Hepatotoxicity and renal toxicity induced by gamma-radiation and the modulatory protective effect of Ficus carica in male albino rats.

It is well-known that gamma radiation initiates generation of free radicals which prompting serious cellular damages in biological systems. In the present study, we investigated the role of Ficus carica, a natural antioxidant substance, in modulating changes in liver and kidney functions, antioxidant enzyme's gene expression, and apoptosis, in male albino rats exposed to gamma radiation. A total of 40 rats were used in this experiment and divided equally into 4 groups: Group 1, rats administered distilled H2O (Control); Group 2, rats administered F. carica; Group 3, rats irradiated; and Group 4, rats treated with F. carica and irradiated. Groups 3 and 4 were exposed to whole-body gamma radiations at a dose level of 8 Gy and with a dose rate of 0.762 Gy/min. F. carica was administered to rats by gavage, for 3 consecutive weeks, before exposure to radiation. Five rats were sacrificed from each group at intervals of 24 and 72 h after cessation of treatment. The results revealed marked increases in alanine aminotransferase and aspartate aminotransferase levels in liver, a decrease in albumin level and increase in urea level in kidney. Irradiation resulted in cytotoxic effects as indicated by elevation in antioxidant enzyme's gene expression at 24 h, the opposite was observed at 72 h. Immunohistochemical analysis revealed that cytochrome c and p53 expressions significantly increased following exposure to radiation. Oral administration of F. carica pre-irradiation as a natural product plays a modulatory protective and anti-apoptotic role against cells damaged by free radicals induced by whole-body irradiation.

X-ray responses of human colon tumor cells grown in artificial capillary culture.

Clone A human colon adenocarcinoma cells were grown in three-dimensional artificial capillary culture (ACC) to determine responses of capillaries treated 3 weeks after tumor cell inoculation with a specific, easily quantifiable cytotoxic agent, ionizing radiation. The high-density growth of tumor cells in ACC can be considered to be an in vitro analogue of a solid tumor. Changes in extracapillary space (ECS) fluid concentrations of lactate dehydrogenase (LDH) and aspartate aminotransferase (GOT) and the utilization of glucose in circulating medium were monitored after a supralethal radiation dose (90 Gy) of X-rays. Immediately after irradiation, increased levels of LDH and GOT were found that reached maximum levels about four to five times those found in nonirradiated control capillaries at 10-13 days post irradiation and then declined. Patterns of enzyme production appeared to correlate with the numbers of nonviable tumor cells collected from the ECS of the artificial capillaries. In contrast, glucose utilization showed little correlation with either enzyme concentration or dead cell production. It was determined that, while capillaries grown and treated in this manner appear to respond in a dose-dependent manner to ionizing radiation (as indicated by changes in LDH and GOT levels), these particular end points are relatively insensitive and are not suitable for studies in which therapeutic levels of X-radiation might be given. In other studies, tumor cells were removed from unirradiated capillaries by trypsinization and used to obtain complete survival curves after graded doses of X-radiation. The dose-response curves obtained indicate that clone A colon tumor cells grown in ACC show a marked decrease in their ability to accumulate sublethal radiation injury as compared to responses of these cells growing exponentially in asynchronous monolayer cultures, to synchronized mid-G1 tumor cells, or to tumor cells in stationary growth phase. These data suggest that ACC is a potentially useful model to study the effects of cytotoxic agents on human tumor cells.

Increased serum enzyme activity in microwave-exposed rats.

