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.

Comparative study on the inhibitory effects of antioxidant vitamins and radon on carbon tetrachloride-induced hepatopathy.

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.

Anti-oxidant activities of fucosterol from the marine algae Pelvetia siliquosa.

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.

Industrial chemicals and the horse.

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.

[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.

[Carbon tetrachloride poisoning]. / Intoxicación por tetracloruro de carbono.

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.

Use of nitroxides as MRI contrast agents to study in vivo carbon tetrachloride induced hepatotoxicity in rats.

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.

Validity of two different methods to detect liver injury.

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.

Carbon tetrachloride toxicity. Agency for Toxic Substances and Disease Registry.

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.

Use of 1H/23Na and 1H/31P double frequency tuned birdcage coils to study in vivo carbon tetrachloride-induced hepatotoxicity in rats.

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.

In vivo NMR, biochemical, and histologic evaluation of alcohol-induced fatty liver in rat and a comparison with CCl4 hepatotoxicity.

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).

Sodium-23 and proton nuclear magnetic resonance imaging studies of carbon tetrachloride-induced liver damage in the rat.

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.

[Carbon tetrachloride poisoning: a report of 3 cases]. / Intoxicación por tetracloruro de carbono: presentación de tres casos.

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.