Elevated Serum Enzyme Activities Research Articles

Assessment of the usefulness of macroenzyme determination in the situation of increased plasma enzyme activity in the absence of clinical symptoms

Introduction: The increased activity of serum enzymes is usually a reason of multiple, often expensive and invasive diagnostic procedures. However, there are situations in which abnormal enzyme activity persists for many months or years, and detailed studies do not confirm the existence of anatomic disease. Such is the case when enzymes form complexes with immunoglobulins on the basis of the immune antigen-antibody reaction. This phenomenon is usually benign condition, is transient and does not require treatment. Aim of study: Detection of the macroenzymes in patients with elevated serum enzyme activity. Evaluation of the relationship between the presence of macroenzymes and the age of patients, body mass index, lipid profile, chronic and autoimmune diseases. Material and methods: Macroenzymes were examined by polyethylene glycol precipitation (PEG) in 121 patients with elevated values of liver or pancreatic enzymes. Results: In the study group, a statistically significant difference was found comparing the BMI of men and women. BMI was significantly higher in men with macroenzymes (p = 0.006). It was shown that the BMI of people with serum macroenzymes is significantly higher (p = 0.049) than those without macroenzymes. A statistically significant correlation was observed between the presence of macroamylase and body weight, r = 0.33, p = 0.039. A positive correlation of triglycerides and macrogenzofacts in the serum was found. Macroamylase was observed the most frequently in the healthy group and those suffering from chronic diseases (45.83% and 42.86%). In the group of autoimmune diseases (autos) the most common was macro-GGTP (42.86%). In patients with inflammatory bowel disease, 80% of the confirmed macroenzymes in serum were macro-CK.

Biochemical and histopathological study in rats intoxicated with carbontetrachloride and treated with camel milk

The unique characters of camel’s milk make it used extensively in the field of medicine as anti-microbial, anti-diabetic and hepatoprotective agent. The lack of studies demonstrating the protective effect of camel’s milk against hepatotoxic compound was the main reason beyond the conduction of the current experiment which aimed to investigate the protective effects of camel’s milk against carbontetrachloride (CCl4) induced hepatotoxicity. Therefore, 24 rats were fed on standard diet and divided into four groups. Rats of the first group and second groups were injected i/p with paraffin oil and received either tap water (control 1) or camel’s milk (control 2), respectively. Rats of the third and fourth groups were injected i/p with CCl4 and received either tap water or camel’s milk, respectively. At the end of the experiment (5 weeks), blood and liver samples were collected for biochemical and histopathological analysis. The present findings revealed that, CCl4 elevated serum enzyme activities of liver and some biochemical parameters, but these effects were prevented by the treatment of rats with camel milk. Histopathologically, a great amount of mononuclear cells infiltration, necrotic cells and few fibroblasts were observed in liver of CCl4 treated group. The present study concluded that camel milk treatment may play a protective role against CCl4-induced liver damages in rats. These protective effects were in the form of improving of liver enzyme activities, blood biochemical parameters and histological picture of liver of intoxicated rats. In the future, examination of the liver protective effect of camel milk against CCl4 in dose dependant manner could be investigated.

Changes in the haemato-biochemical pattern due to experimentally induced haemonchosis in Sahabadi sheep

The study evaluated the damage caused by Haemonchus contortus in terms of blood loss, faecal clearance of plasma protein and elevated serum enzyme activity in Sahabadi sheep. Apparently healthy Sahabadi sheep (n=15) were selected randomly based on phenotypic characteristics and divided into two groups; infected (n=8) and uninfected control (n=6) and one sheep was used as donor animal. Each animal of infected group were orally infected with 700 third stage larvae (L3) of H. contortus/kg body weight. Blood from all the fourteen animals were collected at weekly intervals starting from day one to 42day post infection. Parameters studied were haemoglobin concentration (Hb), packed cell volume (PCV), total erythrocyte count (TEC), total serum protein, serum albumin, serum globulin, alkaline phosphatase, Alanine amino transferase and Aspartate amino transferase. Statistical analysis showed that significant decreases in Hb, PCV, TEC and serum protein concentration and significant increases in serum enzymes level in infected sheep compared to uninfected control. The present study concluded that experimental H. contortus infection caused disturbances to the haemopoietic system resulting anaemia and severe damage to abomasal mucosa resulting lower serum protein and higher enzyme activities.

