Liver slices

Houston JB, Carlile DJ. Prediction of hepatic clearance from microsomes, hepa-tocytes, and liver slices. Drug Metab Rev 1997 Nov 29(4) 891-922. 

Togashi, H., Shinzawa, H., Wakabayashi, H., Nakamura, T., Yong, H., Yamada, N., Ukai, K., Okuyama, Y., Takahashi, T. and Ishikawa, M. (1990). Superoxide is involved in the pathogenesis of paraquat-induced injury in cultured rat liver slices. Hepatology 14, 707-714. 

McLean, A. and Nuttal, L. (1978). An in vitro model of liver injury using paracetamol treatment of liver slices and prevention of injury by some antioxidants. Biochem. Pharmacol. 27, 425-430. 

In rat liver slices, evidence also supports the roles of QMs in mediating the toxicity of a series of 4-methylphenols.24 The potency correlates with rates of QM formation in the order 2-bromo-4-methylphenol > 4-methylphenol = DMP > TMP > 2-methoxy-4-methylphenol. None of these compounds contain two bulky ortho substituents, so as discussed earlier the corresponding QMs are expected to be highly reactive. The authors suggested that differences in the reactivities of these QMs determine their relative toxic potencies as electron-donating substituents on the ring stabilize the QM and thereby reduce its toxicity (e.g., 2-methoxy-4-methylphenol is less toxic than DMP) and conversely, electron-withdrawing substituents destabilize QMs and enhance toxicity (e.g., 2-bromo-4-methylphenol is more potent than DMP). 

Thompson, D. C. Perera, K. Krol, E. S. Bolton, J. L. o-Methoxy-4-alkylphenols that form quinone methides of intermediate reactivity are the most toxic in rat liver slices. Chem. Res. Toxicol. 1995, 8, 323-327. 

In the first place, Stadie, Zapp and Lukens67 failed to obtain any evidence for the production of acetic acid or any other steam-volatile acids in liver slices of depancreatized cats. These authors state further that no evidence could be found in the literature for the production of acetic acid in the livers of normal or diabetic animals except for the report of Cook and Harrison.68 They believe that the acetic acid, which... 

The quantity of carbohydrate that is necessary to abolish ketonuria is far less than would be required from an isodynamic standpoint. This is particularly the case with the exogenous ketonuria produced by the administration of acetoacetate. Finally, an in vitro analogy to such a reaction has been found in the ketolytic effect of glycogen on liver slices.81... 

Most of the information on the metabolism of hexachloroethane has been collected by in vitro techniques using rat liver slices or rat liver microsomes. Figure 2-3 summarizes the results of these studies. The identification of tetrachloroethene and pentachloroethane as the initial metabolites of hexachloroethane metabolism in vitro agrees with in vivo data from sheep that were orally exposed to doses of 500-1,000 mg/kg hexachloroethane (Fowler 1969b). 

Harris, J.W., Rahman, A., Kim, B.R., Guengerich, F.P. and Collins, J.M. (1994) Metabolism of taxol by human hepatic microsomes and liver slices participation of cytochrome P450 3A4 and an unknown P450 enzyme. Cancer Research, 54 (15), 4026-4035. 

It will readily be seen in our series of w-fluorocarboxylic acids, that when n is odd, / -oxidation would yield the toxic fluoro-acetic acid, whereas when n is even, the compound would presumably be oxidized only as far as the non-toxic yff-fluoro-propionic acid.1 The pharmacological results obtained are in complete accord with this hypothesis, and provide verification, of a kind not hitherto achieved, of the process of / -oxidation in the living animal body. However, Weinhouse, Medes and Floyd2 have inoculated rat-liver slices with one or two fatty acids containing isotopic carbon, and have obtained some evidence for a process of /7-oxidation. 

An anomaly associated with citrulline that became evident when detailed kinetic studies were made in the 1950s (R.B. Fisher and J.R. Bronk) was the irreproducibility of its catalytic activity in liver slices on the formation of urea, despite the clear evidence from Ratner and Petrack of its importance in arginine synthesis. Initially the discrepancy in catalytic activity between ornithine and citrulline was ascribed to the possible impermeability of the liver cell plasma membrane to the latter intermediate, a hypothesis which was rapidly disproved experimentally. Only recently has it been shown that ornithine transcarbamylase is clearly associated with the ornithine/... 

In vitro studies in our laboratory involving 1-h incubations of 0.5-g liver slices of rainbow trout with 10 ml of 1-, 2.5, and 5-mg/100 ml concentrations of MS-222, resulted in 8.5, 6.9, and k.2% (respectively) of the drug being acetylated. Similar incubations of kidney tissue resulted in 0, 0, and 3.2% acetylation. These incubation studies indicate that the liver is the prime site of acetylation of MS-222, but suggest that some may occur in the kidney as well. However, in vitro evaluation of the acetylating capability of rainbow trout kidney is complicated by the diffuse structure and heavy pigmentation of the organ. 

In our previous studies on the sulfate conjugation of phenols by fish livers, all the liver slices of the test fish and shellfish exhibited sulfate conjugation activities with phenol(14), and among various liver cell fractions separated by ultracentrifugation, only the soluble fraction displayed the sulfate conjugation activity for phenol and various phenolic compounds(15). 

A. Steensma, J. A. Beamand, D. G. Walters, R. J. Price, B. G. Lake, Metabolism of Coumarin and 7-Ethoxy coumarin by Rat, Mouse, Guinea Pig, Cynomolgus Monkey and Human Precision-Cut Liver Slices , Xenobiotica 1994, 24, 893-907. 

Azri-Meehan S, Mata HP, Gandolfi AJ, et al. 1992. The hepatotoxicity of chloroform in precision-cut rat liver slices. Toxicology 73(3) 239-250. 

---