The Effect of Rapamycin on the Cyclin D Expression in Some Tissues of Swiss Albino Mice Mus Masculus Embryos

Main Article Content

Sada Ghalib Taher
Muntadher Lutfi Taher
Riyadh Rashid Hameed
Ali Naeem Salman
Nahla A. Al-Bakri

Abstract

The current study aimed to investigate the effects of Rapamycin (Rapa) on the cyclin D expression in heart and liver tissues of Swiss albino mice Mus masculus embryos at different Embryonic Developmental stages. The study conducted on Thirty- two pregnant albino mice, were randomly divided into four groups, each group contained eight pregnant mice. Each group received Rapamycin (Rapa) at different doses, via intraperitoneally injection (IP), at different gestational days until the conclusion of the designated times, whereas the control groups received a DMSO. Pregnant mice were administered the desired doses under the same environmental circumstances. According to pharmacological constitutions, body weight was used to establish the dosages. After that, on days 13th and 16th, the mice were put to killing. Current study used another two concentrations from drug, one less than the therapeutic dosage (0.75mg/kg of Rapamycin) and another more than the therapeutic dosage (3mg /kg of Rapamycin). Quantification of the IHC of cytoplasmic proportion and intensity showed cytoplasmic expression of Cyclin D in tissue of mice embryos heart the control group and other treatment groups differed significantly from one another at (P <0.05), while there wasn't a significant difference between the treatment groups which received 0.75 and 1.5mg/kg of Rapamycin, in embryonic liver tissue. At gestation day 16th, there was no significant difference in expression of Cyclin D between control group and treated group with 0.75mg/kg of Rapamycin, while there was a significant difference in Cyclin D expression at (P < 0.05) between treated groups with 0.75mg/kg of and treated group with 1.5 and 3 mg/kg of Rapamycin and from these results we concluded that the use of Rapamycin has been affected on checkpoints of cell cycle during embryogenesis, which appeared through its effects on cyclin D expression.

Article Details

How to Cite
Sada Ghalib Taher, Muntadher Lutfi Taher, Riyadh Rashid Hameed, Ali Naeem Salman, & Nahla A. Al-Bakri. (2024). The Effect of Rapamycin on the Cyclin D Expression in Some Tissues of Swiss Albino Mice Mus Masculus Embryos. International Journal of Pharmaceutical and Bio Medical Science, 4(3), 244–252. https://doi.org/10.47191/ijpbms/v4-i3-19
Section
Articles

References

I. Abdurrauf, Y.; Ahmet, A.; Atessahin, O.; Ali, C. and Mesut, A. (2007). Ellagic acid prevent Cisplatin 10 mg kg-1 platin-Induced oxidative stress in liver and heart tissue of rats. Basic. Clin. Pharmacol. Toxicol. (101).Pp:345-349.

II. Ahmed ,Aya Ali Abbas .(2019). Toxicity of Bile Salts in Mice: Liver-Kidney Axis Thesis. Forensic Medicine and Toxicology Department Faculty of Veterinary Medicine South Valley University Qena, Egypt.

III. AL_Musawi ,Sada .,Gh and Ali, Naeem Salman (2018) : Study the Effect of Dexamethasone on the External morphology features at different Embryonic Developmental stages in the Swiss Albino Mice Embryos. Journal of Thi-Qar University Vol.13 No.1 126-138.

IV. Al-Easawi, Nada Abdulrahman F; Al-Azzawi, Muhammad Nafea Ali (2016). Histological study in liver of albino mice post exposing to shisha smoke.3(1):30-35.

V. Bancroft, J.D.and Gamble, M. (2008). Theory and practices of histological technique.2nd ed. Churchill Elseivier .London.,p: 56.

VI. Baratta, Janie L Ngo; Anthony Lopez; Bryan Kasabwalla; Natasha Kenneth J and Robertson , Richard T(2009). Cellular Organization of Normal Mouse Liver: A Histological, Quantitative Immunocytochemical, and Fine Structural Analysis Janie ,Histochem Cell Biol. 131(6). 713–726.

VII. Bernard PS, Keith LP.( 2011).Goodman& Gilman’s the pharmacological basis of therapeutics. 12th ed. New York: McGraw Hill companies.

