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BACKGROUND Acute chemical liver injury needs to be further explored. The present study aimed to compare the effects of intraperitoneal injection with carbon tetrachloride on acute liver toxicity after 24 h in male and female Kunming mice. MATERIAL AND METHODS In this study, female and male mice were simultaneously divided into 3 different groups. Each group was treated differently, and after 24 h, blood samples were collected to check for changes in the activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), which were used to assess liver toxicity. Liver samples were used for hematoxylin-eosin staining, and periodic acid Schiff reagent staining was performed to detect the pathological changes of each group. The expression level of biomarker molecules in liver cells was also systematically analyzed. RESULTS Our results showed that, compared with male mice, female mice showed more serious damage: reduced glycogen and higher degree of necrosis, and the levels of heatshock protein 27 (HSP27), heat-shock protein 70 (HSP70), proliferating cell nuclear antigen (PCNA) and B cell lymphoma/lewkmia-2 (Bcl-2) were significantly lower than in the male group (P<0.05 or P<0.01), while the results of Bcl-2-associated X protein (Bax), cysteinyl aspartate specific proteinase 3 (Caspase3), and cytochrome P450 2E1 (CYP2E1) were the opposite (P<0.05 or P<0.01). CONCLUSIONS The findings from this study showed that, compared with male mice, at 24 h after CCl₄ toxicity, female mice showed more severe changes of hepatocyte necrosis and PAS-positivity, with significantly reduced expression of HSP27, HSP70, PCNA, and Bcl-2, and significantly increased expression of Bax, caspase-3, and CYP2E1.

We have previously reported that radon inhalation activates anti-oxidative functions and inhibits carbon tetrachloride (CCl(4))-induced hepatopathy. It has also been reported that antioxidant vitamins can inhibit CCl(4)-induced hepatopathy. In the current study, we examined the comparative efficacy of treatment with radon, ascorbic acid and α-tocopherol on CCl(4)-induced hepatopathy. Mice were subjected to intraperitoneal injection of CCl(4) after inhaling approximately 1000 or 2000 Bq/m(3) radon for 24 h, or immediately after intraperitoneal injection of ascorbic acid (100, 300, or 500 mg/kg bodyweight) or α-tocopherol (100, 300, or 500 mg/kg bodyweight). We estimated the inhibitory effects on CCl(4)-induced hepatopathy based on hepatic function-associated parameters, oxidative damage-associated parameters and histological changes. The results revealed that the therapeutic effects of radon inhalation were almost equivalent to treatment with ascorbic acid at a dose of 500 mg/kg or α-tocopherol at a dose of 300 mg/kg. The activities of superoxide dismutase, catalase, and glutathione peroxidase in the liver were significantly higher in mice exposed to radon than in mice treated with CCl(4) alone. These findings suggest that radon inhalation has an anti-oxidative effect against CCl(4)-induced hepatopathy similar to the anti-oxidative effects of ascorbic acid or α-tocopherol due to the induction of anti-oxidative functions.

The anti-oxidant activities of fucosterol isolated from the marine algae Pelvetia siliquosa were investigated. Fucosterol exhibited a significant decrease in serum transaminase activities elevated by hepatic damage induced by CCl4-intoxication in rats. Fucosterol inhibited the sGOT and sGPT activities by 25.57 and 63.16%, respectively. Fucosterol showed the increase in the anti-oxidant enzymes such as hepatic cytosolic superoxide dismutase (SOD), catalase and glutathione peroxidase (GSH-px) activities by 33.89, 21.56 and 39.24%, respectively, in CCl4-intoxicated rats. These results suggest that fucosterol possess not only the anti-oxidant, but also the hepatoprotective activities in rats.

Poisoning resulting from exposure to a wide variety of industrial chemicals is not a common occurrence in horses, but it does happen on occasion. A wide range of toxicosis can occur from a wide range of industrial pollutants, such as dioxin, carbon tetrachloride, and tetrachloroethylene, to heavy metals, such as cadmium and zinc. The equine practitioner must consider industrial chemical toxicosis in differential diagnoses and work with a reputable veterinary diagnostic laboratory to confirm or rule out industrial chemical poisoning.

