Comparison of the Effects of Intraperitoneal Injection with Carbon Tetrachloride on Acute Liver Toxicity in Male and Female Kunming Mice.

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.

Date fruits inhibit hepatocyte apoptosis and modulate the expression of hepatocyte growth factor, cytochrome P450 2E1 and heme oxygenase-1 in carbon tetrachloride-induced liver fibrosis.

CONTEXT: Date fruits have protective effects against liver fibrosis; however their anti-apoptotic effects have not been investigated. OBJECTIVE: To investigate the modulating effects of date fruits on pro- and anti-apoptotic markers, cytochrome P450 2E1 (CYP2E1) and hepatocyte growth factor (HGF) in liver fibrosis. MATERIALS AND METHODS: Liver fibrosis was induced by injection of carbon tetrachloride (CCl4) for eight weeks. Date flesh extract (DFE) and pits extract (DPE) were taken daily concomitant with CCl4. Hepatocyte apoptosis was determined by measuring the expression of Fas, caspase-3, Bax, Bcl2 and hemeoxygenase-1 (HO-1). Hepatic levels of HGF and CYP2E1 were determined. RESULTS: Treatment with DFE and DPE significantly attenuated the elevated levels of Fas, caspase 3, Bax and CYP2E1 induced by CCl4. In addition, they alleviated the reduction in Bcl2, HGF and HO-1, the cytoprotective and anti-apoptotic factors in liver. Conclusions DFE and DPE treatment can ameliorate liver fibrosis by inhibiting hepatocyte apoptosis.

IN VITRO AND IN VIVO EVALUATION OF ANTIMICROBIAL AND ANTIOXIDANT POTENTIAL OF STEVIA EXTRACT.

BACKGROUND: The current trend globally is the utilization of natural products as therapeutic agents given its minimum side effects. The leaves of Stevia contain several active ingredient compounds such as rebaudioside. Stevia extract have been used for many purposes. Active oxygen radicals can induce base modifications, DNA breakage, and intracellular protein crosslink's. This study was done to evaluate the potential of stevia extract as antibacterial and antioxidants actions. MATERIALS AND METHODS: Antibacterial activity of different extracts of stevia was tested in vitro against different species of bacteria and hepato-protective efficacy was testes in rats injected with CCl4 as hepatotoxic. RESULTS: Acetone extract exhibited antibacterial activity against selected five bacteria species. The acetone extract suppressed the elevation of serum ALT (p <0.05) and AST (p <0.001) activities induced by CCl4. Animals given stevia extract showed prevention against deleterious effects of CCl4 by lowering lipid peroxidation and enhancement of antioxidant activities as SOD and CAT. The protection trial is better than treatment trial. Total phenolic content of aqueous and acetone extracts were found 30 mg and 85 mg gallic /gm extract respectively. While the total flavonoids were 40 mg and 80 mg quercetin/g respectively. The GC-MS analysis showed that monoterpene and indole are the main components. Aqueous extract don't show any antibacterial activity against the tested strains. The antioxidant properties were attributable to its phenolic content to scavenge free radicals. CONCLUSION: Acetone extract possess a potent antimicrobial and activity against deleterious effect of CCl4-caused liver damage.

[Correction of the lipid composition of the liver plasma membranes during heliotrine intoxication]. / Korrektsiia lipidnogo sostava plazmaticheskikh membran pecheni pri geliotrinovoi intoksikatsii.

Antioxidant properties of yantocine, a preparation derived from Alhagi pseudalhagi Desy, were studied on a model of acute toxic hepatitis induced in random bred young male albino rats (90-100 g). Two experimental models were used: acute geliotrine hepatitis and acute CCl4 hepatitis. Yantocine was added to preparations of damaged plasma membranes (PM) in ascending doses. The results indicate that the level of malonic dialdehyde in the rat liver PM depended on the drug dose in both models of hepatitis. Linear dependence was observed for doses of 1.0-5.0 gamma. The capacity of yantocine to decrease the production of lipid peroxided was confirmed in vivo. After 3-day treatment with yantocine the level of lipid peroxides decreased by 15 and 12%, respectively, while the content of total phospholipids increased negligibly.

[The pathogenesis, clinical picture and treatment of poisonings by organic solvents, derivatives of chlorinated hydrocarbons (trichloroethylene, carbon tetrachloride)]. / Patogenez, klinika i lechenie otravlenii nekotorymi organicheskimi rastvoriteliami, proizvodnymi khlorirovannykh uglevodorov (trikhlorétilen, chetyrekhkhloristyi uglerod).

