four treatments. These changes were reflected in testosterone metabolism. Formation of 6 beta- and 7 alpha-hydroxytestosterone from testosterone was enhanced only in DMF-treated rats, whereas that of 2 alpha- and 16 alpha-hydroxytestosterone was reduced by all of the four chemicals. Serum GST activity was increased only in BB and DMF treated rats, but liver cytosolic GST activity was enhanced by all of the four hepatotoxicants, with higher values in BB and DMF groups than in DCE and AA groups. Immunoblot analysis demonstrated that GST Yp was induced by BB and DMF treatments, and Ya and Yc were increased only by BB. GST Yk and Yb1 were not affected by the treatments. The different change patterns of enzymes by a specific toxin and the similar modifying effect on a specific enzyme by different toxins were discussed in relation to the liver damage and to the heterogeneous distribution of enzymes in liver.

Modification of ricin and its hepatotoxicity and activity against hepatocellular cancer in mice.

AIM:To observe the effects of ricin (RT) with and without chemical modification on both hepatotoxicity of mice and activity against hepatocellular cancer (HCC), and evaluate the possibility to improve RT anticancer activity via chemical modification.METHODS:RT was modified with N-succinimidyl3(2-pyridyldithio) propionate (SPDP),a heterobifunctional cross-linker, and SPDP derivative of RT (PDP-R) was obtained.The serum glutathione-s-transferase (SGST) activity,as an index of liver damage, was determined in mice intoxicated with RT and PDP-R,at various doses and time.The tissue damage of HCC in the nude mice ip injected with PDP-R was compared with that with RT at the same dose by immunohistochemical method, the relative content of both RT and PDP-R in the HCC tissues was measured by computerized image-analysis. RESULTS:The SGST activities increased with doses or/and time intoxicated with both RT and PDP-R, and the increase in the value of RT group was more significant than that in the PDP-R group; the SGST activity of RT group was 2.8-fold (P < 0.01) of PDP-R group at a dose of 12.5&mgr;g/kg for 42h, showing the much lower toxicity of R-PDP than that of RT. Under an optical microscope, hemolysis and necrosis of massive cells in the HCC tissues of PDP-R group were observed and the ratio of necrosis mounted to 90.5% while the corresponding value of RT group only to 62.5%.With computerized image-analysis, the average relative content of RT and PDP-R in the HCC tissues,represented as greyness, was 140.06 plus minus 3.43 and 169.10 plus minus 2.74, respectively. There was significant difference between the two (P< 0.05), indicating the higher content of PDP-R in the HCC tissue than that of RT.CONCLUSION:The hepatotoxicity of PDP-R to mice may be reduced by chemical modification with SPDP, but both the affinity of PDP-R to the HCC tissues and ability to kill it may be stronger than that of RT. So this might be a valuable attempt to improve the anticancer activity of RT.

Carbon tetrachloride-induced alterations in hepatic glutathione and ascorbic acid contents in mice fed a diet containing ascorbate esters.

The effects of L-ascorbyl stearate and L-ascorbyl palmitate on carbon tetrachloride-induced alterations in glutathione and ascorbic acid content in mouse livers were investigated. Powdered food containing 1% ascorbate ester was given to mice for 3 days before and 1 day after a single injection of CCl4 (0.1 ml/kg, i.p.). Biochemical parameters were determined 1 day after the CCl4 administration. The ascorbate esters markedly attenuated CCl4-induced alterations such as reductions in ascorbate content and hepatic glutathione S-transferase (GST) activity, and increases in glutathione and calcium content and serum GST activity. The CCl4-induced rise in thiobarbituric acid-reactive substances, an index of lipid peroxidation, was not affected by ascorbate feeding. These findings suggest that exogenous ascorbate, in addition to endogenous glutathione, is available to maintain the intracellular milieu in a reduced state, and that this system operates more effectively in aqueous compartments than in membrane lipid bilayers.

Alteration of hepatic glutathione S-transferases and release into serum after treatment with bromobenzene, carbon tetrachloride, or N-nitrosodimethylamine

The effects of bromobenzene, carbon tetrachloride, and N-nitrosodimethylamine (DMN) on hepatic glutathione S-transferase activity were studied in untreated and in phenobarbital- or ethanoltreated. rats. In phenobarbital-treated rats, the isozymic composition of the hepatic cytosolic glutathione S-transferases was changed after giving hepatotoxic chemicals; glutathione S-transferases 2-2(AA), 3-3(A), 1-2(B), 3-4(C), and 4-4 + 5-5(D+E) were present in cytosol from control rats, but only glutathione S-transferases cochromatographing with transferases 4-4 + 5-5(D+E) were detected in rats given carbon tetrachloride or bromobenzene. A marked decrease in hepatic and an increase in serum glutathione S-transferase activity were also observed after carbon tetrachloride or bromobenzene treatment, but little change was seen after giving DMN. On the contrary, in untreated or ethanol-treated rats. DMN administration decreased hepatic glutathione S-transferase activity and caused an elevation in serum glutathione S-transferase activity. The isozymic composition of the hepatic cytosolic glutathione S-transferases after giving DMN to untreated rats was also altered, but the alteration was much less than that observed after giving carbon tetrachloride or bromobenzene to phenobarbital-treated rats. The elevation in serum glutathione S-transferase activity was accompanied by an increase in both serum glutamate-pyruvate transaminase activity and serum bilirubin concentrations. Thus, hepatic glutathione S-transferase activity was altered and released into serum after giving hepatotoxic chemicals, and the alteration in glutathione S-transferase activity was dependent on treatment with phenobarbital or ethanol.