Clinical studies and experiments on laboratory animals covered mechanism of trichloroethylene toxicity. The chemical and its metabolites cause nonspecific toxic effects in membranes and therefore induce energy metabolism disorder that is proved to be a trigger of pathologic process in the intoxication. Experimental studies failed to disclose and explain mechanism of compromised calcium metabolism and its role in cardiac manifestations seen in trichloroethylene poisoning.

Cases of severe acute carbon tetrachloride poisoning are sporadically described in Spain. We report the cases of three patients that inhaled toxic vapour of carbon tetrachloride that they used as a solvent during their working activity. They developed hepatic disfunction and one of them acute renal failure. The interval between the labour exposure and the medical care was higher than 24 hours. All the patients received N-acetylcysteine treatment (300 mg/kg) and oxygen. The patient ith renal failure recurred hemodialysis. The basic aspects of diagnosis and treatment are commented.

Following single administration of carbon tetrachloride (p.o., 200 microliters/200 g) to female rats, activities of transaminases AST and ALT were determined from 1 hr to 7 days after the intoxication. At the same time intervals, aminopyrine breath test (ABT) was applied. The results indicate that marked decrease of ABT was observed within the first 3 hrs of exposition and lasted 24 hrs. On the other hand, statistically significant elevation of plasma enzymes was demonstrated from the 3rd hr of administration and lasted also 24 hrs. The results indicate that ABT reacts more rapidly to carbon tetrachloride administration than the changes of plasma transaminase.

CCl4 and related compounds, such as halothane, are metabolized by the liver to form free radical intermediates, which are thought to be implicated in the hepatotoxic response. Two to three hours following CCl4 exposure (i.p.) there is a localized edematous region surrounding the portal vein which is observable by proton MRI in vivo. Enhancement of the CCl4-induced edematous region was possible using Gd-DTPA, a paramagnetic contrast agent. However, with the use of a nitroxide contrast agent (3-PCA) there was no enhancement, but rather a significant diminution of the CCl4-induced edematous response. These results suggest that the nitroxide contrast agents, which are themselves free radicals, act as free radical scavengers and therefore reduce the formation of the CCl4-induced hepatic 'damage' observed in proton MR images.

Industrial carbon tetrachloride is used in the synthesis of chlorofluorocarbons and chlorinated solvents. Although both production and use of carbon tetrachloride are declining, industrial and hazardous waste sites remain as sources of exposure. Workers using carbon tetrachloride or products that contain it are at highest risk of exposure. Diabetics and persons who drink alcohol may have an increased risk of adverse effects following exposure to carbon tetrachloride. Acute exposure may result in rapid central nervous system depression. Symptoms of hepatic and renal toxicity may arise one to four days later. Carbon tetrachloride is considered a possible carcinogenic agent. Administration of N-acetylcysteine may reduce complications of severe carbon tetrachloride exposure. Removal of the source of exposure and avoidance of other hepatotoxicants is the only treatment for chronic carbon tetrachloride toxicity.

In vivo 1H and 23Na magnetic resonance imaging (MRI) and 31P magnetic resonance spectroscopy (MRS) techniques were used to study CCl4-induced acute hepatotoxicity in rats in situ. One or two hours following exposure to CCl4, a localized edematous region was detected in the liver by 1H MRI. The CCl4-induced edema was localized in a region surrounding the hepatic portal vein. With the use of a 23Na/1H double frequency tuned bird-cage imaging coil an increase in Na+ ion flux was also observed in the same region as the edematous region detected by 1H-MRI. Pretreatment with alpha-phenyl-tert-butyl nitrone (PBN), a free radical spin trap, 30 min prior to CCl4 exposure, was found to reduce the CCl4-induced edematous response in the liver observed in either 1H or 23Na-NMR images. Inhibition of the CCl4-induced edematous response in rat liver by PBN demonstrates that free radical intermediates, arising from the metabolism of CCl4, are possibly the key causal agents in the initiation of the edematous response. In addition, with the use of a 31P/1H double frequency tuned bird-cage imaging/spectroscopy coil, localized 31P spectra (ISIS) were obtained from the regions of CCl4-induced "tissue damage" observed in the 1H-MRI images. The most notable changes observed from the 31P spectra were an increase in inorganic phosphate (Pi) and a decrease in hepatocytosolic pH in the CCl4-treated rat livers in comparison to saline-treated control livers.

