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Inhibition of 2-nitropropane-induced rat liver DNA and RNA damage by benzyl selenocyanate 总被引:5,自引:2,他引:3
We observed that pretreatment of male F344 rats with benzyl selenocyanate,
a versatile organoselenium chemopreventive agent in several animal model
systems, decreases the levels of DNA and RNA modifications produced in the
liver by the hepatocarcinogen 2- nitropropane. To clarify the mechanisms
involved, we pretreated male F344 rats with either benzyl selenocyanate,
its sulfur analog benzyl thiocyanate, phenobarbital or cobalt
protoporphyrin IX; the latter is a depletor of P450. We then determined (1)
the ability of liver microsomes to denitrify 2-nitropropane, (2) effects on
2-nitropropane- induced liver DNA and RNA modifications and (3) amount of
nitrate excreted in rat urine following administration of the carcinogen.
Pretreatment with benzyl selenocyanate or phenobarbital increased the
denitrification activity of liver microsomes by 217 and 765%, respectively,
increased liver P4502B1 by 31- and 435-fold, respectively, decreased the
levels of 2-nitropropane-induced modifications in liver DNA (29-70% and
17-30%, respectively) and RNA (67-85% and 30-50%, respectively), and
increased the 24-h urinary excretion of nitrate by 157 and 209%,
respectively. Pretreatment with benzyl thiocyanate had no significant
effect on any of these parameters. Pretreatment with cobalt protoporphyrin
IX decreased liver P4502B 1 by 87%, decreased the denitrification activity
of liver microsomes by 76%, decreased the 24 h urinary excretion of nitrate
by 88.5%, but increased the extent of 2-nitropropane-induced liver nucleic
acid modifications by 17-67%. These results indicate that the metabolic
sequence from 2-nitropropane to the reactive species causing DNA and RNA
modifications does not involve the removal of the nitro group. Moreover,
they suggest that benzyl selenocyanate inhibits 2-NP-induced liver nucleic
acid modifications in part by increasing its detoxication through induction
of denitrification, although it is evident that other mechanisms must also
be involved.
相似文献
9.
G. Michael Taylor Thomas J. Neuhaus Vanita Shah Susannah Dillon T. Martin Barratt 《Pediatric nephrology (Berlin, Germany)》1997,11(4):404-410
Experimental studies have pointed to charge selectivity as an important determinant of glomerular permeability to macromolecules.
Loss of glomerular basement membrane (GBM) polyanion has been proposed as a cause of the selective proteinuria in minimal
change nephrotic syndrome (MCNS). However, the presence of less-anionic albumin in urine than plasma from MCNS and focal and
segmental glomerulosclerosis (FSGS) patients has been interpreted both as evidence for partial maintenance of charge selectivity
and for involvement of other pathogenic mechanisms. The exact role of charge selectivity in the pathogenesis of nephrotic
proteinuria remains controversial. We have examined the clearance of endogenous proteins of differing size and charge in children
with idiopathic nephrotic syndrome (NS). Chromatofocusing was used to determine the isoelectric points (pIs) of albumins in
paired plasma and urine samples from patients with FSGS (n = 6) and MCNS (n = 6). Charge selectivity was assessed by comparing the pIs of the fractions with the highest albumin concentration (modal
pI) in plasma and urine. The difference between the modal pIs was defined as the delta modal pI. Charge selectivity was also
assessed from the albumin/transferrin and IgG4/IgG1 clearance ratios; size selectivity from the IgG1/albumin and IgG1/transferrin
as well as the IgG4/albumin and IgG4/transferrin clearances. In children with FSGS, the mean (± SD) delta modal pI was – 0.05
± 0.16, and in MCNS – 0.05 ± 0.11. Neither value differed significantly from zero. The albumin/transferrin clearance ratio
showed no significant difference between FSGS and MCNS, but the IgG4/IgG1 clearance ratio was significantly higher in MCNS
(P<0.05). Size selectivity was significantly reduced in FSGS compared with MCNS (for IgG1/transferrin P<0.01 and for IgG1/albumin P<0.05). For IgG4/transferrin and IgG4/albumin, P was <0.05. In conclusion, there was no evidence for residual charge selectivity in idiopathic NS associated with either MCNS
or FSGS during nephrotic-range proteinuria. There was a significant loss of GBM size selectivity in children with FSGS with
heavy proteinuria compared with children with MCNS with heavy proteinuria.
Received August 7, 1996; received in revised form and accepted December 16, 1996 相似文献
10.
Blood platelet uptake of serotonin in episodic aggression 总被引:2,自引:0,他引:2
C S Brown T A Kent S G Bryant R M Gevedon J L Campbell A R Felthous E S Barratt R M Rose 《Psychiatry research》1989,27(1):5-12
Blood platelet uptake of 3H-serotonin (5HT uptake), a potential marker of serotonergic function, was determined in male outpatients with episodic aggression (n = 15) and in age- and sex-matched nonaggressive controls (n = 15). Correlations with rating scales of "impulsivity" (Barratt Impulsivity Scale, 10th revision) and "anger" (Spielberger Anger Expression Scale) were performed. Mean 5HT uptake was 18% lower in patients with episodic aggression. A significant negative correlation between % difference in platelet 5HT uptake and impulsivity score was observed, but the correlation between 5HT uptake and anger was not significant. These results support the hypothesis of disturbed serotonergic function in aggression and suggest that the primary relationship is in the "control" of aggression. The blood platelet may be useful in identifying impulsive subtypes. 相似文献