Qualitative and Quantitative Analysis of the Effects of Quinazolinones on Internal Organs of Newborn Balb/C Mice

Document Type: Original Article

Authors

Developmental Biology,Animal Sciences, Faculty of Biological Sciences, Shahid-Beheshti University (SBU),G.C., Tehran, Iran

Abstract

Objective(s)
Quinazolinones are heterocyclic compounds, with biological and pharmacological activities, such as inhibiting some proteins, enzymes and reducing blood lipids.
Materials and Methods
Following previous results of our group, effects of two new derivatives of quinazolinones 9(3)-quinazolinone-2-propyl-2-phenylethyl (QPPE) and 9(3)-quinazolinone-2-ethyl-2-phenylethyl (QEPE) on livers, intestines and kidneys of newborn Balb/C mice were investigated. Pregnant mice were divided into four groups of control, sham, experimental 1, treated with QPPE, and experimental 2, treated with QEPE. Experimental groups received 100 mg/kg body weight (most effective dose) of QPPE and QEPE, sham groups received methyl cellulose 0.05% (the solvent) and control groups received distilled water, intraperitoneally (IP), on day 8 of gestation. Five days after birth, livers, intestines and kidneys were removed, fixed in formalin 10%, stained with hematoxylene and eosin for histological and pathological studies.
Results
Results showed appearance of fatty changes in livers, an increase in diameters of hepatocytes and central veins of livers, and reduction in the lengths of villi of proximal, middle and distal segments of newborn Balb/C mice intestines. Furthermore, there was a diminished diameter of the lumen of the proximal tubules, and average diameter of the lumen of distal tubules which led to an increase in the number of glomeruli cells of newborn Balb/C mice kidneys.
Conclusion
Regarding inflammation in different parts of the kidneys, livers and intestines, our investigations suggest that quinazolinones may have some toxic effects on embryos.

Keywords


1.Fawzia MR, Amr YE, Soad M, Aida MI, Mona AM. The antihyperlipidemic activities of 4(3H) quinazolinone and two halogenated derivatives in rats. Lipids Health Dis 2005; 4:22-30.

2.Vuong NT, Xing-Ping L, Chun-Lin C, Fatih MU. Treatment of atherosclerosis in apolipoprotein E-deficient mice with 4-(3'-bromobenzoyl)-6,7-dimethoxyquinazoline (WHI-P164), a potent inhibitor of triglyceride synthesis. J Cardiovasc Pharmacol 2000; 35:179-181.

3.Shams Lahijani M, Aounegh R. Teratogenic effects of quinazolinones on balb/C mice fetuses. J Med Sci Res 2007; 1:25-30.

4.Shams Lahijani M, Ahmanzadeh F, Dabiri M. Teratogenic effects of a new derivative of quinazolinone on the development of Balb/C mice embryos on day 9, 10 and 11 of gestation. Iran J Sci Technol Transac A 2006; 30:27-34.

5.Etemad S, Shams Lahijani M. Quinazolinones and nerphrotoxicity in new born Balb/C mice.7th World Congress of Nephrology (WCN); Rio De Janeiro, Brazil, 2007.

6.Rajabi H, Shams Lahijani M. Histological study of liver of newborn Balb/C mice treated with quinazolinones. 11th International Congress of Toxicology (ICT), Montreal, Canada, 2007.

7.Etemad S, Shams Lahijani M. Studying quinazolinones derivatives treatments as kidney cells stress in Balb/C new born mice. World Congress of Stress (WCS), Budapest, Hungary, 2007. 

8.Fadavi M, Shams Lahijani M. Pathological effects of quinazolinones on the small intestine of new bom Balb/C mouse. 11th International Congress of Toxicology (ICT), Montreal, Canada, 2007.

9.Etemad S, Shams Lahijani M. Pathological effects of quinazolinones on Balb/C mice kidneys. 11th International Congress of Toxicology (ICT), Montreal, Canada, 2007.