Magnetic resonance imaging (MRI) and spectroscopy (MRS) were used to follow the time course of ethanol-induced fatty liver in a group of 10 rats fed a diet containing 12% alcohol (ethanol) over a 5-week period. The MR data consisted of T1-weighted images, in vivo 1H spectra, and in vivo T1 relaxation measurements. Changes in short TR images as a result of fatty accumulation were noted only as a slight increase in liver intensity relative to surrounding muscle. A poorly correlated (r = 0.54) increase in water T1 with time was observed. No statistically significant changes in lipid T1 were found. MRS derived lipid content was compared with biochemically derived total lipids and histology. MRS determined liver lipids were found to increase linearly with time (r = 0.91). Biochemically derived lipid content also increased with prolonged exposure to ethanol (r = 0.96). The averages of MRS derived lipid content agreed well with the average changes in biochemically determined total lipid concentration. Histologic examination revealed slight to moderate changes in fatty accumulation with significant variation in the group at the end of the study. On an individual basis the MRS and histologic evaluation were highly correlated (r = 0.94).

Magnetic resonance imaging techniques were used to investigate the response of the liver of the rat in situ to a toxicological challenge by carbon tetrachloride. Proton images were taken as transverse slices through the rat before and after intraperitoneal administration of the hepatotoxin. Two to three hours after carbon tetrachloride was given, a region of high proton signal intensity was observed where the portal vein enters the liver. Sodium-23 images were also taken, and a region of high sodium intensity was observed in the same location within the liver as the increased proton intensity. The results suggest that acute administration of carbon tetrachloride induces localized liver damage in the region where the hepatotoxin first enters the liver. This liver damage is manifest as edema with a buildup of sodium ion and water, which can be readily detected by sodium-23 and proton NMR imaging techniques, respectively.

Dynamics of distribution and excretion with urine of 125I-p-iodophenamine were studied impairment of rat liver tissue microsomal oxidation by means of CC14 treatment. This poison inhibited distinctly metabolism and excretion of the labelled compound in rats but not in rabbits, which was due to difference in the mechanisms of the compound biotransformation. The requirements for compounds suitable for studies of microsomal oxidation by means of excretory test were not met by 125I-p-iodophenamine.

The enzymic tests and radionuclide hepatography were used to study and compare liver function after rabbits were exposed to tetrachloromethane poisoning. The activity of serum enzymes of cholinesterase, alkaline phosphatase, aldolase and leucine aminopeptidase was determined. Hepatography was made with the use of 198Au-colloid with an activity 0.74 MBC. The enzymic tests were demonstrated to be more sensitive than radionuclide hepatography in detecting the earliest parenchymatous lesions in the liver. The data obtained correlate with the data of the pathohistological examinations, which demonstrated the presence of marked vacuole parenchymatous fatty dystrophy. The authors recommend that the enzymic tests should be used for detecting early hepatic lesions induced by tetrachloromethane.

Peptidase-free L-amino-acid oxidase was purified from venom of Agkistrodon caliginosus and was used for the determination of serum peptidase (EC 3.4.1.-) activity with L-Leu-L-Leu as substrate. The peptidase activity in human serum rose remarkably in liver diseases, and had a significant correlation with serum transaminase activity. The peptidase activity in serum of rats treated with CCl4 was higher than that of normal rats. After Cellogel electrophoresis the zymogram of peptidase from human liver using di- or tripeptide as substrate appeared with three active bands; however, peptidase in serum of a patient with acute hepatitis showed only one active band.

