Search results for "TOXICITY"
showing 10 items of 2261 documents
Synthesis and pharmacological evaluation of 1-methyl-5- [substituted-4(3H)-oxo-1,2,3-benzotriazin-3-yl]-1H-pyrazole-4-acetic acid derivatives
1998
Several new 1-methyl-5-[substituted-4-oxo-1,2,3-benzotriazin-3-yl] -1H-pyrazole-4-acetic acids and their ethyl ester derivatives were prepared. The compounds were tested for analgesic and antiinflammatory activities, acute toxicity, ulcerogenic effect, and as in vitro inhibitors of 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD), since it is claimed that the inhibition of such an enzyme predicts in vivo antiinflammatory activity. Some compounds were more active than phenylbutazone in the phenylbenzoquinone and acetic acid peritonitis tests, and equiactive to the same drug in the carrageenin paw edema test. All the compounds inhibited the 3 alpha-HSD, but no correlation was observed with …
Gender differences in the effects of haloperidol on avoidance conditioning in mice
1995
Abstract Gender differences in the effects of haloperidol (0.07S mg/kg per day for 5 days) on avoidance conditioning were evaluated. We also studied performance of the subjects free of the drug and the acute effects of haloperidol in animals trained without drug 48 h after the last haloperidol administration. Latencies of escape and avoidance responses, number of nonresponses, escapes, avoidances, crossings during the adaptation period, crossings during intertrial intervals, and total crossings per minute were analyzed. This dosage impaired conditioning of the male animals but did not attain the same effects on females. Haloperidol did not deteriorate performance of the task when it had bee…
Influence of GSM signals on human peripheral lymphocytes: study of genotoxicity.
2013
Exposure to radiofrequency (RF) electromagnetic fields (EMF) is continuously increasing worldwide. Yet, conflicting results of a possible genotoxic effect of RF EMF continue to be discussed. In the present study, a possible genotoxic effect of RF EMF (GSM, 1,800 MHz) in human lymphocytes was investigated by a collaboration of six independent institutes (institutes a, b, c, d, e, h). Peripheral blood of 20 healthy, nonsmoking volunteers of two age groups (10 volunteers 16-20 years old and 10 volunteers 50-65 years old) was taken, stimulated and intermittently exposed to three specific absorption rates (SARs) of RF EMF (0.2 W/kg, 2 W/kg, 10 W/kg) and sham for 28 h (institute a). The exposures…
Rat liver endothelial and Kupffer cell-mediated mutagenicity of polycyclic aromatic hydrocarbons and aflatoxin B1.
1990
The ability of isolated rat liver endothelial and Kupffer cells to activate benzo(a)pyrene (BP), trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene (DDBP), trans-1,2-dihydroxy-1,2-dihydrochrysene (DDCH), and aflatoxin B1 (AFB1) to mutagenic metabolites was assessed by means of a cell-mediated bacterial mutagenicity assay and compared with the ability of parenchymal cells to activate these compounds. Endothelial and Kupffer cells from untreated rats were able to activate AFB1 and DDBP; DDBP was activated even in the absence of an NADPH-generating system. Pretreating the animals with Aroclor 1254 strongly enhanced the mutagenicity of the dihydrodiol, whereas the mutagenicity of AFB1 showed a sligh…
Interspecies differences in cancer susceptibility and toxicity.