VIII. Bin Rubaia’an, M. A., Alotaibi, M. K., Alotaibi, N. M., & Alqhtani, N. R. (2021). Cortisol in oral and maxillofacial surgery: a double-edged sword. International Journal of Dentistry, 2021.‏

IX. Bogumil, B., Wlodarczyk, B., & Minta, M. (2000). Effect of sodium valproate on rat embryo development in vitro. Bullent Veterinary Institute in Pulway, 44(2), 202–206.

X. Boorman, G. A., Eustis, S. L., Elwell, M. R., Montgomery, C. A. J., and MacKenzie, W. F. (1990). Pathology of the Fischer Rat: Reference and Atlas. Academic Press, San Diego, CA.

XI. Cardell RR. (1974). Action of metabolic hormones on the fine structure of rat liver cells. III Effects of adrenalectomy and administration of cortisone. Anat Record. 180(2): 309-30.

XII. Cuyas, Elisabet., Corominas-Faja, Brun., Joven, Jorge., Menendez, Javier.A., (2014). Cell cycle regulation by the nutrient-sensing mammalian target of rapamycin(mTOR) pathway.Methods Mol. Biol. 1170, 113e144.

XIII. D. Purves, J.W. Lichtman,( 1985 ). Principles of Neural Development, Sinauer Assocs,Sunderlande,

XIV. Damayanti, I. A. M., Indrayoni, P., Antari, N. W. S., & Padmiswari, A. A. I. M.(2021). Effectiveness of Averrhoa bilimbi leaf extract on spermatogenic cells ofmice (Mus Musculus L.) hyperglycemia. International Journal of Health &Medical Sciences, 4(2), 273-279. https://doi.org/10.21744/ijhms.v4n2.1747

XV. Galliani I, Santi P, Falcieri E. (1993)Morphological aspects of steroid hormone action on rat hepatocyte. Boll Soc Biol Sper.; LXIX (3): 145-51.

XVI. Garfield AS, Mohamed SA, Cardell RR.(1984).The effects of insulin replacement and withdrawal on hepatic ultrastructure and biochemistry. Am J Anat. 170: 127-42.

XVII. Garfield SA, Scott AC, Cardell RR. (1978). Alterations in hepatic fine structure after chronic exposure of rats to dexamethasone. Anat Rec 192(1): 73-87.

XVIII. Giorgio A, Valerio Mattia S, Laura T, Marina C, Gloria A, Marco B. (2010)Pathophysiology of dyslipidemia in Cushing’s syndrome. Neuroendocrinology. 92 (1):86-90.

XIX. Hashemolhosseini, Said., Nagamine, Yoshikuni., Morley, Simon., Desrivières, Sylvane., Mercep, Luka., and Ferrari, Stefano. (1998). Rapamycin inhibition of the G1 to S transition is mediated by effects on cyclin D1 mRNA and protein stability. Journal of Biological Chemistry, 273(23), 14424-14429.‏

XX. Hunter, M.P., Wilson, C.M., Jiang, X., Cong, R., Vasavada, H., Kaestner, K.H., and Bogue, C.W. (2007). The homeobox gene Hhex is essential for proper hepatoblast differentiation and bile duct morphogenesis. Dev. Biol. 308, 355–367.

XXI. Kiernan, F. (1833). The anatomy and physiology of the liver. Philosophical transactions of the Royal Society of London, 123, 711-770.‏

XXII. Kim, M. and Shin, H.K. (1998). The water-soluble extract of chicory influences serum and liver lipid concentrations, cecal short-chain fatty acid concentrations and fecal lipid excretion in rats. J. Nutr., 128: 1731-

XXIII. Lee KH, Chen YS, Judson JP, Chakravarthi S, Sim YM, Er HM .(2008), The effect of water extracts of Euphorbia hirta on cartilage degeneration in arthritic rats. Malays J Pathol 30:95-102.

