[Show abstract][Hide abstract] ABSTRACT: Different properties of water insoluble heterocyclic compounds such as quinazolinones, with various biological and pharmacological properties (anti-bacterial, anti-inflammation, sedation, antidepression) are also used for the treatments of cancer and HIV. Our previous results proved that two new derivatives of quinazolinones are toxogenic and teratogenic chemicals for embryos. Pregnant Balb/C mice (n=25) were divided into 4 groups of control,receiving distilled water, sham,treated with 0.05% methyl cellulose (the solvent)and two experimental groups 1 and 2, receiving one of the most effective dose of 100mg/kg/body weight of 4(3H)quinazolinone-2-propyl-2-phenyl ethyl(QPPE)and 4(3H)quinazlonones-2-ethyl-2-phenyl ethyl (QEPE), by IP injections, on one of the most effective day 8 of gestation. After anesthetising mothers, brains, stomachs, hearts and spleens of 4-day old newborn Balb/C mice were removed, fixed and stained with H & E for light microscopic and quatitative studies. Pathological observations demonstratded an increase in the number of astrocytes of cerebral cortex and medulla of newborn mice of treated groups. Comfirming the results, one-way ANOVA,LSD and chi square tests (*P<0.05) showed no significant differences between the morphology of newborn mice of control, sham and treated groups'astrocytes, but there were significant differences in the number of astrocytes of newborn mice of groups treated with QPPE and QEPE. Results showed symptoms of gastritis (hyperaemia and decrease in thickness of mucus layer) in newborn Balb/C mice of treated groups. Quinazolinones also created necrotic cells and an increase in connective tissues of hearts of newborn mice of treated groups, but there were no significant differences amongst newborn mice of QPPE and QEPE treated groups. Statistical data indicated significant differences between thickness of capsules and number of macrophage cells of spleens of experimental groups, in comparison with sham and control groups. In conclusion: 1)Astrocyte hyperplasia decrease toxic effects of QPPE and QEPE,by passing through blood-brain barrier;2)Oxygen-derived free radicals play pathological roles in gastritis and radical scavengers such as alfa tocopherol. Carotenoids glutathione redox system also plays a significant role in protecting membranes from oxidative damages;3)By having no active chemical groups and production of active groups and free radicals, after being affected by cytochrome P450 and metabolized in heart, release of intracellular components (such as lysosomal enzymes and lipid peroxidation), cells, organelles, membranes injuries and myocyte necrosis happen;4)Appearance of connective tissues, between myocytes,is due to the stimulation of multiplication of fibroblasts because of necrosis and their annihilation;So,necrotic cardiac cells will be replaced by connective tissues and 5)Damages observed in newborn mice livers, intestines, kidneys, hearts, stomachs and brains,in previous and this report, could have been the reason why the number of macrophage cells have been increased in spleens.Some studies reported damages to the organs such as livers and hearts can cause an increase in the thickness of spleen capsule, consequently, its weight and length.
Full-text · Article · Jan 2010 · Pharmacologyonline