An experimental model for monitoring rat liver function during protracted exposure to hepatotoxic agents is proposed. Owing to their invasiveness, the models usually employed are appropriate for studying the mechanism of action of toxic substances, but do not allow the liver situation to be followed over the course of time. The need to sacrifice animals to determine liver triglycerides-one of the key parameters in the progress of toxic damage- reduces the possibility of following such progress in the same animals. This study describes the testing of a model for monitoring three basic parameters of liver injury: cytolysis, steatosis and metabolic deficiency of the liver. CCl4 has been chosen as model-hepatotoxin. Steatosis is determined by evaluating the triglyceride content of small specimens of liver, obtained through open-field biopsies, which appear to be representative of the whole liver. Fatty liver is paralleled by the block in Triton-induced hypertriglyceridaemia. Determination of serum triglycerides derives from a very poorly invasive technique which can be repeated several times. The combination of these tests with the assessment of both the cytolysis (ALT and SDH release into the circulation) and the impairment of the efficiency of liver microsomal enzymes (TMO clearance), seems to offer a reliable experimental procedure in predicting the hepatotoxic effect of xenobiotics.

Cytochemical methods were used to explore the changes in the activity of redox (succinate dehydrogenase, mitochondrial alpha-glycerophosphate dehydrogenase) and hydrolytic (acid, alkaline phosphatase, myeloperoxidase) enzymes of peripheral blood leukocytes of random-bred albino rats during simulation of toxic hepato-, nephropathy and hemic hypoxia of different gravity. The studies of the changes of leukocyte distribution according to the activity of the above enzymes were demonstrated to be informative for the diagnosis of prepathological conditions. The possibility was also shown of differentiating the gravity of the pathological conditions with the aid of an analysis of the enzymes under study by the method of linear discriminant functions.

Carbon tetrachloride is a toxic solvent easily obtained in our country. 3 cases of poisoning by accidental inhalation at place of work. The main clinical manifestations were acute renal failure and toxic hepatopathy. All patients, had a good evolution with dialysis therapy after a few weeks. We comment on some possible additional therapies to be used in treating patients with severe poisoning due to carbon tetrachloride.

Studied was the dynamics of the changes taking place in the activity of a number of enzymes in the blood plasma (glutamate oxalacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), lactate dehydrogenase (LDH), alkaline phosphatase (AP), aldolase (ALD), creatine phosphokinase (CPK), guanase, and cholinesterase (CE). The calculation of the correlation coefficients and the regression lines revealed that GOT, GPT, LDH, ALD, and guanase raised their activity following treatment of the test animals up to a higher extent and at a higher rate. Lower rate changes were those in the activity of AP, leucinaminopeptidase, and CE. No changes whatever were found in the activity of CPK. On the basis of these results the diagnostic value is determined of both the individual enzymes and the enzyme constellation as a whole.

The authors present a case of severe poisoning as a result of ingestion of a considerable amount of Carbon Tetrachloride, where toxic hepatitis and hepato-nephritis, neurological occurrences and sexual disturbances appeared. There was a considerable decline of the libido, complete impotence during several months. The accident occurred owing the ignorance of the instructions, unlabelled toxic material as such and not keeping it in a safe place. The Hamsin - a hot and dry wind - played an important part in the quick and severe appearance of the poisoning. The sexual disturbances which did not exist before the poisoning, appeared immediately after the intoxication. They were apparently connected with the injury of the liver cells; they are similar to those induced under the influence of other toxic materials. The general condition, including the sexual disturbances improved, and patient returned to his normal working condition after a period of nine months.

The development of sensitive and specific radioimmunoassay for ligandin, a protein present in abundance in the hepatic cytoplasm, has permitted measurement of ligandin in rat plasma. Plasma ligandin levels were estimated in normal, carbon tetrachloride (CCl4)-treated, and bile duct-ligated rats, with parallel estimation of serum glutamic oxaloacetic transaminase (SGOT). Plasma ligandin levels rose at a greater rate and to higher levels than did SGOT in CCl4-treated rats and showed a more linear increment to increasing doses of CCl4. A marked depletion of hepatic, but not renal ligandin, was associated with CCl4 poisoning. Twelve hours after acute bile duct ligation, both plasma ligandin and SGOT were moderately elevated, plasma ligandin returning to normal by 24 hr, at which time SGOT was still raised. The findings of this study indicate that plasma ligandin is a sensitive index of experimental hepatocellular necrosis.