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.

Fatal accidental ingestion of carbon tetrachloride: a postmortem distribution study.

This paper reports a fatality involving a 75-year-old white male, who ingested an unknown quantity of carbon tetrachloride (CCl4)--a toxic agent able to induce central nervous system depression and severe renal and hepatic damage--and who died after two days of intensive care. The analytical assessment of CCl4 concentration was performed on several biological fluids and tissues employing gas chromatography-flame ionization detection (GC-FID) head space method. Both urine (328.5 mg/L) and bile (169.8 mg/L) had high concentrations of CCl4, proving that the chemical undergoes extensive urinary and biliary excretion. In accordance with the high clearance power of lungs, systemic venous blood, (143.4 mg/L) had a concentration of CCl4 almost two and half times greater than in arterial blood (57.5 mg/L), representing the best specimen to correlate CCl4 blood concentration with the deep of narcosis. Vitreous humor, (170.5 mg/L) concentration of CCl4 proves the capability of the chemical to enter eyes and its relatively slow release into the systemic blood. Pancreas (657.9 mg/kg), brain (243 mg/kg) and testis (237.3 mg/kg) have great affinity for CCl4. The concentrations of the chemical in brain are cortex: 243.2 mg/kg, basal ganglia: 216.1 mg/kg, medulla oblongata: 243.3 mg/kg and cerebellum: 175.3 mg/kg. As the depth of narcosis is correlated with CCl4 concentration, brain represents the most suitable tissue for toxicologic analysis. Lower concentrations of the chemical are found in lungs (127.3 mg/kg), kidneys (150.5 mg/kg), muscle (71.1 mg/kg), myocardium (78.5 mg/kg) and spleen (68.3 mg/kg). Liver (58.6 mg/Kg), a frequently analyzed tissue in forensic toxicology, shows the lowest concentration.

Pyrazole treatment of rats potentiates CCL4-but not CHCL3-hepatotoxicity.

Rats were treated with pyrazole to increase the liver content of the "alcohol-inducible" form of cytochrome P-450. This treatment increased the sensitivity of these animals to CCl4-hepatotoxicity assessed by increases in SGPT and SGOT levels and decreases in microsomal cytochrome P-450 and aniline p-hydroxylase activity. However, the hepatotoxicity of CHCl3 was not increased by pyrazole-treatment. These data are consistent with the hypothesis that the "alcohol-inducible" form of cytochrome P-450 is capable of CCl4- but not CHCl3-activation.

Respiratory exposure of grain inspection workers to carbon tetrachloride fumigant.

Carbon tetrachloride (often mixed with carbon disulfide or ethylene dichloride) is a common constituent of liquid grain fumigants. Applied as liquids, these mixtures volatilize and achieve vapor concentrations sufficient to control insect infestations in stored grains. Absorbed grain desorbs fumigant components after the fumigation period, and it then becomes a source of exposure to workers who handle fumigated grain. Carbon tetrachloride meets the EPA's risk criteria for hepatotoxicity, nephrotoxicity and oncogenicity, and it has been under regulatory review since 15 October 1980. Present OSHA standards for CCl4 are a time-weighted average (TWA) of 10 ppm and an acceptable ceiling of 25 ppm. ACGIH and NIOSH have recommended lowering the OSHA standard. The point at which peak exposure occurs during the grain inspection process has been identified as the off odor test in which the inspector smells the grain sample for rancidity, sourness, etc. Ambient concentrations of CCl4 in 7750 grain samples submitted for inspection were determined by colorimetric tube, and these concentrations were an estimate of peak grain inspector exposure to CCl4. The average ambient concentration of CCl4 per grain sample was 1.69 ppm +/- 8.35. Approximately 380 TWA CCl4 exposures for grain inspection workers were determined by using passive dosimeters. All TWA exposures were less than 2 ppm. Variables are examined, such as location of work, grain type, time of year and grain transportation vehicle--all of which are known to the sampler or inspector before performing their job functions and which affect potential exposure.

Outbreak of carbon tetrachloride poisoning in a color printing factory related to the use of isopropyl alcohol and an air conditioning system in Taiwan.

