components of quinazolinons 4(3H) Quinazolinone-2-Propyl-2-Phenyl Ethyl (QPPE) ... Key words: Biochemistry, mice embryos, quinazolinones toxicities, spleen ...
Current Research Journal of Biological Sciences ISSN © M axwell Scientific Organization, 2010
Histological, Biochemical and Ultrastructures Studies of Embryonic Spleens of Balb/C Mice Treated with Quinazolinones S.L. Maryam, M .T. Daryush and T. Raheleh Developmental Biology , Animal Sciences, Faculty of Biolog ical Sciences, Shahid-Beheshti University (SBU ), G.C.,Tehran, Iran Abstract: Follow ing ou r published reports, the aim of this research was to investigate effects of two new components of quinazolinons 4(3H) Quinazolinone-2-Propyl-2-Phenyl Ethyl (QPPE) and 4(3H) Quinazlonones2-Ethyl-2-Phenyl Ethyl (QEPE), on Balb/C m ice embryos’ spleens, at pathological, biochemical and cellular levels. Balb/C pregnant mice w ere random ly divided into four groups of co ntrol (intact, n=25), sham (n=25), receiving 0/05% /body weight of methyl cellulose (the solvent), and experim ental groups 1 an d 2(n=2 5), receiving the most effective dose, 100mg/kg /body weight of QPPE and QEPE, intraperitoneally. Pregnant mice were anesthetized on day 17,dissected by c-sections, spleens of their embryos were also removed by c-section, fixed and stained with H &E , Reticulin and Trichrom e, hom ogenized for measuremen t of changes in enzym atic activities, alkaline phosphatase; So me w ere fixed for Transmition Electron Microscope (TEM ) studies. Histopathological studies of experimental groups indicated cong estion of spleens, increase of extramedulla areas, capsule thick ness, capsule fibrosis, number of polymorphonuclear cells, and appearance of subcutaneous hemorraghes. Biochemical studies showed an increase in the level of alkaline phosphatase. TEMs demonstrated damaged, degenerated cells, damaged nuclear membranes and mitochondria, in addition to deformed nuclei and mitochondria, and splenic lesion, in experimental groups. In general, quinazolinones created numerous pathogenic, bioch emical and cellular u ltrastructure disturbances in Balb/C mice embryonic spleens, confirming them as teratogens and toxicogens. Key w ords: Biochemistry, mice embryos, quinazolinones toxicities, spleen development and TEM studies INTROUCTION Teratology and toxicolo gy, study of abnormal prenatal development and congenital malformations induced by exogenous chemical or physical agents, continues to be a burgeoning area of medical research in the quest for the eradication of preve ntable birth defects. Identification of agents with teratogenic potential from the plethora of drugs and chem icals that human beings come into contact with in their everyday environm ent, is crucial, although only some 10% of congenital anomalies are thought to be caused by teratogens representing roughly one in every thousand live births. They compromise the quality of life for millions of individuals worldwide and cost billions of dollars in health care. Knowledge of the most hazardous substances w ould enab le med ical profession als and would be moth ers to minimize foetal ex posu re to them, helping to achieve the laud able goal of abolishing teratogen-induced malfo rmations. Birth defects, induced by ma ternal exposure to exogenous agents, during pregnan cy, are preventable if the agents themselves can be identified and avoided.
Money, in billions, and manhours has been d edicated to animal-based discovery and characterization methods over decades. Reliable extrapolation from animals data to humans is impossible and virtually all known human teratogens have so far been identified in spite of, rather than b ecau se of, an imal based methods. The burden of this goal currently rests heavily upon animal-based testing. In this research, we examined the dogma of animal-oriented teratology and toxicology, considering their negative aspects, cite specific examples with regard to inter-species concordance/discordance and extrapolation to others, and assess alternatives to the use of animals from a scientific standpoints (Capece et al., 2009; De Santis et al., 2004; Estakh r et al., 2009; Ho et al., 2006; Shams and A ounagh, 2007; Sham s et al., 2006; Shams et al., 2009a; Tren t and Brad ley, 2000). Several reports have documented functional and abnormal effects on the offsprings and emb ryos o f rats and mice exsposed to teratogens and drugs such as thalidomide, alcohol, quinazolinones, …. , inducing congenital defects, morphological, skeletal, and histological abnormalities (Finn ell et al., 2002; Nicolopo ulou-Stam ati et al., 2007; Shams et al., 2009b;
Corresponding Author: S.L. Maryam, Developmental Biology, Animal Sciences, Faculty of Biological Sciences, ShahidBeheshti University (SBU), G.C.,Tehran, Iran 1
Current Research Journal of Biological Sciences
Fig. 1: 17-days old Balb/C mice embryos of experimental groups 1 and 2,with subcutaneous hemorraghes on their heads(A-C,white arrows),necks and heads(B,black arrows),heads and backs(D,black arrows),whole body(E,black arrows),heads,necks and lateral regions(F-G,white arrows),and meromelia anomalies(H-J,black arrows)(400x). methylcellulose (the solvent) (Maggio et al., 2001), and control groups were injected with 10ml/kg/ body weight of distilled water. Effects of these two new com ponents of QPPE and Q EPE (Dabiri et al., 2004) on the level of alkaline phospha tase (by spectrophotometer), histological (using different staining m ethod s of H &E , retichulin jones, and trichrome, if there were any precipitation, increase in connective tissues and for making the stromas distiguishable), and intracellular structu res (by transmission electron microscope (Center of Electron Microscopy, M edic a l Sc hool, Shahid-Beheshti University) (Reimer and K ohl, 2008) of spleens of randomly chosen normal and abno rmal 17-days old emb ryos o f Balb /C m ice of all group s, were studied. Data were analyzed by statistical packages for social sciences (SPSS, version 15). Histograms [ P 2 ( 3,N=10 0)=4 3/24,P