Protective effect of Panax ginseng against serum biochemical changes and apoptosis in liver of rats treated with carbon tetrachloride (CCl 4)

The purpose of this study was to investigate possible beneficial effects of Panax ginseng (PG) on carbon tetrachloride (CCl 4)-induced acute hepatotoxicity in rats. CCl 4 challenge elevated serum enzyme activities of liver and some biochemical parameters, but these effects were prevented by the pretreatment of rats with PG. Histologically, a great amount of mononuclear cells infiltration, necrotic cells and few fibroblasts were observed in liver of CCl 4 group. Also, CD68 + and caspase-3 staining cells were diffused in both lobular and portal areas. However, PG pretreatment had a little influence on the number of caspase-3 immunpositive staining cells in the liver, but CD68 + staining areas were significantly decreased in the PG + CCl 4 when compared to CCl 4 group. We conclude that PG treatment may play a protective role by enhancing liver enzyme activities and recovering biochemical parameters, and improving the changes in histological structure against CCl 4-induced liver damages in rats.

Effect of Clarias gariepinus cultured in contaminated water on rats

In this study, African Catfish (Clarias gariepinus) were cultured in water contaminated with phthalate, benzene and cyclohexane (10 microg/mL), respectively, over a period of 65 days. They were, thereafter, used as protein source to formulate feed for albino rats (Wistar strain) for 28 days. The weights of the body and selected tissues of the rats were monitored and standard enzyme assays were conducted for some enzymes in the serum. Results showed that rats in cyclohexane group gained 58% whereas the control group gained 46% of body weight. Liver weight (absolute and relative) of test rats were found to be significantly lower than that of control (p < .05). Enzyme activity of serum of test rats was found to be significantly higher than that of control (p < .05). Experimental evidence suggests leakage of enzymes from the liver to the serum, thus the elevated serum enzyme activity and that the contaminants may damage the liver.

In vitro and in vivo evaluation of a melamine dendrimer as a vehicle for drug delivery

Cell-based and acute and subchronic in vivo toxicity profiles of a dendrimer based on melamine reveal that this class of molecules warrants additional study as vehicles for drug delivery. In cell culture, a substantial decrease in viability was observed at 0.1 mg/mL. For the acute studies, mice were administered 2.5, 10, 40 and 160 mg/kg of dendrimer via i.p. injection. At 160 mg/kg, 100% mortality was seen 6–12 h after injection. For the other cohorts, blood chemistry work revealed no renal damage was taking place at 48 h. Liver enzyme activity nearly doubled for the mice treated at 40 mg/kg suggesting hepatotoxicity. For the subchronic studies, three i.p. injections of 2.5–40 mg/kg of dendrimers were administered at 3-week intervals. No mortality was observed. Forty-eight hours following the last administration, blood chemistry revealed no renal damage, but liver damage was indicated by elevated serum enzyme activity at the highest dose. Histopathological data further confirms that doses up to 10 mg/kg show no hepatic damage at subchronic doses. However, subchronic doses at 40 mg/kg lead to extensive liver necrosis.

Release of mitochondrial rather than cytosolic enzymes during liver regeneration in ethanol-intoxicated rats

Background Partial hepatectomy (PH) promoted rapid increase in serum of hepatic enzyme activities localized in mitochondria preferentially to increase enzyme activities from cytosol; low doses of ethanol (EtOH) administered to PH rats expedited return to normality of these elevated serum enzyme activities. The fate of released mitochondrial enzymes from liver was investigated in this study to advance knowledge of the role of mitochondria during priming phase of liver regeneration. Methods Catalytic activity of mitochondrial and cytosolic proteins was measured in remnant liver after PH and in elutes of perfused remnant livers from control and ethanol-intoxicated rats. Results During the first 24 h of liver regeneration (LR), mitochondrial enzymes—glutamate dehydrogenase, aspartate amino transferase, and malate dehydrogenase—diminished 33–58% in mitochondria, increased 17% in cytosol, and for two enzymes rose 68–86% in perfusates. Cytosolic lactate dehydrogenase decreased transiently in cytosol (24%) and increased only 13% in perfusates. Activity of cyclooxygenase I (mitochondrial membrane-attached enzymes) was not modified. Ethanol intoxication after PH produced earlier and slightly higher extrusion of matrix mitochondrial enzyme activities. Conclusions Selective increase of mitochondrial membrane permeability appeared as an important event during priming phase of LR after PH, thus sustaining preferential release of mitochondrial proteins outside the organelle in comparison with limited redistribution of cytosolic and mitochondrial membrane proteins. High doses of EtOH delayed LR and re-enforced mobilization of proteins produced by PH probably by enhancing greater mitochondrial membrane permeability.

