Ethanol toxicity

Some toxicants that affect body temperature are shown in Figure 6.11. Among those that increase body temperature are benzadrine, cocaine, sodium fluoroacetate, tricyclic antidepressants, hexachlorobenzene, and salicylates (aspirin). In addition to phenobarbital and ethanol, toxicants that decrease body temperature include phenothiazine, clonidine, glutethimide, and haloperidol. 

Important characteristics of zero-order reactions are that (1) a constant amount of drug is eliminated per unit time since the system is saturated (maximized) and (2) the half-life is not constant for zero-order reactions but depends on the concentration. The higher the concentration, the longer the half-life. Therefore, the term zero-order half-life has little practical significance since it can change and (3) zero-order kinetics is also known as nonlinear or dose-dependent. For example, if the body can metabolize ethanol at a rate of 10 ml per hour, then if one consumes 60 ml, it will take 3 hours to metabolize half of it (the half-life under these circumstances). However, if 80 ml is consumed the half-life will now become 4 hours. This is particularly significant regarding ethanol toxicity. 

Thirunavukkarasu, V., Anuradha, C.V. and Viswanathan, P. (2003) Protective effect of fenugreek (Trigonella foenum-graecum) seeds in experimental ethanol toxicity. Phytotherapy Research 1 7(7), 737-743. 

The mainstay of medical treatment of patients with ethanol toxicity is supportive care. In general, a conservative approach is recommended for ethanol intoxication. Supportive therapy for overdose may include treatment for respiratory depression, hypotension, and altered glucose or thiamine levels. If the ingestion occurred within one hour of presentation, placing a nasogastric tube and evacuating the stomach contents can prove helpful. In patients with chronic ethanol abuse, therapy may include administration of thiamine to prevent neurologic injury. The administration of medications to cause emesis is not recommended because of the rapid onset of CNS depression as well as aspiration risks. 

Animal toxicity corresponds to ethanol toxicity in humans. 

Another mechanism of ethanol toxicity involves oxidative stress. Ethanol-induced liver disease is associated with significant oxidative stress as well as with increased levels of iron, which is also known to initiate oxidative stress in the liver. The combined oxidative stress induced by ethanol and iron greatly increases results in lipid peroxidation and the production of aldehydes such as 4-hydroxy-2-nonenal, compounds that have... 

Acute and chronic ethanol administration or intake and its subsequent withdrawal in experimental animals and in humans exert major effects on tryptophan and serotonin metabolism. The serotonin status is disturbed in animal models of alcoholism and in alcohol-dependent patients characterized by a higher preference for alcohol consumption. A few experimental studies have suggested that some aspects of ethanol toxicity may be improved by the administration of tryptophan.108109 These preliminary findings suggested the possibility of a beneficial effect of added tryptophan on hepatic protein synthesis in ethanol-treated rats, but whether tryptophan administration may be of therapeutic value needs to be established by further investigative studies. 

Zidenberg-Cherr S, Hurley ES, Eonnerdal B, et al. 1985. Manganese deficiency Effects on susceptibility to ethanol toxicity in rats. J Nutr 115 460-467. 

Studies on mice showed that certain organic zinc salts, such as aspartate, orotate, histidine, and acetate, alone or in conjunction with thiols, exhibited protective action against ethanol toxicity (Floersheim 1987). Corresponding Mg, Co, Zr, and Li salts showed similar action. Experimentation reduced lipid peroxides produced in the liver in chronic ethanol toxicity (Marcus et al. 1988). Vitamin E may have an antidotal action against alcohol toxicity. V-Acetylcysteine [616-91-1] is reported to combat ethanol-acetaminophen toxicity (Carter 1987). 

Floersheim, G. L. 1987. Synergism of organic zinc salts and sulfhydryl compounds (thiols) in the protection of mice against acute ethanol toxicity and protective effects of various metal salts. Agents Actions 27(1-2) 217-22 cited in Chem. Abstr. CA 707(19) 17041 le. 