Three workers from a color printing factory were admitted to community hospitals in 1985 with manifestations of acute hepatitis. One of the three had superimposed acute renal failure and pulmonary edema. An investigation was subsequently conducted at the plant to determine the etiology of the outbreak and the prevalence of liver disease among the remaining workers. Comprehensive medical evaluations were conducted, which included physical examinations, liver function tests, and serological screening for hepatitis. Seventeen of 25 workers from the plant had abnormal liver function tests 10 days after the outbreak, and a significant association was found between the presence of abnormal liver function tests and a history of recently having worked inside any of three rooms in which an interconnecting air conditioning system had been installed to cool the printing machines. After further investigation, it was determined that the incident occurred following inadvertent use of carbon tetrachloride to clean a pump in the printing machine. A simulation of the pump cleaning operation revealed ambient air levels of carbon tetrachloride of 300-500 ppm. Ultimately, it was concluded that the outbreak was in all likelihood due to the combined use of carbon tetrachloride and isopropyl alcohol in the cleaning operation. This outbreak underscores the importance of adopting appropriate industrial hygiene measures in a rapidly industrializing nation such as Taiwan.

Carbon tetrachloride toxicity as a model for studying free-radical mediated liver injury.

A single dose of CCl4 when administered to a rat produces centrilobular necrosis and fatty degeneration of the liver. These hepatotoxic effects of CCl4 are dependent upon its metabolic activation in the liver endoplasmic reticulum to reactive intermediates, including the trichloromethyl free radical. Positive identification of the formation of this free radical in vivo, in isolated liver cells and in microsomal suspensions in vitro has been achieved by e.s.r. spin-trapping techniques. The trichloromethyl radical has been found to be relatively unreactive in comparison with the secondarily derived peroxy radical CCl3O2., although each free radical species contributes significantly to the biological disturbances that occur. Major early perturbations produced to liver endoplasmic reticulum by exposure in vivo or in vitro to CCl4 include covalent binding and lipid peroxidation; studies of these processes occurring during CCl4 intoxication have uncovered a number of concepts of general relevance to free-radical mediated tissue injury. Lipid peroxidation produces a variety of substances that have high biological activities, including effects on cell division; many liver tumours have a much reduced rate of lipid peroxidation compared with normal liver. A discussion of this rather general feature of liver tumours is given in relation to the liver cell division that follows partial hepatectomy.

Target organ toxicology of halocarbons commonly found contaminating drinking water.

Some of the most frequent drinking water contaminants are organic halocarbons. This paper will initially summarize the target organ effects of three halocarbons: 1,2-dichloroethane, tetrachloroethylene, and trichloroethylene. Following the brief summaries, a more detailed description of the oral hepatoxicity of carbon tetrachloride is presented. Data are provided that indicate that the hepatotoxicity of carbon tetrachloride is enhanced when administered by corn oil gavage when compared to aqueous suspension gavage.

[A case of carbon tetrachloride poisoning]. / Un cas d'intoxication aiguë par la tétrachlorure de carbone.

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.

Studies on the mechanism of enhancement of carbon tetrachloride hepatotoxicity by Triton WR 1339.

Pretreatment of rats with Triton WR 1339 significantly enhanced the intensity of CC14-induced liver necrosis. Previous workers suggested that this effect might be due to enhancement by Triton WR 1339 of cellular degradative processes. This pretreatment, however, also enhanced the intensity of covalent binding of [14C]CC14 metabolites to microsomal protein at 3 or 6 h, but not 1 h after its administration. This effect is not due to changes of microsomal P-450 content or increased activity of mixed-function oxygenase-metabolizing drugs like pentobarbital. Pretreatment with Triton WR 1339 also partially increased CC14-induced peroxidation of microsomal lipids at 1, 3 or 6 h after administration of the hepatotoxin. Liver concentrations of CC14 in Triton WR 1339-treated rats were significantly higher at 3 or 6 h but not at 1, 10 or 24 after its i.p. administration. Triton WR 1339 treatment decreased the body temperature of the rats and further intensified the decrease produced by CC14. Results suggest that, in addition to possible effects of Triton WR 1339 administration on liver-cell degradative processes, there are other actions of this detergent on CC14 activation and lipid peroxidation which might play a role in the heightened response of the liver of CC14-induced injury.

[Effect of Kupffer cell blockade on the development of acute toxic hepatitis]. / Vliianie blokady kletok Kupfera na razvitie ostrogo toksicheskogo gepatita.

The blockade of Kupffer cells was induced in Wistar rats by intravenous injection of colloid iron, brand P-100 phi, in a 5% starch followed after two hours by subcutaneous administration of 0.2 ml of 40% CCl per 100 g body weight. During the blockade of course of CCl4-induced acute hepatitis was significantly modified that was shown by the tendency to scattering of hepatocyte injury and by delayed liver tissue recovery.