Effects of acetylbergenin against [formula omitted] -galactosamine-induced hepatotoxicity in rats

The hepatoprotective effects of acetylbergenin were examined against D -galactosamine (GalN)-induced liver damage in rats, compared with that of bergenin reported previously. Acetylbergenin was synthesized from acetylation of bergenin, isolated from Mallotus japonicus, to increase lipophilic and physiological activities. Acetylbergenin was administered orally once daily for 7 days and then GalN (400 mg kg−1, i.p.) was injected at 24 h and 96 h after the final administration of acetylbergenin. Acetylbergenin reduced the elevated serum enzyme activities of alanine/aspartate aminotransferase, sorbitol dehydrogenase and γ -glutamyltransferase and the formation of hepatic malondialdehyde induced by GalN. Acetylbergenin also significantly restored towards normalization the decreased levels of glutathione and the decreased activities of glutathione S-transferase and glutathione reductase induced by GalN. Therefore, these results suggest that acetylbergenin has hepatoprotective effects against GalN-induced hepatotoxicity by inhibiting lipid peroxidation and maintaining an adequate level of GSH for the detoxification of xenobiotics as underlying hepatoprotective mechanisms. In addition, lipophilic acetylbergenin showed more activity in the hepatoprotection than that of the much less lipophilic bergenin reported previously.

Comparative Carcinogenicity in Sprague-Dawley Rats of the Polychlorinated Biphenyl Mixtures Aroclors 1016, 1242, 1254, and 1260

A comprehensive chronic toxicity and carcinogenicity study was conducted on a series of Aroclors (1016, 1242, 1254, and 1260). Each Aroclor was assessed at multiple dietary concentrations, ranging from 25 to 200 ppm, for 24 months in male and female Sprague-Dawley rats. Liver toxicity was indicated by elevated serum enzyme activity (AST, ALT, and GGT), elevated serum cholesterol concentration, decreases in hematologic parameters (RBC, Hb, and Hct), hepatocellular hypertrophy, an increased incidence of altered hepatocellular foci, and an increased incidence of hepatocellular neoplasms (primarily adenomas). Liver toxicity was distinctly more severe in females than in males. The incidence of hepatocellular neoplasms was highly sex-dependent (females > males), differed between Aroclor mixtures and, for females, increased with dose and followed the general incidence pattern of Aroclor 1254 > Aroclor 1260 ≈ Aroclor 1242 > Aroclor 1016. A significant response (p < 0.05) in males was seen only for the high dose of Aroclor 1260. A small increase in the incidence of thyroid gland follicular cell adenomas was noted in males for Aroclors 1242, 1254, and 1260, with the incidence being uniform across dose groups and Aroclor mixtures. For females, increased survival relative to controls was observed for all Aroclor treatment groups. A significantly decreased trend in the incidence of mammary gland neoplasms compared to control was also noted for females receiving Aroclors 1242, 1254, and 1260.

High inflammatory activity is associated with an increased amount of IFN-gamma transcripts in peripheral blood cells of patients with chronic hepatitis C virus infection.

