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Hepatotoxic effects of CCl4 on English sole (Parophrys vetulus): possible indicators of liver dysfunction.

Selected serum parameters (enzyme activities and triglycerides) and liver glutathione and vitamin C concentrations were measured in English sole (Parophrys vetulus) after i.p. injection of carbon tetrachloride (CCl4), a hepatotoxin in fish. Serum lactate dehydrogenase (LDH), alkaline phosphatase (AP) and glutamate dehydrogenase (GDH) activities and the concentration of triglycerides increased in a dose-dependent manner 24 hr post injection. Concentrations of glutathione (reduced and oxidized) and ascorbic acid (vitamin C) in liver did not change in response to CCl4 toxicity 24 hr post injection. These studies indicate that serum AP activity and triglyceride concentrations can be useful in assessing the effects of CCl4-induced liver toxicity in this species of marine fish. Serum LDH and GDH activity should be used with some caution in assessing liver damage in English sole, as other tissues represent more likely sources for serum activity. The levels of liver antioxidants do not appear to be significantly affected, 24 hr post injection, by this particular hepatotoxin.

Alkaline Phosphatase↗

Effect of alcohol on viral hepatitis and other forms of liver dysfunction.

Alcohol is a known hepatotoxic agent, which may exacerbate liver injury caused by other agents. The wide prevalence of alcohol use and abuse in society makes it an important cofactor in many other liver diseases. Examples of liver diseases that are significantly influenced by ingestion of alcohol include chronic viral hepatitis, disorders of iron overload, and obesity-related liver disease.

Comorbidity↗

The potential of bone marrow stem cells to correct liver dysfunction in a mouse model of Wilson's disease.

Metabolic liver diseases are excellent targets for correction using novel stem cell, hepatocyte, and gene therapies. In this study, the use of bone marrow stem cell transplantation to correct liver disease in the toxic milk (tx) mouse, a murine model for Wilson's disease, was evaluated. Preconditioning with sublethal irradiation, dietary copper loading, and the influence of cell transplantation sites were assessed. Recipient tx mice were sublethally irradiated (4 Gy) prior to transplantation with bone marrow stem cells harvested from normal congenic (DL) littermates. Of 46 transplanted tx mice, 11 demonstrated genotypic repopulation in the liver. Sublethal irradiation was found to be essential for donor cell engraftment and liver repopulation. Dietary copper loading did not improve cell engraftment and repopulation results. Both intravenously and intrasplenically transplanted cells produced similar repopulation successes. Direct evidence of functionality and disease correction following liver repopulation was observed in the 11 mice where liver copper levels were significantly reduced when compared with mice with no liver repopulation. The reversal of copper loading with bone marrow cells is similar to the level of correction seen when normal congenic liver cells are used. Transplantation of bone marrow cells partially corrects the metabolic phenotype in a mouse model for Wilson's disease.

Animals↗

[Is MAC effected by liver dysfunction?--Bilirubin and MAC].

If MAC is decreased in patients with liver injury, the amount of inhaled anesthetic administered to these patients could be reduced, and thereby reducing the impact of the anesthetic in such patients. The effect of jaundice in liver injury on halothane MAC was investigated in this study. After MAC for control was determined, 12 mongrel dogs received ligation of the common bile duct (CBD). MAC determination followed 1, 2, and 3 weeks after CBD ligation in 6 dogs in experiment 1. The other 6 dogs received bilirubin i.v. 1 week after CBD ligation, and MAC was determined before and after bilirubin, i.v. in experiment 2. Halothane was the only anesthetic used throughout the studies. In experiment 1, serum total bilirubin (TBil) increased to 7mg.d1-1; bilirubin did not enter the cerebro-spinal fluid (CSF); and MAC did not decrease significantly. In experiment 2, TBil increased to 21mg.dl-1; bilirubin entered the CSF; MAC significantly decreased 15% from control; and the correlation between MAC decrease and TBil increase was statistically significant (P less than 0.05). The results suggest that increase in serum bilirubin in liver injury will decrease MAC.

Anesthesia, Inhalation↗

[Liver dysfunction associated with total parenteral nutrition].

An evaluation is made of liver malfunctions in patients receiving TPN over a period of > or = 15 days between 1989 and 1991. Use was made of the monitoring records on patients undergoing TPN and, subsequently, of clinical records, with analysis of diagnoses and type of intervention, the biochemical parameters (SGOT, SGPT, GGT, FA, LDH, and total and direct bilirubin), and the type and degree of malnutrition, nutritional backup, associated medication, etc. A group of patients was excluded from the study on the basis of the following criteria: liver-biliary disease, cardiac insufficiency, liver metastasis, sepsis, kidney insufficiency and hepatotoxic drugs. Of 237 patients, 75 (31.64%) had liver alterations: following application of the exclusion criteria, 24 patients (10.12%) were taken with liver alterations attributable to the TPN. Macro- and micronutrients were included in the TPN. We found no relation between the kcal/kg of weight, nor with the quantity of glucose and fats nor of nitrogen, calculated according to individual requirements: they remained within the limits established. No serious case of cholestatic jaundice was encountered. Moderate to severe malnutrition was found in 50% of patients, so that this must be treated as a risk factor. GGT is the first enzyme to alter; this occurred in the largest proportion of patients (91.66%), followed by SGPT. FA and GOT are altered in the same percentage of patients. Biochemical parameter monitoring is essential in patients undergoing TPN, not only for appraisal of the nutritional state but also to prevent or correct potential serious metabolic complications.

Adult↗

Etiology of jejunoileal bypass-induced liver dysfunction in rats.

Several recent studies suggest that jejunoileal bypass-induced liver disease results from malabsorption of essential nutrients. However, in experimental animals, resection of the defunctionalized bowel substantially reduces bypass-induced liver injury. Such models are often used to support the theory that bacteria in the defunctionalized bowel produce toxic substances which result in liver damage. We used a rat model to first explore the effects of intestinal bypass vs resection on various parameters of liver injury, and subsequently compared these findings to the effect of both bypass and resection on mucosal adaptation in the remaining intact bowel after each procedure. Bypassed animals had lower levels of hepatic cytochrome P-450, glucose-6-phosphatase, pentobarbital hydroxylase, and serum triglycerides than did animals undergoing resection of defunctionalized bowel. Concurrently, resected animals had much greater increases in mucosal weight, DNA content, and protein content in the intact bowel than did bypassed animals. We speculate that the beneficial effects of resection of bypassed bowel on liver function may be a result of increased mucosal hyperplasia in resected animals, rather than elimination of production of toxic substances in the defunctionalized bowel.

Animals↗

Anesthesia for severe liver dysfunction.

By using these guidelines, we have safely anesthetized high-risk liver patients with minimal complications. By understanding the consequences of the underlying disease, prudent selection of agents that use alternate methods of excretion, careful perioperative support and management, and close observation during the postoperative period, the liver disease patient may be safely anesthetized with minimal complications.

Anesthesia↗