Showing papers in "Drug Metabolism Reviews in 1988"
TL;DR: In this paper, Flavin-containing monooxygenases: Catalytic mechanism and substrate specificities are discussed. But the authors focus on the mechanism and not the substrate.
Abstract: (1988). Flavin-containing monooxygenases: Catalytic mechanism and substrate specificities. Drug Metabolism Reviews: Vol. 19, No. 1, pp. 1-32.
341 citations
TL;DR: The present study focused on the binding and transport of Hormones and Xenobiotics by Glutathiones-Transferases, a type of “cell reprograming”, which has shown promise in understanding the mechanism behind drug resistance.
Abstract: (1988). Intracellular Binding and Transport of Hormones and Xenobiotics by Glutathiones-Transferases. Drug Metabolism Reviews: Vol. 19, No. 3-4, pp. 305-318.
252 citations
TL;DR: The metabolic activation of nitroheterocyclic therapeutic agents was studied in this paper, where it was shown that the activation of these agents can be traced to the presence of nitrogen.
Abstract: (1988). The metabolic activation of nitroheterocyclic therapeutic agents. Drug Metabolism Reviews: Vol. 19, No. 1, pp. 33-62.
114 citations
TL;DR: In this paper, the design and bioactivation of presystemically stable prodrugs is discussed. But the authors focus on the design of a prodrug and not on its bioactivation.
Abstract: (1988). The design and bioactivation of presystemically stable prodrugs. Drug Metabolism Reviews: Vol. 19, No. 2, pp. 165-194.
95 citations
TL;DR: The gut bacteria produce acids which can lower lumenal pH and, in turn, modify bacterial enzyme activities, however, the changes in activity appear to be enzyme specific, some increasing with pH and others being inversely related to pH of incubation.
Abstract: (1988). Factors Affecting Metabolic Activity of the Intestinal Microflora. Drug Metabolism Reviews: Vol. 19, No. 3-4, pp. 243-261.
82 citations
48 citations
TL;DR: Assessment of mortality data from modern-day bioassay studies indicates that low-dose animal exposure to a variety of toxic agents can, through an unknown mechanism, also induce beneficial changes which promote health and prolong life (longevity hormesis).
Abstract: (1988) Hormesis, gompertz functions, and risk assessment Drug Metabolism Reviews: Vol 19, No 2, pp 195-229
33 citations
TL;DR: It was demonstrated (in certain cases) that longevity hormesis could enhance lifespan, even in the presence of concomitant toxicity, even when toxicity was evident, hormesiscould ameliorate some of the mortality.
Abstract: Based on the proposition that the logarithm of age-specific mortality rate (Gompertzian) is a linear measure of the mean intensity of injury for a homogeneous mammalian population in a uniform environment, a model was developed which characterizes mortality experience resulting from both toxic and hormetic actions. The mortality-reducing component (longevity hormesis) was assumed to be reversible; toxic effects, on the other hand, were assumed to accumulate irreversibly. Following chronic low-dose administration of selected toxic substances, it was demonstrated (in certain cases) that longevity hormesis could enhance lifespan, even in the presence of concomitant toxicity. Even when toxicity was evident, hormesis could ameliorate some of the mortality. The assumption that high-dose chronic toxicity studies can generate realistic estimates of risk at low doses is challenged.
27 citations
24 citations
TL;DR: New techniques employing microlight guides allow metabolic events to be studied noninvasively in tiny volumes of liver tissue located in defined regions within the liver lobule to monitor native fluors which are metabolically linked and nonfluorescent substrates which are converted to fluorescent products by specific enzyme systems.
Abstract: New techniques employing microlight guides allow metabolic events to be studied noninvasively in tiny volumes of liver tissue located in defined regions within the liver lobule. These events include oxygen utilization, carbohydrate metabolism, ethanol oxidation, monooxygenation, glucaronidation, and sulfation. Two-fiber microlight guides are constructed from 80-microns optical fibers and are placed on periportal or pencentral regions of the liver lobule based on the pattern of liver pigmentation. Light of selected wavelengths is transmitted to the liver surface by one fiber, and the resultant fluorescence or reflectance is delivered to a photomultiplier by the second fiber. The experimental strategy is to monitor native fluors which are metabolically linked (e.g., NADH) or to infuse nonfluorescent substrates which are converted to fluorescent products by specific enzyme systems (e.g., 7-ethoxycoumarin for monooxygenation). Alternatively, disappearance of fluorescence can also be employed (e.g., 7-hydroxycoumarin for sulfation or glucuronidation). With these methods, rate-limiting steps in situ (e.g., substrate uptake, enzyme activity, cofactor supply) have been studied for several metabolic systems in periportal and pericentral regions of the liver lobule.
18 citations
TL;DR: Using electron spin resonance (ESR), it was observed that soon after the AZQ free radical appeared, it decayed and was replaced by a doublet with ESR parameters that suggested the presence of the ascorbyl radical (AH), which was confirmed by adding exogenous ascorbic acid toAZQ free radicals generated by a suspension of L1210 murine leukemia cells.
Abstract: Diaziquone (AZQ) is a quinone-containing alkylating agent undergoing trials as an antitumor drug. The quinone moiety of this compound places it among a group of compounds whose activity is believed to be modulated by a redox cycle that activates the compounds to their free radicals (e.g., adriamycin). AZQ is unique among these compounds in that it can be reduced to its free radical (AZQH) by a variety of cells in culture, including human and murine cancer cells. Red blood cells (RBC) were also observed to reduce AZQ to its free radical. Using electron spin resonance (ESR), we observed that soon after the AZQ free radical appeared, it decayed and was replaced by a doublet with ESR parameters that suggested the presence of the ascorbyl radical (AH). The identity of AH was confirmed by adding exogenous ascorbic acid to AZQ free radicals generated by a suspension of L1210 murine leukemia cells. The endogenous ascorbic acid was shown to arise mostly from the "buffy coat" of an RBC preparation which contained leukocytes. Leukocytes are second only to the adrenals in level of ascorbic acid in humans. Cyclic voltammetry of ascorbic acid, AZQ, and adriamycin in Hank's Balanced Salt Solution (HBSS pH 7.5), the buffer used for biological measurements, showed that the oxidation peak potential for ascorbic acid (Eap = +0.43 V) is closer to the reduction peak potential for AZQ (Ecp = -0.36 V) than that for adriamycin (Ecp = -0.67 V). This may explain why the ascorbic acid redox system interacts with that of AZQ but not with that of ADR.
TL;DR: The Disposition of Hexobarbital: 15 years of an intriguing model substrate as discussed by the authors, which is an interesting model substrate for hexobarsenal and hexobarbinar.
Abstract: (1988). Disposition of hexobarbital: 15 years of an intriguing model substrate. Drug Metabolism Reviews: Vol. 19, No. 2, pp. 109-164.
TL;DR: It is expected that in the coming decade drug metabolism research in China will be carried out at much higher levels with more interesting results.
Abstract: In the past 30 years, the study of drug metabolism in China has followed a zigzag path, from the initial uprising stage to devastation, and then to regeneration. In the reviving decade of 1976-1985, studies have extended to various aspects of the field of drug metabolism and pharmacokinetics. There are rapid increases both in modern facilities and trained personnel. Therefore, it is expected that in the coming decade drug metabolism research in China will be carried out at much higher levels with more interesting results.