The mechanisms underlying the chronic hepatic inflammatory process in hepatitis C virus (HCV) infection are not well understood. Some models of experimentally induced hepatitis point to a role of interferon-gamma (IFN-gamma) secreted by liver-infiltrating peripheral blood lymphocytes (PBMC) in mediating hepatocellular injury. In the present study, IFN-gamma gene expression was analysed in PBMC and in liver biopsy specimens from patients with chronic HCV infection using a quantitative reverse transcriptase polymerase chain reaction technique. IFN-gamma gene expression by PBMC from HCV-infected patients exhibiting elevated serum transaminase activities was found to be increased up to ninefold when compared with (1) healthy individuals, (2) HCV-infected patients exhibiting normal or only slightly elevated serum enzyme activities, or (3) patients with drug-induced elevated serum transaminase activity. A histo-pathological evaluation of liver biopsy sections revealed further that high IFN-gamma gene expression by PBMC was associated with a more pronounced degree of inflammatory activity. In individual patients, the expression of IFN-gamma by PBMC was shown to parallel closely serum transaminase activities during IFN-alpha 2a therapy. Moreover, liver biopsy material from patients chronically infected with HCV contained higher amounts of IFN-gamma transcripts than liver tissue from patients with liver disorders unrelated to HCV infection or without any liver disease. These data thus demonstrate a close association between the amount of IFN-gamma transcripts in PBMC and in liver tissue and the inflammatory activity in chronic HCV infection in man.

Plasticity of response to equal quantities of endurance training separated by non-training in humans

1. 1. The pattern of elevation of several serum biochemical indices (BI) of training stress (creatine kinase, CK; lactate dehydrogenase, LDH; aspartate aminotransferase, AST, Ca 2+; urate, UR; urea, U; total protein, Prot; cholesterol, C) were measured serially through two extended periods of training, including taper (50 days each) separated by a period of complete non-training (90 days) in two male subjects. 2. 2. The patterns of variation in BI were compared with similar variation in elements of a two compartment model predicting performance from training. 3. 3. These elements arbitrarily described as Fitness [ g( t)] and Fatigue [ h( t)] were estimated daily from a daily training impulse [ w( t)] defined from the duration time and heart rate elevation of an individual in a training session. 4. 4. g( t) and h( t) were used to predict performance [ p( t)] which might be expected from the training undertaken. So that: p( t) = k 1 g( t) — k 2 h( t) where k 1 and k 2 are arbitrary constants. 5. 5. Performance p( t) when iteratively modelled against a Criterion running Performance, Cp( t) measured serially throughout training, over a standard distance, then defines the pattern of variation in the elements g( t) and h( t) (Morton et al., 1990). 6. 6. Hard training for 28 days and a succeeding 22 days of taper in each training period produced a rise and fall in elevated serum enzyme activity, ESEA, (CK, LDH and AST) which mirrored the time-course pattern of h( t), the fatigue element of the dose/response model of training, with a slight phase delay. 7. 7. Thus ESEA was already declining during hard training. 8. 8. During the taper period ESEA declined rapidly to base line. This response was remarkably symmetrical in each, separate training period. 9. 9. The Criterion running performance (CP) declined during hard training and rebounded throughout the taper period reaching an asymptote before beginning to decline again as training fitness [ g( t)] was lost, although the fatigue [ h( t)] state was now minimal. 10. 10. Serum Prot, U, Ur respectively were also elevated throughout hard training, first following the hypothesized h( t) curve but showing a biphasic response, declining during the latter phase of hard training, and rising again during taper. 11. 11. The symmetry of response of these indices in each period was less evident than the ESEA response. None of the BI patterns measured was in phase with g( t), all, seemingly, reflected the catabolic rather than the anabolic process of hard training.

Cardiovascular and muscular strain during a tree planting season among British Columbia silviculture workers