1999
One of the most complex challenges to the toxicologist represents extrapolation from laboratory animals to humans. In this article, we review interspecies differences in metabolism and toxicity of heterocyclic amines, aflatoxin B1, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and related compounds, endocrine disrupters, polycyclic aromatic hydrocarbons, tamoxifen, and digitoxin. As far as possible, extrapolations to human toxicity and carcinogenicity are performed. Humans may be more susceptible to the carcinogenic effect of heterocyclic amines than monkeys, rats, and mice. Especially, individuals with high CYP1A2 and 3A4 activities and the rapid acetylator phenotype may be expected to have …
Gender and age-dependent differences in the mitochondrial apoptogenic pathway in Alzheimer's disease
2008
Age-related mitochondrial oxidative stress is highly gender dependent. The aim of this study was to determine the role of gender in the mitochondrial contribution to neuronal apoptosis in Alzheimer's disease (AD). We used mitochondria isolated from brains of Wistar rats to study the toxicity of ss-amyloid peptide (Ass), and found that it increases mitochondrial peroxide production, nitration and oxidation of proteins, and release of cytochrome c. The toxic effects occurred in young males and in old females but not in young females, indicating their resistance to Ass. This resistance was abolished with age. These toxic effects of Ass were prevented by heme. Our findings provide a molecular m…
Long-term effects on cortical glutamate release induced by prenatal exposure to the cannabinoid receptor agonist (r)-(+)-[2,3-dihydro-5-methyl-3-(4-m…
2003
The aim of the present in vivo microdialysis study was to investigate whether prenatal exposure to the CB1 receptor agonist WIN55,212-2 mesylate (WIN; (R)-()-(2,3- dihydro-5-methyl-3-(4-morpholinyl-methyl)pyrrolo(1,2,3-de)- 1,4-benzoxazin-6-yl)-1-naphthalenylmethanone), at a dose of 0.5 mg/kg (s.c. from the fifth to the 20th day of gestation), that causes neither malformations nor overt signs of toxicity, influences cortical glutamate extracellular levels in adult (90- day old) rats. Dam weight gain, pregnancy length and litter size at birth were not significantly affected by prenatal treatment with WIN. Basal and K-evoked dialysate glutamate levels were lower in the cerebral cortex of adul…
Effect of gender on mitochondrial toxicity of Alzheimer's Abeta peptide.
2007
The aim of this article is to review the role of mitochondria in the pathogenesis of Alzheimer's disease. Additionally, the effect of gender on the incidence of Alzheimer's disease and the pathophysiological mechanisms involved will be discussed. Mitochondria, in the presence of Alzheimer's amyloid-beta peptide, increase the formation of reactive oxygen species which act both as damaging agents and also as signaling molecules. These radicals, in fact, unleash a mechanism involving the liberation of cytochrome c that leads to neuronal apoptosis. Notably, young females appear protected against the mitochondrial toxicity of amyloid-beta, likely due to the upregulation of antioxidant enzymes wh…
Xenobiotic metabolizing enzymes of rat liver nonparenchymal cells.
1986
Abstract The nonparenchymal cells (NPC) of the liver are primarily located along the sinusoids and therefore are the first cells to encounter blood-borne xenobiotics. To study the possible role of the NPC in the metabolism of xenobiotics, populations of NPC and parenchymal cells (PC) were prepared from rats and various xenobiotic metabolizing enzyme activities investigated. The specific activity of every enzyme studied (ethoxyresorufin deethylase, benzphetamine demethylase, glutathione transferase, UDP glucuronosyltransferase, and microsomal epoxide hydrolase) was 12 to 1000% higher in the PC than in the NPC populations and the patterns of activities between the two populations were remarka…
Long-term effects of commercial and congeneric polychlorinated biphenyls on ethane production and malondialdehyde levels, indicators of in vivo lipid…
1988
Ethane exhalation was increased in male Sprague-Dawley rats following a single intraperitoneal (IP) injection of Aroclor 1254 (500 mg/kg). In the first 2 weeks following Aroclor 1254 treatment, the increase in ethane exhalation was due to an inhibition of metabolism of endogenous ethane rather than to an increase in ethane production. In weeks 3 and 4 following Aroclor 1254 administration, metabolic clearance of ethane returned to and exceeded control levels, while ethane production increased to approximately twice the control rates (day 30). The HPLC determination of in situ hepatic malondialdehyde levels revealed a 2-fold increase in malondialdehyde content on day 30 following the Aroclor…