Liver metabolic activity

Ethene at atmospheric concentrations up to 20% was not mutagenic to one strain of Salmonella typhimur-ium with and without liver metabolic activation system (S9). In other strains of Salmonella in the presence and absence of S9, ethene was also negative. Ethene has shown no genotoxic activity in Escherichia coli. In nonbacterial tests, ethene did not induce chromosome aberrations in cultured Chinese hamster ovary cells exposed to 280.5 mgl in the presence and absence of S9, and did not induce micronuclei formation in bone marrow cells of rats or mice exposed up to 3000 ppm for 6 h day 5 days week for 4 weeks. 

Moriya, M., Kato, K. and Shirasu, Y. (1978). Effects of cysteine and a liver metabolic activation system on the activities of mutagenic pesticides. Mut. Res.. 57, 259-263. 

Allemand H, Pessayre D, Descatoire V, et al. 1978. Metabolic activation of trichloroethylene into a chemically reactive metabolite toxic to the liver. J Pharmacol Exp Ther 204 714-723. 

To date, there is very little known about if and how phytochemicals modulate the metabolism of GIT tissues other than the liver. Of particular interest are the xenobiotic metabolizing enzymes of the GIT, which are involved with transformation of drugs and toxins. Whereas the metabolic activities of the resident microflora dominate in the large intestine, mucosal enzyme activities are more important in the small intestine where bacterial densities are lower and the villi and microvilli increase the area of exposure. 

Albano, E., Lott, K.A.K., Slater, T.F., Stier, A., Symons, M.C.R.and Tomasi, A. (1982). Spin trapping studies on the free radical products formed by metabolic activation of carbon tetrachloride in rat liver microsomal fractions, isolated hepato-cytes and in vivo in the rat. Biochem. J. 204, 593-603. 

K. Mizutani, T. Electronic and structural requirements for metabolic activation of butylated hydroxytoluene analogs to their quinone methides, intermediates responsible for lung toxicity in mice. Biol. Pharm. Bull. 1997, 20, 571-573. (c) McCracken, P. G. Bolton, J. L. Thatcher, G. R. J. Covalent modification of proteins and peptides by the quinone methide from 2-rm-butyl-4,6-dimethylphenol selectivity and reactivity with respect to competitive hydration. J. Org. Chem. 1997, 62, 1820-1825. (d) Reed, M. Thompson, D. C. Immunochemical visualization and identification of rat liver proteins adducted by 2,6-di- m-butyl-4-methylphenol (BHT). Chem. Res. Toxicol. 1997, 10, 1109-1117. (e) Lewis, M. A. Yoerg, D. G. Bolton, J. L. Thompson, J. Alkylation of 2 -deoxynucleosides and DNA by quinone methides derived from 2,6-di- m-butyl-4-methylphenol. Chem. Res. Toxicol. 1996, 9, 1368-1374. 

Mitomycin C is an alkylating agent that forms cross-links with DNA to inhibit DNA and RNA synthesis. The pharmacokinetics of mitomycin C are best described by a two-compartment model, with an a half-life of 8 minutes and a terminal half-life of 48 minutes.31 Liver metabolism is the primary route of elimination. Mitomycin C has shown clinical activity in the treatment of anal, bladder, cervix, gallbladder, esophageal, and stomach cancer. Side effects consist of myelosuppression and mucositis, and it is a vesicant. 

The pharmacist should certainly know which drug dosage forms have been designed as delivery systems for prodrugs and also understand the mechanism whereby the active form is made available within the body. Only then can the pharmacist counsel the physician about why a certain product may be inappropriate for such individuals as an achlorhydric patient, a patient with a gastrectomy, or even possibly a patient with a hepatoportal bypass, if liver metabolism... 

Iron appeared to reduce the effects of orally or subcutaneously administered lead on blood enzyme and liver catalase activity (Bota et al. 1982). Treatment of pregnant hamsters with iron- or calcium-deficient diets in conjunction with orally administered lead resulted in embryonic or fetal mortality and abnormalities (ranting, edema) in the litters, while treatment with complete diets and lead did not (Carpenter 1982). Inadequate levels of iron in association with increased body burdens of lead enhanced biochemical changes associated with lead intoxication (Waxman and Rabinowitz 1966). Ferrous iron was reported to protect against the inhibition of hemoglobin synthesis and cell metabolism by lead it has been speculated that iron competes with lead uptake by the cell (Waxman and Rabinowitz 1966). In... 

Chauret, N., Gauthier, A. and Nicoll-Griffth, D.A. (1998) Effect of common solvents on in vitro cytochrome P450 mediated metabolic activities in human liver microsomes. Drug Metabolism and Disposition The Biological Fate of Chemicals, 26, 1-4. 

Muraca, M., Vilei, M.T., Zanusso, G.E., Ferraresso, C., Boninsegna, S., Dal Monte, R., Carraro, P. and Carturan, G. (2002) Si02 entrapment of animal cells Liver-specific metabolic activities in silica-overlaid hepatocytes. Artificial Organs, 26, 664—669. 

Some effects in the liver have been reported, but they may be adaptive changes related to increased metabolic activity. Increased glutathione levels were reported at doses of 70 mg/kg/day for 21 days (Szabo et al. 1977). Because the metabolism of acrylonitrile includes pathways that utilize glutathione (see Section 2.3.3), the higher glutathione levels in the liver may be due to increased demand for glutathione for the metabolism of acrylonitrile. 

A consistent observation in rats exposed to acrylonitrile was increased liver weight, both in acute studies at 65 mg/kg/day (Murray et al. 1978) and chronic studies at 10 mg/kg/day (Bio/dynamics 1980a, 1980b, 1980c). Again, this may be an adaptive change related to increased metabolic activity by the liver due to the presence of acrylonitrile in the body. 

Dwivedi, R.S., G. Kaur, R.C. Srivastava, and C.R.K. Murti. 1985a. Metabolic activity of lysosomes in tin-intoxicated regenerating rat liver. Toxicol. Lett. 28 133-1.118. 

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