Cardiovascular and muscle strain were determined in 16 British Columbia reforestation workers during a period of tree planting (75 days). Serial data collected from each worker included pre- and post-work blood chemistry on the first day of the work shift; working heart rate (HR), a PWC170 fitness test, and a daily diary of an individual's work-rest schedule. Repeated blood samples from each planter were analysed for the elevated serum enzyme activities (ESEA) of creatine kinase (CK), lactate dehydrogenase (LDH), and aspartate transaminase (AST), and for the blood haematology parameters (BH) of haematocrit (Hct), red blood cell count (RBC), and haemoglobin (Hgb). HR and BH were used as an index of cardiovascular strain and ESEA was used as an index for musculoskeletal strain. A group mean working heart rate of 116.5 +/- 9 b.min-1 (range 100.0-139.1) was sustained throughout the period of an 8.0 hour day representing 39.2% of the delta Heart Rate ratio (ratio of elevated working Hr above resting to maximum HR). Grouped data were analysed by sample day for a subset of planters (n = 10) participating in six sample dates during the first 32 days of planting. Pre- and post-work ESEA were significantly higher throughout the entire planting period when compared with a pre-season resting control group (n = 9, p < or = 0.01). The post-work rise in CK and AST from pre-work values decreased during successive weeks of work as some adaptation to the work rate occurred. LDH continued to rise and was significantly elevated on day 32 compared with day 1. No significance was found in the BH variables between sample dates, yet a decreasing trend was observed. However, pooled data from all subjects for all sample dates showed a highly significant difference (p < or = 0.01) between pre- and post-work samples for both ESEA and BH. ESEA increased and BH decreased. These data present evidence that the work rate and rest time of a tree planter are not well ordered within the daily and seasonal working routine, and may compromise worker well-being in the silviculture industry.

Elevated serum enzyme activity: an explanation-based model.

The well-documented pattern of elevated serum enzyme activity (ESEA) data after a single bout of unaccustomed exercise can very easily be modeled using a biexponential curve. However, the changed pattern of ESEA after a second exercise bout, or after a period of conditioning or during repetitive training, demonstrates that exercise-induced adaptations have been taking place. The mechanism for this is unclear. One plausible explanatory hypothesis is that within the pool of muscle fibers, some fibers are stress susceptible or weak, and the pool becomes diminished as a result of damage induced by earlier exercise. Repair of the muscle damage takes place during the period after exercise but may be incomplete at the time of a subsequent exercise bout, in which case ESEA amplitude is reduced. Frequently repeated bouts may lead to chronic ESEA. These ideas are developed, both mathematically and graphically, by means of a compartment model approach. In so doing, the model explains documented patterns of ESEA response to single and multiple exercise bouts, both closely and widely spaced. Predictions are possible using the model, in particular the previously unreported baseline overshoot (reduction below resting levels) in serum enzyme activity occurring beyond 82 h after very severe exercise. Some directions for experimentation to test the validity of the model are suggested.

Glycogen debranching enzyme deficiency: Long‐term study of serum enzyme activities and clinical features

In glycogen storage disease type III (glycogen debranching enzyme (DE) deficiency), the activities of serum alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase may be strikingly elevated during childhood but are low during adult life. To determine the pattern of the elevated serum enzyme activities in relationship to diet, the biochemical subtype and clinical symptoms, 13 patients with DE deficiency were studied. Activities of serum aspartate and alanine transaminases, lactate dehydrogenase, and alkaline phosphatase were markedly elevated during infancy. Continued elevation of enzyme activities during childhood appeared to be related to DE deficiency in liver, but unrelated to DE deficiency in muscle. Activity elevations correlated inconsistently with diet and poorly with childhood growth rate or the presence of hypoglycaemia. The serum enzyme activities declined around puberty concomitantly with a decrease in liver size. Although periportal fibrosis and micronodular cirrhosis indicated the presence of hepatocellular damage during childhood, the decline in serum enzyme activities with age and the absence of overt hepatic dysfunction suggest that the fibrotic process may not always progress.

Dose/response effects of exercise modeled from training: physical and biochemical measures.

This study has measured the pattern of elevated serum enzyme activity (ESEA) during extended daily training in a dose-response manner and compared ESEA to the pattern of accumulated fitness and fatigue predicted from a mathematical model previously described. Blood samples were taken regularly during the study from each subject and the activity of lactate dehydrogenase (LDH), creatine kinase (CK), and aspartate aminotransferase (AST) in the serum was measured. Although no single physiological/biochemical correlate of the hypothesized fatigue compartment of performance is firmly identified it is significant that the pattern of variation of model fatigue and ESEA throughout training were similar although slightly out of phase. With continued hard training, model fatigue began to plateau and concomitantly ESEA declined exponentially from its initial high value in early training. During relative rest throughout a tapering period following training both ESEA and fatigue reverted quickly towards baseline and follow the similar but earlier time course in blood of a degradative membrane enzyme phospholipase A2 observed in clinical studies.

