2,996 research outputs found

    Further studies on the relationship of the stimulatory effects of phenobarbital and 3,4-benzpyrene on hepatic heme synthesis to their effects on hepatic microsomal drug oxidations

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    The administration of either phenobarbital or 3,4-benzpyrene to rats resulted in the rapid and marked induction of [delta]-aminolevulinic acid synthetase (EC 2.3.1.13), the proposed initial and rate-limiting enzyme in the hepatic heme biosynthetic pathway. Enhanced formation of [delta]-aminolevulinic acid was followed sequentially by an enhancement of the liver's capacity to synthesize microsomal heme in vivo, increases in the content of cytochrome P-450 and protoheme in hepatic microsomes and stimulation of certain hepatic microsomal drug oxidations.Changes in the hepatic microsomal levels of cytochrome P-450 paralleled, in part, changes in the activity of hepatic [delta]-aminolevulinic acid synthetase and in the capacity of the liver to synthesize microsomal heme in vivo, suggesting that the rate of hepatic heme synthesis may control the rate of synthesis of hepatic microsomal cytochome P-450. Increases in the hepatic microsomal content of cytochrome b5, however, followed a different time course from that observed from either cytochrome P-450 or protoheme.The simultaneous administration of maximum stimulatory doses of phenobarbital and 3,4-benzpyrene did not result in an additive stimulation of [delta]-aminolevulinic acid synthetase activity, indicating that phenobarbital and 3,4-benzpyrene induce [delta]-aminolevulinic acid synthetase by the same or closely related mechanisms. However, the stimulatory effects of these agents on cytochrome P-450 and on the N-demethylation of 3-methyl-4-monomethylaminoazobenzene were additive, suggesting that differences may exist in the mechanism by which phenobarbital and 3,4-benzpyrene induce hepatic microsomal cytochrome P-450 and enhance certain hepatic microsomal drug oxidations.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/32724/1/0000092.pd

    Stimulation of nuclear protein synthesis in rat liver after phenobarbital administration

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    When a 40 min pulse of leucine-3H was administered to rats 2 hrs after 75 mg/kg of phenobarbital (Pb), there was a 70% increase above control in labeling of microsomal protein and of a nuclear protein fraction extracted with 1 M NaCl. When a 40 min pulse of labeled leucine was given 24 hrs after a single injection of Pb (75 mg/kg), there was a 42% stimulation in the specific activity of microsomal protein but an 87% enhancement, compared to control, in the nuclear protein fraction. Separation of the nuclear fraction on DEAE-cellulose columns indicated that there was a 5-fold stimulation in the specific activity of one of the protein peaks from the nuclear protein fraction of the Pb-treated rats. These data indicate that Pb administration enhances the synthesis of various protein fractions in hepatic cells and suggest that these events may be involved in the enzyme induction produced by this drug.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/32732/1/0000100.pd

    THE EFFECT OF OXEN ON AGRICULTURAL PRODUCTIVITY AND FARM INCOME IN NICARAGUA

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    This study1 uses survey data to assess the effect of oxen as draft animals on agricultural productivity and farm agricultural income in Nicaragua during the year 2017. The results suggest that farms that use oxen to plow the land have higher bean productivity than farms that use stick to plant crops. On average, using oxen increases farm’s bean output by 7.75 100-pound bags, and hiring oxen increases farm’s bean output by 8.5 100-pound bags. Also, using or hiring oxen increases total farm planted area. The main finding about the effect of oxen to plow the land through farm planted area on agricultural farm gross income suggests that using oxen to plow the land increases agricultural farm gross income by 18.13 percent, and that hiring oxen increases agricultural farm gross income by 25.55 percent

    The role of heme synthesis during the induction of hepatic microsomal cytochrome P-450 and drug metabolism produced by benzpyrene

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    [delta]-Aminolevulinic acid synthetase, the initial and rate limiting step in hepatic heme synthesis, is induced by both benzpyrene and phenobarbital. Induction of this enzyme by benzpyrene results in the stimulation of glycine-2-14C incorporation into hepatic microsomal heme in vivo and in the induction of cytochrome P-450 and N-demethylase activity. 3-Amino-1,2,4-triazole, an inhibitor of the second step in hepatic heme synthesis, prevents the stimulation of hepatic heme synthesis and the induction of P-450 and N-demethylase activity. It is suggested that induction of [delta]-aminolevulinic acid synthetase leading to increases in hepatic heme synthesis may be the mechanism by which benzpyrene induces cytochrome P-450 and certain hepatic microsomal oxidations.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/32915/1/0000295.pd

    Pre- and post-initiation modulating effects of green tea ingestion on rat hepatocarcinogenesis

