Carbon tetrachloride, damage

The effects of chromium(III) chloride and sodium chromate(VI) on the hepatotoxicity of carbon tetrachloride exposure to mouse hepatocytes were examined by Tezuka et al. (1995). Primary cultures of mouse hepatocytes were pretreated with 10 or 100 pM chromium for 24 hours followed by exposure to 1-5 mM carbon tetrachloride for up to 1 hour. Chromium(VI) pretreatment significantly reduced the cell toxicity as well as lipid peroxidation caused by carbon tetrachloride. Chromium(III) pretreatment did not have any effect on cell toxicity. About 50% of chromium(VI) was taken up and reduced in the cells by 90% to chromium(III) within 10 minutes. The initial uptake rate of chromium(HI) into cells was greater than 500-fold less than chromium(VI), and only about 5% was absorbed. The protection against carbon tetrachloride damage by chromium(VI) was attributed to its rapid uptake and conversion to chromium(III), and it was determined that chromium(III) acts as a radical scavenger for the free radicals generated by carbon tetrachloride within the cell. Furthermore, chromium(VI) pretreatment reduced the activity of NADPH cytochrome c reductase which metabolizes carbon tetrachloride to reactive species. 

Acute Liver Damage Several compounds (e.g., dimethyl iiitrosoamine, carbon tetrachloride, and thioacetamide) cause necrosis of hepatocytes by inhibiting pro tein syndiesis at the translational level, i.e., by inhibiting the addition of new amino adds into the protein chain being sjTithetized. This is not, however, the only mechanism. Ethioiiine is a compound which inhibits protein synthesis bur doe not induce... 

A number of early in vitro studies demonstrated a considerable role of free radicals in liver injury (see, for example, Proceedings of International Meeting on Free Radicals in Liver Injury [341]). Later on, it was shown that chronic inflammation in the liver-induced oxidative DNA damage stimulated chronic active hepatitis and increased the risk of hepatocarcinogenesis [342,343]. Farinati et al. [344] showed that 8-OHdG content increased in circulating leukocytes of patients with chronic hepatitis C virus (HCV) infection. DNA oxidative damage is supposedly an early event of HCV-related hepatitis. The formation of isoprostanes in the liver of carbon tetrachloride-treated rats can be suppressed by the administration of vitamin E [345],... 

Its effects on the body are widespread. Inhalation of the vapor is the most common mode of entry, and when the chemical is inhaled in sufficient concentration, it has an immediate effect on the brain (hence the high that Harry was partial to) and ultimately, over longer periods, it causes damage to the liver and kidneys. Now it so happened, that although Harry had been working for five years with concentrations of carbon tetrachloride above the recommended limit, any obvious damage to his brain, liver, and kidneys at that time was no more than he would have derived from knocking back a six pack of beer several times a week. So what was the trouble ... 

Toxicology. Carbon tetrachloride causes central nervous system depression and severe damage to the liver and kidneys it is carcinogenic in experimental animals and has been classified as a potential human carcinogen. 

A number of substances including ethanol, isopropyl alcohol, polybrominated biphenyls, phenobarbital, and benzo( )pyrene have been shown to synergistically affect carbon tetrachloride toxicity." Alcohol has been a concomitant factor in many of the human cases of poisoning, especially in cases in which severe liver and kidney damage have occurred. Some substances such as chlordecone greatly potentiate the toxicity of carbon tetrachloride at... 

The mechanism of carbon tetrachloride hepatotoxicity generally is viewed as an example of lethal cleavage, where the CCh— Cl bond is split in the mixed-function oxidase system of the hepatocytes. After this cleavage damage may occur directly from the free radicals (-CCl and -Cl) and/or from the formation of toxic metabolites such as phosgene." ... 

Carbon tetrachloride was fetotoxic to rats when administered on days 6-15 of gestation at 300 or 1000 ppm, 7 hours/day an increase in skeletal anomalies due to delayed development was observed in the offspring. Signs of maternal toxicity included weight loss and hepatic damage. ... 

Liver or kidney damage Toluene, and carbon tetrachloride, 1,1,2-2-tetrachloroethane, chloroform... 

The liver is especially sensitive to carbon tetrachloride. In mild cases, the liver becomes swollen and tender, and fat builds up inside the organ. In severe cases, liver cells may be damaged or destroyed, leading to a decrease in liver function. Such effects are usually reversible if exposure is not too high or too long. 

After exposure to high levels of carbon tetrachloride, the nervous system, including the brain, is affected. Such exposure can be fatal. The immediate effects are usually signs of intoxication, including headache, dizziness, and sleepiness perhaps accompanied by nausea and vomiting. These effects usually disappear within a day or two after exposure stops. In severe cases, stupor or even coma can result, and permanent damage to nerve cells can occur. 

Exposure of rats to carbon tetrachloride (up to 160 mg/kg/day for 10 days) by gavage did not alter the primary antibody response to sheep red blood cells, lymphoproliferative responses to mitogen or mixed leukocytes, natural killer cell activity, or cytotoxic T lymphocyte responses also, spleen and thymus weights were comparable to controls (Smialowicz et al. 1991). In rats exposed twice weekly for 4-12 weeks to 3,688 mg/kg/day, there was histologic evidence of hemorrhage, hemosiderin deposition, and lymphocyte depletion in the pancreaticoduodenal lymph node (Doi et al. 1991), an effect which may be secondary to induced hepatic damage. 

Cardiovascular Effects. Inhalation and oral studies in humans and animals have not revealed any treatment-related histopathological lesions of heart tissue, or impairment of cardiac functions, even at dose levels causing severe liver and kidney damage (Adams et al. 1952 Stewart et al. 1961 Umiker and Pearce 1953). It is possible that high-level carbon tetrachloride exposure may produce cardiac arrhythmias by sensitization of the heart to catecholamines (Reinhardt et al. 1971). Accordingly, there is some concern for cardiovascular toxicity following substantial exposure to carbon tetrachloride. 

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