Ursodeoxycholic acid for the treatment of primary sclerosing cholangitis: A 30-month pilot study

We investigated the effects of once-daily oral administration of 10 mg/kg ursodeoxycholic acid (generic name, ursodiol) on elevated serum enzyme activities, bilirubin, cholesterol, bile acids and symptoms in patients with primary sclerosing cholangitis. A 30-mo, open-label, pilot trial was designed to cover four periods: (a) 3 mo of pretreatment observation (period 1), (b) 6 mo on ursodiol (period 2), (c) 3 mo withdrawal of treatment (period 3) and (d) 18 mo of extended retreatment (period 4). Diagnosis was confirmed by cholangiography and liver biopsy specimens. We enrolled 12 patients with persistently elevated pretreatment alkaline phosphatase and gamma-glutamyltransferase levels (at least twice the upper limit of normal), and observed them for a median of 37 mo. Significant reductions in serum total cholesterol levels and in serum enzyme activities indicating cholestasis and hepatocellular injury occurred during ursodiol treatment in both treatment periods 2 and 4 and relapsed with treatment interruption in period 3. Elevated serum bilirubin and symptoms of disabling fatigue, pruritus and diarrhea were improved by ursodiol. Improvements have continued after 2 yr of treatment in 10 patients (1 patient had a transplantation after he relapsed on withdrawal of ursodiol therapy; another died of postoperative complications of colon resection for carcinoma). No other cases of clinical deterioration were observed in the retreatment period. The longer term reductions of alkaline phosphatase, transaminases, bilirubin and cholesterol after 2 yr of treatment were even greater than the initial reductions after 6 mo of treatment. These results justify initiation of larger, controlled clinical trials, with serial morphological evaluations of the liver and biliary tree.

Effect of exercise on serum enzyme activities in humans.

Increased serum enzyme activity after exercise was first reported in 1958; subsequent studies have established that many factors determine the degree to which the serum activities of a variety of enzymes increase during and after exercise. The serum activities of those enzymes found especially in muscle, particularly creatine kinase, increase in proportion to the intensity and duration of the preceding exercise, peaking 24 hours after exercise; the effect of duration is dominant, so that the highest postexercise serum enzyme activities are found after very prolonged competitive exercise such as ultradistance marathon running or triathlon events. Weight-bearing exercises which include eccentric muscular contractions such as bench stepping and downhill running induce the greatest increases in serum enzyme activities; serum enzyme activities increase very little even after prolonged participation in those non-weight-bearing activities such as swimming and cycling which do not include eccentric muscular contractions. Prolonged (greater than 2 hours) daily training or competition in weight-bearing activities produces chronically elevated serum enzyme activities. Serum enzyme activities increase more with exercise in males, Blacks and the untrained than they do in females, Whites and the trained, respectively; age does not appear to influence the degree to which serum enzyme activities increase with exercise. There is a remarkable individual variability in the degree to which serum enzyme activities increase with exercise; a 50-fold difference in post-race serum creatine kinase activities has been found in healthy and equally trained athletes completing the same 90km ultramarathon footrace. The biochemical explanation for this degree of individual variability is not currently understood; possibly persons who show abnormally large increases in serum enzyme activities with exercise may have as yet unrecognised subclinical myopathies. No circadian rhythms have been identified for serum enzyme activities; activities rise during the day because of increased physical activity. The rise in serum enzyme activities is greater after exercise at altitude or in the heat than after equivalent exercise at sea level or in the cold. The most likely explanation for the increased serum enzyme activities that follow prolonged weight-bearing activities that also cause marked muscle soreness, is myofibrillar damage in particular sarcomeric Z-disk disruption.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of methyl (+) (3S)-1,2,3,4-tetrahydro-3-hydroxymethyl-beta-carboline-2- carbodithioate(THC), a new hepatoprotective agent, on protein synthesis and chronic liver injury induced by carbon tetrachroride in rats.