Heat stable serum enzymes were studied in rats exposed to microwaves (2.45 GHz, 120 Hz amplitude modulated) 24 hr after a single 4-hr exposure or immediately after 3 and 10 exposures to 0.1 to 55 mW/cm2. In addition, stable colonic temperature at 41.5 degrees C for 30 min was maintained by microwave exposure in a group of five rats under barbiturate anesthesia. Alkaline phosphatase and lactic dehydrogenase did not increase as a result of microwave exposure. Increased serum glutamic pyruvic transaminase (GPT) and glutamic oxaloacetic transaminase (GOT) were noted in the 41.5 degrees C group 24 hr after exposure. A threshold body temperature for acute cellular injury after microwave exposure was demonstrated. The acute cellular injury could be in the liver. These mild elevations in the serum enzyme levels (mean +/- SE, GOT = 167 +/- 40 U/liter: GPT = 74 +/- 26 U/liter) indicated that the injuries were not accompanied by any significant sequelae in the rat. From this threshold and colonic temperature (41.5 degrees C for 30 min) in barbiturate-anesthetized, microwave-exposed rats, we derived a tentative threshold for the whole-body average absorption rate at 14 W/kg (70 mW/cm2 at 2.45 GHz for adult rats) for 4 hr. This tentative threshold is subject to changes by duration of exposure and by compounding variables influencing maintenance of body temperature.

[Photooxidation of aspartate transaminase from chicken heart cytosol]. / Fotookislenie aspartat-transaminazy iz tsitozolia serdtsa kur.

Rose-bengal-sensitized photooxidation of aspartate transaminase from chicken heart cytosol results in a loss of enzymatic activity which follow first order kinetics down to 70--75% inactivation. 0.9 Histidine, 0.9 tryptophane residues and 1.5 SH groups per enzyme subunit were found to be modified in the photooxidized transaminase, which retained 26% residual activity. Photodestruction of the coenzyme was about 16%. The rate of enzyme photoinactivation is constant in the pH range 6--8, and drastically decreases with lowering pH from 6 to 4. alpha-Ketoglutarate partially protects the holoenzyme from inactivation. The apoenzyme undergoes photoinactivation at a rate almost twice as rapid as the holoenzyme. Photooxidized apotransaminase retains affinity to pyridoxal phosphate and binds as much coenzyme as the native apoenzyme. Photooxidation induces no significant alterations in the circular dichroism pattern of the enzyme in the 200 to 240 nm range. However, positive circular dichroism is markedly increased in the absorption bands of aromatic amino acids (260--300 nm). The affinity of photooxidized holoenzyme for glutarate and alpha-methyl aspartate is greatly decreased. On the other hand, photooxidized enzyme retains its ability to bind alpha-alanine and to catalize the transamination half-reaction between alpha-alanine and the bound coenzyme. These findings imply that photooxidation disturbs the binding of the distal carboxyl group of dicarboxylic substrates. This may be due to a localized conformational change induced by destruction of a photoreactive histidine residue at the active site. A role of the histidine residue in transamination reaction is discussed.

[Effect of low-intensity pulse-modulated microwave on human blood aspartate aminotransferase activity]. / Issledovanie izmeneniia aktivnosti aspartataminotransferazy syvorotki krovi cheloveka pri nizkikh amplitudno-modulirovannykh SVCh EMI-vozdeistviiakh.

Pulse-modulated microwaves (frequency 2375 MHz, intensity: 2 microW/cm2 and 8 microW/cm2, pulse modulation from 50 to 390 Hz with step of 20 Hz; exposure time 5 min) changed the activity of aspartataminotranspherase of the donor blood. Aspartataminotranspherase activity was strongly dependent both on modulation frequency and microwave intensity. Maximum activity was found at 390 Hz and 8 microW/cm2. Maximum observed activity was about six times greater than control level of activity.

[The combined action of ionizing radiation and nitro compounds on the activity of the basic enzymes of glutamic acid metabolism]. / Sochetannoe vozdeistvie ioniziruiushchego izlucheniia i nitrosoedinenii na aktivnost' osnovnykh fermentov obmena glutaminovoi kisloty.