Acute carbon tetrachloride poisoning in 19 patients was confirmed by means of laboratory analysis of blood specimens. The whole-blood carbon tetrachloride concentrations ranged from 0.1-31.5 mg/l. Vomiting (11 patients), abdominal pain (5), diarrhoea (4), and coma/drowsiness (6) were the commonest symptoms and signs. Out of 13 patients treated with intravenous acetylcysteine 7 showed mild hepatic damage, 1 had moderate hepatic damage, and 1 with a history of alcoholism sustained massive hepatorenal damage and needed haemodialysis. Of the 6 patients (1 lost to follow-up) who were not given acetylcysteine 3 had hepatorenal failure and needed dialysis, and 1 died. The possibility of carbon tetrachloride poisoning after ingestion of, or exposure to, chlorinated hydrocarbons and in patients presenting with hepatic or renal impairment without obvious cause should not be ignored. Prompt treatment with acetylcysteine may minimise subsequent hepatorenal damage.

Changes in serum enzyme levels, liver histology and liver function tests have been correlated to determine the usefulness of these tests in assessing liver status. The effects of carbon tetrachloride administration on these parameters has been determined in a group of 20 sheep. Normal levels, elevated levels after injury and the effect of elapsed time after injury are reported for serum glutamic dehydrogenase, sorbitol dehydrogenase, glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, lactate dehydrogenase, fructose-1-phosphate adlolase, alkaline phosphatase, cholesterol and proteins. Variation in the time of elevation of enzyme activities may be useful in determining the elapsed time between acute injury and serum sampling. In comparison to sheep fed an adequate diet, a diet with a restricted protein intake was associated with increased severity of histological lesions and decreased liver function.

Six calves were used to formulate a model of liver injury, following up the activity of the serum enzymes LAP, ALD, AP, GPT, GOT, OKT, and guanase. Studied were also the contents of blood sugar, calcium, phosphorus as well as some indices of the lipid metabolism. It was found that even with the least severe injuries of the liver there was a considerable rise of the OKT, guanase, GOT, GPT, and LAP activity. It is believed that the enzyme changes alone could serve as a specific index to detect the earliest injury of the liver.

Studied was the effect of CCI4 intoxication of guinea pigs on the dynamics of changes taking place in the level of the total lipids and the esterificated and unesterificated fatty acids. It was found that following treatment with CCI4 the amount of the total lipids in the blood rose by the eighth hour and reached its peak value at the 24th hour. The unesterificated fatty acids rose considerably, while the esterificated ones showed but a slight rise. It is concluded on the basis of correlation coefficients that the changes in the level of the unesterificated fatty acids have the highest diagnostic value in the tetrachlormethane intoxication of the liver.

Case histories of twelve patients treated for carbon tetrachloride poisoning at the Toxicological Clinic, Institute of Internal Medicine, Medical Academy of Cracow, during 1971-1975, ware analysed retrospectively. All patients were found to have developed some liver damage, two of them exhibiting acute renal failure, another two--impaired central nervous system. Nine of the patients developed changes indicative of adverse effects of carbon tetrachloride upon the cardiac muscle.

In experimental bile obstruction in dogs, the most sensitive change in blood plasma composition is the increase in alkaline phosphatase activity which occurs after eight hours. Maximum alkaline phosphatase activities (approximately 100 times normal values) occur between the fifth and the 14th day. The increase in activity is accompanied by smaller increases in gamma-glutamyl transferase activity, and total bilirubin concentration also increases to a smaller extent and less regularly. Cholestasis also induces an intense cytolysis which is demonstrated mainly by increases in glutamate dehydrogenase and alanine amino transferase activities which are more intense and lasting than those induced by 0.5 ml/kg carbon tetrachloride.

The authors investigate 20 cases of acute carbon tetrachloride (CCl4) poisoning representing 50% of all acute poisonings with organo-chlorate solvents admitted during a 5-year interval to Galaţi District Hospital. All our CCl4 acute poisoning cases were accidental, mild and moderate in form, and prevailed in man (80%). Depending on the ingested (more seldom) or inhaled amounts, CCl4 induces neurological and or digestive disturbances, parenchymatous involvements, prevalently hepatic (misdiagnosis of acute viral hepatitis and leptospirosis) or mixed, hepatorenal. Characteristic to the mixed form is the staged evolution of the clinico-biological manifestations, acute toxic hepatitis in the first week and acute toxic tubulo-interstitial nephropathy in the second one, both requiring proper management. Five selected cases are presented.