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    The purpose of this study was to investigate the effects of green tea ingestion on hepatocarcinogenesis before and after its initiation. Male Sprague-Dawley rats were fed an AIN76A diet with or without green tea. Initiation was induced by a single dose (200 mg/kg) of diethylnitrosamine at week 4 and 0.02% (w/w) 2-acetylaminofluorene was supplied in the diets. The control group had free access to water for 13 weeks (CTR13). Tea infusion was provided from the beginning of the experiment for 13 weeks (PRE13) or from the post-initiation stage until week 13 (POST13). Three other groups (CTR24, PRE24 and POST24) were added to examine the longer-term effects (24 weeks) with the same experimental design. The percentage area of liver sections that were positive for hepatic placental glutathione S-transferase (GST-P), which was used as a marker of preneoplastic lesions, was smaller in PRE13 (20.2 ± 5.0%, mean ± SD) and POST13 (26.0 ± 4.8%) than in CTR13 (33.2 ± 5.8%, p<0.05). Over the longer period, the GST-P lesions were significantly smaller for both PRE24 and POST24 (21.6 ± 8.5% and 22.2 ± 4.0%, respectively) than for CTR24 (28.6 ± 5.1%, p<0.05), but there was no significant difference between PRE24 and POST24. The liver content of thiobarbituric acid reactive substances was significantly lower in the tea groups than in the controls (p<0.05). However, no significant differences were observed among groups of GST activity. The results show that tea consumption exhibits a stronger short-term initiation-inhibiting ability in liver carcinogenesis, but over a longer period, the preventive effects of green tea ingestion do not differ in post- and pre-initiation

    Sustainable use and commercialisation of bushmeat in Colombia: Toward the operationalization of legal frameworks

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    Key points • Under Colombian law, the sale of game to cover basic needs (e.g. housing, health, education) or to buy other food items is not allowed, since this is considered commercial hunting and does not fall under provisions allowing for subsistence bushmeat hunting. • Law 611 (2000) opened the path to legal commercial use of wildlife. In practice, however, the requirements for obtaining legal permits for commercial hunting activities make it extremely challenging for rural communities to obtain them. • Aware of the role that bushmeat plays in food security, family economy and cultural identity among many rural communities, a number of high-profile Colombian environmental institutions participated in a workshop in 2015 to discuss the operationalisation of the legal framework for the trade in bushmeat by rural communities. • One of the main conclusions of the workshop was that commercial hunting regulations need to legally distinguish between large-scale commercial hunting and the sale of surplus game by subsistence hunters in rural communities. Indeed, these two types of commercial hunting differ in terms of the scale of action, the governance systems in place and the ways in which benefits are equitably distributed among different actors. • The main recommendation was that the regulatory framework should adopt flexible management processes for the local development of sustainable management rules (e.g. list of tradable species, quotas, open seasons, monitoring and evaluation systems). This would allow for the recognition of the specificities of each socio-ecological context, rather than imposing a national-level framework that would likely fail, given Colombia’s diverse biological and cultural characteristics

    Exocyclic amino groups of flanking guanines govern sequence-dependent adduct conformations and local structural distortions for minor groove-aligned benzo[a]pyrenyl-guanine lesions in a GG mutation hotspot context

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    The environmental carcinogen benzo[a]pyrene (BP) is metabolized to reactive diol epoxides that bind to cellular DNA by predominantly forming N(2)-guanine adducts (G*). Mutation hotspots for these adducts are frequently found in 5′- ··· GG ··· dinucleotide sequences, but their origins are poorly understood. Here we used high resolution NMR and molecular dynamics simulations to investigate differences in G* adduct conformations in 5′- ··· CG*GC ··· and 5′- ··· CGG* C··· sequence contexts in otherwise identical 12-mer duplexes. The BP rings are positioned 5′ along the modified strand in the minor groove in both cases. However, subtle orientational differences cause strong distinctions in structural distortions of the DNA duplexes, because the exocyclic amino groups of flanking guanines on both strands compete for space with the BP rings in the minor groove, acting as guideposts for placement of the BP. In the 5′- ··· CGG* C ··· case, the 5′-flanking G · C base pair is severely untwisted, concomitant with a bend deduced from electrophoretic mobility. In the 5′- ··· CG*GC ··· context, there is no untwisting, but there is significant destabilization of the 5′-flanking Watson–Crick base pair. The minor groove width opens near the lesion in both cases, but more for 5′- ··· CGG*C···. Differential sequence-dependent removal rates of this lesion result and may contribute to the mutation hotspot phenomenon

    Radiometric assay for cytochrome P-450-catalyzed progesterone 16[alpha]-hydroxylation and determination of an apparent isotope effect

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    In the course of studies on the oxygenation of steroids by purified P-450 cytochromes, particularly rabbit liver microsomal cytochrome P-450 form 3b, a rapid and reliable radiometric assay has been devised for progesterone 16[alpha]-hydroxylation. In view of the lack of a commercially available, suitably tritiated substrate, [1,2,6,7,16,17-3H]progesterone was treated with alkali to remove the label from potential hydroxylation sites other than the 16[alpha] position. The resulting [1,7,16-3H]progesterone was added to a reconstituted enzyme system containing cytochrome P-450 form 3b, NADPH-cytochrome P-450 reductase, and NADPH, and the rate of 16[alpha]-hydroxylation was measured by the formation of 3H2O. This reaction was shown to be linear with respect to time and to the cytochrome P-450 concentration. An apparent tritium isotope effect of 2.1 was observed by comparison of the rates of formation of tritium oxide and 16[alpha]-hydroxyprogesterone, and the magnitude of the isotope effect was confirmed by an isotope competition assay in which a mixture of [1,7,16-3H]progesterone and [4-14C]progesterone was employed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26627/1/0000168.pd
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