The effects of oral administration of methyl (+) (3S)-1,2,3,4-tetrahydro-3-hydroxymethyl-beta-carboline-2-carbodithioa te (THC) on protein synthesis in the liver and chronic liver injury induced by carbon tetrachloride (CCl4) in rats were studied. THC increased liver weight and the contents of protein and ribonucleic acid, but not deoxyribonucleic acid, in the liver. THC also accelerated the 14C-leucine incorporation into hepatic microsomal and cytosol proteins in rats when the animals were treated with THC 24 h before sacrifice. In addition, when the animals were treated with THC during the latter half of a 5 weeks CCl4-treatment period, THC had a marked therapeutic effect on CCl4-induced chronic liver injury in rats by an improvement of the decreased body weight gain, suppression of the elevated serum enzyme activities (glutamic pyruvic transaminase, glutamic oxaloacetic transaminase and alkaline phosphatase) and increases in the decreased serum total protein and glucose contents. In the liver, THC also improved the decreased protein content, the increased triglyceride content and histopathological changes. These results suggested that THC stimulates protein synthesis in the liver and has a therapeutic effect on chronic liver injury induced by CCl4.

Elevated serum galactosylhydroxylysyl glucosyltransferase, a collagen synthesis marker, in fibrosing lung diseases

The activity of galactosylhydroxylysyl glucosyltransferase, an enzyme catalyzing collagen biosynthesis, was measured in the sera of 101 patients with various pulmonary diseases to study whether detectable enzyme amounts are liberated into the serum from the lung tissue, and whether this is associated with the development of lung fibrosis. Increased serum galactosylhydroxylysyl glucosyltransferase activity was found in all the patients with progressive pulmonary fibrosis and in about half of the patients with acute stages of farmer's lung and infectious pneumonia. In one third of the patients with stage I sarcoidosis the serum enzyme activity was slightly increased, whereas in bronchial asthma and chronic bronchitis the values were mostly within the normal range. In conclusion, elevated serum enzyme activity was demonstrated in connection with those respiratory diseases in which pulmonary fibrosis was already verifiable or relatively often develops later. Measurements of serum galactosylhydroxylysyl glucosyltransferase may, thus, be useful in evaluating actual lung collagen synthesis in human pulmonary diseases.

Mixed-function oxidase system induction and propylene hepatotoxicity.

Propylene is hepatotoxic to male Charles River COBS Sprague-Dawley rats pretreated with polychlorinated biphenyls (PCB: Aroclor 1254). Four-hour inhalation exposure to 50,000 ppm propylene increased liver weight/body weight ratios and elevated serum enzyme activities in PCB-pretreated animals. Hepatic microsomal cytochrome P-450 content of PCB-pretreated rats dropped profoundly during propylene exposure and remained depressed for at least 24 h. In addition, PCB-pretreated, propylene-exposed rats exhibited a decrease in the specific activity of hepatic microsomal aniline hydroxylase. However, there was no change in activities of either hepatic microsomal aminopyrine demethylase or glucose-6-phosphatase. Propylene exposure of rats pretreated with beta-naphthoflavone (BNF), phenobarbital (PB), or a mixture of BNF and PB was not hepatotoxic. However, there was, in these animals, a substantial decline in hepatic microsomal cytochrome P-450 levels 24 h after the start of propylene exposure. Hence, the propylene-dependent process resulting in hepatic cytochrome P-450 destruction is qualitatively or quantitatively different from the process that causes acute hepatotoxicity. Preexposure fasting had no effect on the hepatotoxicity resulting from a 4-h exposure of PCB-pretreated rats to 50,000 ppm propylene. Administration of SKF-525A to PCB-pretreated rats immediately prior to propylene exposure completely prevented elevations in serum enzyme activities and liver weight/body weight ratios. In vitro incubation of hepatic microsomes prepared from either BNF-, PB-, or PCB-pretreated rats with an atmosphere of 20% propylene/80% air produced in NADPH-dependent decrease in cytochrome P-450 content. These results suggest that PCB pretreatment is a prerequisite for propylene hepatotoxicity in the rat. Cytochrome P-450-dependent bioactivation of propylene is associated with this hepatotoxicity, but further studies are needed to characterize the mechanism of the PCB-propylene interaction.