10.Dabiri M, Salehi P, Khajavi MS, Mohammadi A. Microwae-assisted one-pot three component synthesis of some new 4(3H)- quinazolinone derivatives. Heterocycles 2004; 36: 1417-1421.

11.Placidi GF, Fornaro P, Guarneri M. Autoradiographic distribution study of 14C-2-phenyl-6-sulfonamido-7- chloro-1, 2, 3, 4-tetrahydro-4-quinazolinone (fenquizone) inmice. Arzneimittelforschung 1979; 29:1005-1008.

12.Maggio B, Daidone G, Raffa D, Plescia S, Mantione L, Cutuli VMC, et al. Synthesis and pharmacological study of ethyl 1-methyl- 5- (subsititude 3,4- dihyro- 4- oxoquinaolin 3- yl) -1H- Pyrazole- 4- acetates. Eur J Med Chem 2001; 36:734-742.

13.Condino AA, Barleycorn AA, Lu W, Maheshwari A, Christensen RD, Calhoun DA. Abnormal intestinal histology in neonates with congenital anomalies of gasterointestinal tract. Neonatology 2004; 85:145-150.

14.Morgan MY, Reshef R, Shah RR, Oates NS, Smith RL, Sherlock S. Impaired oxidation of debrisoquine in patients with perhexiline liver injury. Gut 1998; 25:1057-1064.

15.Pessayre D. Role of reactive metabolites in drug-induced hepatitis. J Hepatol 1995; 23: 16-24.

16.Arici M, Chana R, Lewington A, Brown J, Brunskill NJ. Stimulation of proximal tubular cell apoptosis by albumin-bound fatty acids mediated by peroxisome proliferators. J Am Soc Nephrol 2003; 14:17-27.

17.Tzen CY, Tsai JD,Wu TY,Chen BF, Chen ML, Lin SP, Chen SP. Tubulointerstitial nephritis associated with a novel mit ochondrial point mutation. Kidney Int 2001; 59:846-854.

18.Recknagel RO, Glende EA Jr. Carbon tetrachloride hepatotoxicity: an example of lethal cleavage. CRC Crit Rev Toxicol 1973; 2:263-267.

19.Raffa D, Elder MC, Daidone G, Maggio B, Merickech M, Plescia D, et al. Synthesis, cytotoxicity and inhibitory effect on tubulin polymerization of a new 3-heterocyclo substituted 2-styryl quinazolinones. Eur J Med Chem 2004; 39:299-304.

20.Fledman M, Friedman LS, Sleisenger MH. Anatomy/histology/embryology/and developmental anomalies of the small and large intestine. Gasterointestinal and Liver Disease 7thed Philadelphia Pennsylvania 2002; 45:1643-1654.

21.Woolf AS, Hillman KA. Unilateral renal agenesis and the congenital solitary functioning kidney:developmental, genetic and clinical perspectives. BJU Int 2007; 99:17-21.

22.Moritz KM, Dodie M, Wintour M. Kidney development and the fetal programming of adult disease. Bioessays 2003; 2593:212-220.

23.Shimizu A, Masuda Y, Kitamura H, Ishizaki M, Sugisaki Y,Yamanaka N. Apoptosis in progressive crescentic glomerulonephritis. Lab Invest 1996; 74:941-951.

24.Jenette JC, Thomas DB. Crescentic glomerulonephritis.Nephrology Dial Transplant 2001; 16:80-82.

25.Dixon JL, Ginsberg HN. Hepatic synthesis of lipoproteins and apolipoproteins. Semin Liver Dis 1992; 12:364-372.

26.Muriel P, Mourelle M. Prevention by silymarin of membrane alterations in acute CCl4 liver damage. J Appl Toxicol 1990; 10:275-279.

27.Masayasu I, Sato EF, Nishikawa M, Park AM, Kira Y, Imada I, et al. Mitochondrial generation of reactive oxygen species and its role in aerobic life. Cur Med Chem 2003; 10: 2495-2505.

28.Horikoshi S, Tomino Y. Tubulointerstitial nephropathy in mitochondrial cytopathy. Nippon Rinsho 2002; 60:567-570.