Pollard, M. E. 1988. Enhancement of ethanol toxicity by caffeine evidence of synergism. Biochem. Arch. 4(2) 117-24 cited in Chem. Abstr. CA 109(1) 50107e. 

C. Ingestion. Reported fatal doses vary from 200 mg to more than 20 g of iodine an estimated mean lethal dose is approximately 2-4 g of free iodine. USP iodine tincture contains 100 mg iodine per 5 mL, and strong iodine tincture contains 350 mg of iodine per 5 mL. Iodine ointment contains 4% iodine. Consider ethanol toxicity with large exposures (see p 190). 

MTS assays of IEC-6 cells after exposure to 100-1000 ig/ml Hf-PS or Hf-PS-1 showed no cytotoxicity (Fig. 11.9). Furthermore, Hf-PS-1, but not Hf-PS, appeared to protect against ethanol-induced C5 otoxicity (Fig. 11.10A). When cell viability assays were performed on cells after exposure to 0-500 rg/ml Hf-PS-1 for 3-24 h followed by exposure to 5% ethanol for 1 h, Hf-PS-1 was found to have a concentration- and time-dependent protective effect (Fig. ll.lOB). Results of MTS assays showed that ethanol treatment induced the death of the IEC-6 cells and that pretreatment with Hf-PS-1 for 6-24 h coimteracted this effect. Morphological studies also confirmed protection against ethanol toxicity by Hf-PS-1. Ethanol treatment induced cell shrinkage and decreased the number of viable cells (Fig. 11.11), but Hf-PS-1 pretreatment inhibited this damage. These results indicate that Hf-PS-1 pretreatment is protective against ethanol-induced cell death. 

Moreover, GSH levels were observed to determine if Hf-PS-1 influenced the effect of ethanol metabolism on cellular redox status. Since a Western blot analysis demonstrated the activation of JNK by ethanol, the relationship between ethanol toxicity and JNK activation using the JNK inhibitor SP600125 was examined and found that ethanol treatment decreased GSH levels to 72.72% ( 14.84%) of the control level, but cotreatment with ethanol and either Hf-PS-1 or SP600125 increased GSH levels to 118.18% ( 10.49%) or 95.45% ( 9.09%), respectively, of the control level (Pig. 11.14). These results suggest that Hf-PS-1 protects against ethanol-induced damage by inhibiting JNK phosphorylation and that JNK plays an important role in ethanol-induced toxicity. 

The signaling pathways related to the ethanol-protective effect of Hf-PS-1 in IEC-6 cells. Ethanol induced the death of IEC-6 cells in a dose-dependent marmer, and pretreatment with Hf-PS-1 abrogated the ethanol toxicity. When examined whether the effect of Hf-PS-1 on ethanol cytotoxicity was associated with IGF-IR signaling pathways, involving MAPK, it was found that ethanol treatment decreased the phosphorylation of She and the binding of Grb2 to She, and Hf-PS-1 pretreatment... 

Stress tolerance (primarily caused by temperature, osmotic pressure, ethanol toxicity or hydrostatic pressure in CCVs)... 

The causes of sluggish and stuck fermentations include fermentation at temperature extremes, nutritional deficiencies, osmoregulation, ethanol toxicity, and in low-temperature fermentations, long-term anaerobiosis. To these classically ascribed sources can be added failures in adequately preparing yeast starters as well as the presence of inhibitory compounds which may include pesticides and those produced by microorganisms. 

Orotic acid and lysine orotate decrease ethanol toxicity [401,402]. 

T7 Thomas, H. M. Inhibition of ethanol toxicity by lysine orotate (ORL). FEES Lett., 7, 291-292 (1970)... 

Gimenez et al. (1968) described 28 children with ethanol toxicity from percutaneous absorption. In Argentina, a popular procedure was to apply ethanol-soaked cloths to the abdomens of babies as a home remedy for the treatment of disturbances of the GI tract, such as cramps, pain, vomiting and diarrhea, or because of... 

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