The activity of aspartate aminotransferase, glutamate dehydrogenase in the liver of rats in 1, 7 and 15 days after gamma irradiation effect of the dose of 0.5 Gy on the background of consumption by animals of sodium nitrate, sodium nitrite and nitrosodiethylamine was studied. The combined influence of chemical agents and gamma irradiation modified the effects of nitro compounds-xenobiotics on processes of the synthesis and dissociation of the glutamic acid as well as the intensity of transamination of the reamination by aspartate aminotransferase.

[Effect of electromagnetic fields on the living body. II. Changes in alanine and aspartate aminotransferase activities in subcellular fractions of the liver of guinea pigs]. / Wplyw pola elektrycznego na organizm zywy. Cz. II. Zachowanie sie aktywnosci aminotransferazy alaninowej i asparaginianowej we frakcjach subkomórkowych watroby swinek morskich.

The 50 Hz frequency electric field was applied to guinea pigs at different times of the day. The electric field effects upon the alanine and asparagine aminotransferase in supernatant, mitochondrial and nuclear fractions of guinea pig liver were observed. The highest increase in alanine aminotransferase activity was observed in the mitochondrial fraction, whereas asparagine transferase exhibited the highest activity increase in the supernatant fraction. Those changes may be indicative of adverse effects of electric field upon the liver cell metabolism.

[Effect of high frequency electromagnetic fields on the processes of transamination in the liver and small intestine tissues of rats]. / Izmenenie protsessov pereaminirovaniia v tkaniakh pecheni i tonkogo kishechnika krys pri deistvii vysokochastotnykh élektromagnitnykh polei.

The influence of electromagnetic waves of metrical and centimetrical range on the transaminoferases activity was studied in the liver and small intestine of 69 rats. The experiment shows that the activity of aspartate and alanine aminotransferases is dependent on the power and duration of the action. It is established that the action of both the short-wave 160 mA diathermy and 30 MW/cm2 microwaves for 20 min is accompanied by inhibition of the liver and small intestine aminotransferases activity. The 20 min action of 12 MW/cm2 microwaves induces an increase in the aminotransferases activity of the liver, small intestine and serum.

[Functional interrelationships between dehydrogenases and transaminases in various regions of the rat brain as affected by small doses of gamma-radiation]. / Funktsional'nye vzaimootnosheniia mezhdu degidrogenazami i transaminazami v razlichnykh otdelakh golovnogo mozga krys pri deistvii malykh doz gamma-izlucheniia.

Wistar rats were exposed to 10, 20 and 40 sGy of gamma-irradiation. Maximal activity of 2-oxoglutarate- and succinate dehydrogenases, as well as of aspartate-2-oxoglutarate and pyruvate-2-oxoglutarate in the brain tissue was measured within 30 days after the exposure. Dehydrogenase activity was measured in the brain cortex, limbic system and in the cerebellum; transaminase activity was determined in the brain cortex, diencephalic zone and in the hypophysis. It was found that small doses of irradiation resulted in an oscillating increase of dehydrogenase activity with a decrease of the amplitude by the 30th day of the experiment. As the dose of irradiation increases, the periods of normal activity change into phases of inhibition of dehydrogenase action, the period of oscillations diminishes. Transaminase activity, as a rule, changes in a phase in a reversible manner as compared with dehydrogenase activity. These observations are discussed from the point of view of structural relations between these two systems in the intramitochondrial supramolecular structures, the so-called metabolons.

[Functional status of perfused livers of irradiated rats]. / Funktsional'noe sostoianie perfuziruemoi pecheni obluchennykh krys.

Liver of X-ray irradiated rats /a dose of 18.06.10(-2) Ci per kg of body mass/, deprived of the body homeostatic influences, exhibited increased functional activity within the first day after irradiation: intensity of transamination was increased in mitochondria and supernatant as well as output of glucose and urea was elevated. Sensitivity to substrate stimulation of transamination and gluconeogenesis reactions was decreased in the liver within 3 days after irradiation.

