Effects of quinazolinones on the development of Balb/C mice embryonic kidneys

ABSTRACT

Quinazolinones are heterocyclic components [able to form cyclized compounds] which have several medical effects such as anti-malarial, spasmolytic, anti-microbial, sedative, etc. They are also known for their fungicidal properties, inhibition of tyrosine-kinase and DNA repair enzyme poly [ADP-ribose] polymerase [PARP] and are also effective in treatment of cancer, diabetes, and parkinsonism complications. In this study, for the first time different aspects of developmental effects of two new Quinazolinone components [QPPE and QEPE], on kidneys of Balb/C mice embryos were investigated. Pregnant Balb/C mice were divided into four groups of control [n=30], sham [n=30], experimental 1 [n=30] and experimental 2 [n=30]. Control mice remained intact, sham and two experimental groups received 0.05% methyl cellulose and 100 mg/kg/body weight [most effective dose] of QPPE and QEPE, intraperitoneally [IP], on day 10th of gestation. Kidneys were removed by c-sections, stained with H and E, PAS, trichrome, reticholin and jones staining. Some embryonic kidneys were prepared for measurements of level of alkaline phosphatase and TEM studies. Light and TEM microscopes, and level of enzyme surveys demonstrated that QPPE and QEPE are toxic components, creating protrusions at the surface of convoluted proximal tubules, protein casts, renal necrotic cells, pseudothyroidezation, mitochondria degeneration, hyperemia, glomeruli hypertrophy, widening of renal spaces, vacuolization, as well as decrease in the number of brush border villi and level of alkaline phosphatase. By being teratogens and toxins, these two new derivatives affected development of embryonic kidneys at histological, biochemical and intracellular levels; QEPE had more effects and convoluted proximal tubules were more sensitive than convoluted distal tubules