XXIV. Mescher AL.(2010) Liver. In: Junqueira’s Basic Histology, 12th ed. McGraw Hill Company; 287-96.

XXV. Nelsen, Christopher. J., Rickheim, David. G., Tucker, Melissa.M., Hansen, Linda. K., and Albrecht, Jeffrey.H.(2003).Evidence that cyclin D1 mediates both growth and proliferation downstream of TOR in hepatocytes. Journal of Biological Chemistry, 278(6), 3656-3663.‏

XXVI. Rappaport, A. M., Borowy, Z. J., Lougheed, W. M., & Lotto, W. N. (1954). Subdivision of hexagonal liver lobules into a structural and functional unit. Role in hepatic physiology and pathology. The anatomical record, 119(1), 11-33.‏

XXVII. Roger WA,Rueoner BH.(1977). Aretospective study of probable glucocorticoid-induced hepatopathy in dogs .JAVMA;170(6):603-606.

XXVIII. Saadalla, R. (2009). Pathological effects of ethambutol on some parts of the central nervous system of mouse embryos. Iraqi Journal of Veterinary Sciences, 23(2), 393–402.

XXIX. Sapolsky RM, Romero LM, Munck AU. (2000). How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory and preparative actions. Endocr Rev. 21: 55-89.

XXX. Sethunath ,Deepak.(2018). Detection of histological features in liver biopsy images to help identify non-alcoholic fatty liver disease , master thesis .Department of Computer and Information Sciences Indianapolis, Indiana

XXXI. Shi, K., Jiang, J., Ma, T., Xie, J., Duan, L., Chen, R., Zheng, J. (2014). “Dexamethasone attenuates bleomycin-induced lung fibrosis in mice through TGF-β, Smad3 and JAK-STAT pathway”. International Journal of Clinical and Experimental Medicine, 7 (9), 2645–2650.

XXXII. Striffler JS, Cardell EL, Cardell RR.( 1981).Effects of glucagon on hepatic glycogen and smooth endoplasmic reticulum. Am J Anat. 160: 363-79.

XXXIII. Taher, Sada Ghalib(2022) . Protein expression of cyclin D and E of Embryonic developmental stages in mice embryos Mus masculus under the influence of treatment with different concentrations of Rapamycin by use immunohistochemistry technique, A Doctoral Dissertation, University of Thi-Qar, College of Education for Pure Sciences , department of Biology .

XXXIV. Tayfur,S.(2013).Morphological and Histopathological effect of Dexamethasoe on the Embryo of white Mus musculus mice. Diyala journal for pure sciences;10(3):80–90

XXXV. Wang, S. H., Li, L. H., Zou, D. M., Zheng, X. M., & Deng, J. (2020). Roles of the mammalian target of rapamycin (mTOR) signaling pathway in the repair of hyperoxia-induced acute lung injury. Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University, 29(1), 13-23.‏

XXXVI. Foster, David., Yellen, Paige., Xu, Limei., Saqcena, Mahesh.(2010). Regulation of G1 cell cycle progression: distinguishing the restriction point from a nutrient-sensing cell growth checkpoint(s). Genes Cancer 1, 1124e1131.

XXXVII. Oka,Kiyomasa.,OhyaShimada,Wakana., Shinya ,Mizuno., Nakamuraa, Toshikazu.(2013).Up-regulation of cyclin-E1 via proline-mTOR pathway is responsible for HGF-mediated G1/S progression in the primary culture of rat hepatocytes. Biochemical and biophysical research communications, 435(1), 120-125.‏

XXXVIII. Medema, René. H., Kops, Geert. J., Bos, Johannes. L., and Burgering, Boudewijn. M. (2000). AFX-like Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27 kip1. Nature, 404(6779), 782-787.‏

XXXIX. Law, Mary.,Forrester, Elizabeth., Chytil, Anna., Corsino, Patrick., Green, Gail.,Davis, Bradley., Thomas Rowe,1 and Brian Law(2006). Rapamycin disrupts cyclin/cyclin-dependent kinase/p21/proliferating cell nuclear antigen complexes and cyclin D1 reverses rapamycin action by stabilizing these complexes. Cancer research, 66(2),1070-1080.‏

XL. Espeillac, Catherine., Mitchell, Claudia., Celton-Morizur, Séverine., Chauvin, Celton., Koka, Vonda., Gillet, Cynthia., Albrecht, Jeffrey ., Desdouets, Chantal and Pende, Mario. (2011). S6 kinase 1 is required for rapamycin-sensitive liver proliferation after mouse hepatectomy. The Journal of clinical investigation, 121(7), 2821-2832.‏