[Effect of chemical modification and carboxylate anions on transamination of phenylalanine and alanine in the active center of chicken cytosol aspartate transaminase]. / Vliianie khimicheskoi modifikatsii i karboksilat-anionov na transaminirovanie fenilalanina i alanina v aktivnom tsentre tsitozol'noi aspartat-transaminazy kur.

Photooxidation of a histidine residue in aspartate transaminase leads to proportionate loss of the enzyme activity in reactions with L-aspartate and L-phenylalanine. Modification of two arginine residues by 1,2-cyclohexanedione strongly inhibits transamination of aspartate but, in contrast, slightly increases the rate of phenylalanine transamination. A stimulatory effect of a number of aromatic and aliphatic monocarboxylate anions on the rate of alanine transamination in the active site was observed. Indolylbutyrate was the most effective compound among those tested. Indolylbutyrate and indolylacetate act as competitive inhibitors in the case of transamination of phenylalanine or aspartate. The results were interpreted as indicating the presence in the active center of transaminase of a hydrophobic subsite participating in the binding of aromatic aminoacids.

[Effect of space flight and of the accompanying radiation on amino acid metabolism in the skeletal muscle of rats]. / Vliianie kosmicheskogo poleta i soputstvuiushchei radiatsii na aminokislotnyi obmen v skeletnoi myshtse u krys.

It was demonstrated that a combined effect of 20.5-day space flight and gamma-irradiation reduced the content of biologically important amino acids (methionine, phenylalanine, serine, aspartic and glutamic acids) and inhibited the activity of aspartate aminotransferase of sarcoplasmatic proteins in the quadriceps muscle of rats. Comparison of these data with the Cosmos-605 results and literature reports suggested that gamma-irradiation inhibited the synthetic processes in the skeletal muscle.

Rat brain metabolism enzyme activity variations following He-Ne laser irradiation.

In order to gain insight into the metabolic modifications induced in rat brain tissues by helium-neon (He-Ne) laser irradiation, in the research described here, we investigated the variations in the activity of the enzymes aspartate transferase (AST, EC 2.6.1.4), both cytosolic and mitochondrial, glutamate dehydrogenase (GIDH, EC 1.4.1.3), and total superoxide dismutase (SOD, EC 1.15.1.1), in the brain of rats treated with a very small dose (1.08 J) of He-Ne laser radiation. The rats were sacrificed 4 h after the treatment. The enzymes were evaluated spectrophotometrically in brain extracts of irradiated animals and also in untreated rats (controls) and rats that underwent simulated treatment (stressed). The data obtained from 5-10 animals assayed individually showed that, in the in toto brain tissues of the irradiated rats compared to the stressed rats, there was a marked increase of total SOD, together with an appreciable decrease of cytosolic AST, and insignificant variations in mitochondrial AST and GIDH. Stress alone caused a considerable decrease of total SOD and small but statistically significant increases of s-AST, m-AST, and GIDH.

Variation of transaminases and lactate dehydrogenase in irradiated Biomphalaria alexandrina snails.

Effect of ultraviolet and gamma radiations on the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LD) in Biomphalaria alexandrina snails, the specific intermediate host of schistosomiasis, was investigated. Changes in the electrophoretic pattern of LD in the species under study were also taken as a measured parameter and the effect of gamma-irradiation on the glutathione content in the haemolymph of the snails have been included.

Radiation-induced enzyme efflux from rat heart: sedentary animals.

Serum levels of lactate dehydrogenase, creatine kinase, and glutamate oxaloacetate transaminase show initial elevations within 12 hr of exposure to 2,000 rads of gamma-radiation to the thoracic region of rats. Significant decreases in heart muscle homogenate levels of these enzymes parallel initial elevations in the serum and may suggest that enhanced leakage of enzymes is a consequence of radiation injury to heart muscle. Insignificant alterations in mitochondrial glutamate oxaloacetate transaminase levels after exposure indicate that in vivo injury to the mitochondria from therapeutic levels of gamma-radiation is questionable. The results support the contention that ionizing radiation instigates alterations in the dynamic permeability of membranes, allowing leakage of biologically active material out of the injured cell.