Chloroform-induced alteration of glutathione s-transferase activity

The effect of chloroform treatment on the hepatic glutathione S-transferases was studied in phenobarbital-treated rats. The apparent isozymic composition of glutathione S-transferases in hepatic cytosol was changed after chloroform treatment. Glutathione S-transferases AA, A, B, C, and D + E were observed in hepatic cytosol from untreated rats; in contrast, the catalytic activity associated with basic glutathione S-transferases, such as AA, A, B, and C, decreased with time after chloroform treatment. Glutathione S-transferase B was not detectable 2 hr after chloroform treatment, and glutathione S-transferases AA and C were scarcely detectable after 5 hr. Twenty-four hours after chloroform treatment, glutathione S-transferases A and C were clearly detectable as was D + E and a small amount of B. Hepatic cytosolic glutathione S-transferase activity was decreased by chloroform treatment, and reached a minimum at 5 hr after treatment. Corresponding to the decrease of hepatic cytosol glutathione S-transferase activity, serum glutathione S-transferase activity was elevated maximally 5 hr after chloroform treatment and returned to almost normal by 24 hr. Treatment of rats with SKF 525-A or cysteine inhibited the chloroform-induced elevation of serum glutathione S-transferase activity. The chromatographic properties of the gluathione S-transferases present in serum were similar to glutathione S-transferase D + E. Furthermore, after incubation of partially purified cytosolic glutathione S-transferases with chloroform in the presence of hepatic microsomes and NADPH, only transferase D + E was detected. The addition of bilirubin to partially purified cytosolic glutathione S-transferase decreased the basic character of glutathione S-transferases B and C. In conclusion, chloroform caused a release of hepatic cytosolic glutathione S-transferases into serum. Both the active metabolite of chloroform, which was produced by the microsomal cytochrome P-450 system, and bilirubin, which was increased by chloroform treatment, played roles in altering the properties of the glutathione S-transferases.

Serum glutathione S-transferase in experimental liver damage in rats.

The changes of serum glutathione S-transferase (GST) was observed after carbon tetrachloride (CCl4) administration to Wistar rats. Serum GST activity increased rapidly and reached the peak 24 hours after CCl4 administration, and decreased rapidly thereafter. Centrilobular massive necrosis was already observed at the peak time of serum GST activity. On the other hand, serum glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) activities varied slowly, and the peak time of GOT and GPT activities was 36 hours after CCl4 administration. GST-containing Y fraction obtained from rat liver was injected intravenously to control and nephrectomized rats, and the plasma disappearance of GST activity was observed. The plasma disappearance of GST activity was very rapid in the control rats. When the Y fraction obtained from 1/12 g liver was injected, no statistically significant difference in the plasma GST half lives was observed between the control and nephrectomized rats. Half life of serum GST was significantly shorter in control rats receiving the Y fraction from 1/60 g liver, comparing with that in nephrectomized rats receiving the same amount of Y fraction. From these results, serum GST is concluded to be a precise index of the early stage of hepatic necrosis in the rat, and considerable amount of GST is excreted from the kidneys, but most of the enzyme is metabolized in vivo.

Serum glutathione s-transferase activity in liver diseases

Assay conditions of human liver glutathione S-transferase and its activity in human serum from liver disease patients were investigated. One mmol/l reduced glutathione, and 1 mmol/l 1-chloro-2,4-dinitrobenzene, pH 6.5, were used for the measurement, because of the very low non-enzymatic conjugation. Glutathione S-transferase activity was inhibited by bilirubin, but this inhibition was counteracted by the presence of a low concentration of albumin. The normal human serum glutathione S-transferase activity was 5.2 ± 2.4 I.U./l (mean ± S.D.), and was not influenced by any differences of age, sex or leukocyte count. A significant increase in serum enzyme activity was noted in cases of acute hepatitis with GPT exceeding 200 I.U./l, primary hepatoma and metastatic liver cancer. Some of the cases with fulminant hepatitis showed extremely high values. The degree of correlation between serum glutathione S-transferase and GOT or GPT was high in acute hepatitis, with GOT or GPT exceeding 200 I.U./l, in fulminant hepatitis, primary hepatoma and gall stones, while in chronic hepatitis and liver cirrhosis it was low. In cases of acute hepatitis and fulminant hepatitis, the disappearance of serum glutathione S-transferase from the blood was much faster than that of GOT and GPT. Serum glutathione S-transferase measurements will provide new and unique information for the diagnosis of acute liver diseases.