[Modification with dyes of the effects of laser irradiation on various enzymes of glutamic acid metabolism]. / Modifikatsiia krasiteliami éffektov lazernogo vozdeistviia na nekotorye fermenty obmena glutaminovoi kisloty.

In the in vivo experiments it has been shown that a mixture of low-intensity helium-neon laser radiation and dyes modifies the effect of laser radiation on the activity of basic enzymes of glutamic acid metabolism.

[Aspartate aminotransferase and glutamate dehydrogenase activity in the rat brain during infrared laser exposure]. / Aktivnost' aspertataminotransferazy i glutamatdegidrogenazy v golovnom mozge krys pri infrakrasnom lazernom vozdeistvii.

In experiments in vivo it was shown that upon low-intensity infrared irradiation changes in the activity of main enzymes of glutamic acid metabolism are a function of time of exposure and flux density.

Prevention of biochemical changes in gamma-irradiated rats by some metal complexes.

The formation of superoxide partially accounts for the well-known oxygen enhancement of radiation-induced biochemical changes and cell damage. Radioprotective effects of copper (II), manganese (IV) or vanadium (IV) complexes, of superoxide dismutase-mimetic activity, on body weight, survival rate and some biochemical parameters in pre-treated irradiated, untreated irradiated and treated non-irradiated female albino rats have been studied 24 h after whole body gamma-irradiation at a dose level of 6 Gy. Survival time, body weight, red blood cell (RBC) and white blood cell (WBC) counts, hemoglobin (Hb) concentration, percentage of hematocrit (Hct%), reduced glutathione (GSH), serum total protein, albumin, globulin (G), blood urea, creatinine and cholesterol were estimated, as well as the activities of blood superoxide dismutase (SOD), glutamate-oxaloacetic (GOT) and glutamate-pyruvic (GPT) transaminases, and alkaline phosphatase were assessed. A significant decline was shown in body weight, survival rate, the mean values of RBC and WBC counts, Hb and Hct percentages, and GSH concentration, as well as blood SOD activity, in whole body gamma-irradiated rats compared with the control non-irradiated rat group. The mean activity values of alkaline phosphatase, GOT and GPT, as well as the average values of blood urea, creatinine, total cholesterol, total protein and globulin were significantly elevated, while the average values of albumin and the albumin/globulin ratio were decreased in gamma-irradiated rats compared with the corresponding values of the normal control rat group. Pretreatment of rats with either manganese or vanadium complexes resulted in a significant increase in survival rate and body weight over that of the non-treated irradiated rat group. Pretreatment of rats with copper (II), manganese (IV) or vanadium (IV) complexes caused a significant increase in RBC and WBC counts, Hb concentration, HCt (%), GSH content and SOD activity in blood when compared to the irradiated rat group without treatment. The administration of copper (II), manganese (IV) or vanadium (IV) complexes prior to irradiation exposure resulted in a significant decrease in GOT and GPT activities in addition to blood urea, creatinine, cholesterol, globulin and total protein contents, while each complex exhibited a significant increase in plasma alkaline phosphatase, albumin, and the albumin/globulin ratio compared to the untreated irradiated rat group. Administration of vanadium (IV), manganese (IV) or copper (II) complexes in non-irradiated rats caused a significant increase in SOD activity without changing other biochemical parameters compared with the corresponding values of the normal control rat group. We conclude that these metallo-elements, particularly manganese (IV) and vanadium (IV) complexes of 2-methylaminopyridine, have radiation protection and radiation recovery. Furthermore, these metal complexes offer a new approach to overcome the pathological effects of ionizing radiation and suggest their use as a physiological approach to preventing or perhaps predominantly facilitating recovery from radiation injury.