Purpose: This study was aimed to
assess the expression of caspase 8 and caspase 9 in the epidermis, during
apoptosis after cladribine administration. Materials and Methods: The
experiment was carried on 10 Wistar rats. The animals were placed into 2 groups:
control group and experimental group. Animals in the control group, in addition
to standard feed and water, were injected with a physiological salt in a
quantity corresponding to the drug dosage, over the course of the experiment.
The experimental group animals were treated with cladribine in the dose of 0.07
mg/kg/24h, for 6 consecutive days in the morning, in 3 cycles with a 5-week gap
in administering the drug. After the completion of the experiment, the animals
were decapitated, and full thickness slices of skin were taken from all the
rats for immunohisto- chemical study. The results of the statistical surveys
were analysed in Statistica 10.0. The difference in intensity of expression of
caspase 9 and caspase 8 in the groups were investigated using the Chiquadrat
test. Statistical significance was considered at p < 0.05. Results: The
statistical analysis found significant correlation in expression of caspase 9
between examined groups (p < 0.0001). There were no statistical relationships
in the presence of the expression of caspase 8 between examined groups (p = 0.0526).
Conclusion: Our findings suggest that mechanism of apoptosis in the rats’
epidermis, induced by cladribine given in the scheme used in the treatment of
MS in humans, involves caspase 9 activity. This means that 2-CdA initiates
the intrinsic apoptosis pathway.
Cite this paper
Chylinska-Wrzos, P. , Wawryk-Gawda, E. , Lis-Sochocka, M. , Jedrych, M. , Lancut, M. , Bulak, K. , Leszcz-Stankiewicz, J. and Jodlowska-Jedrych, B. (2013) The intrinsic or the extrinsic pathways of apoptosis in the epidermis after cladribine application?. Journal of Biomedical Science and Engineering
, 265-272. doi: 10.4236/jbise.2013.63033
 Robak, T., Lech-Maranda, E., Korycka, A. and Robak, E. (2006) Purine nucleoside analogs as immunosuppressive and antineoplastic agents: Mechanism of action and clinical activity. Current Medicinal Chemistry, 13, 3165-3189. doi:10.2174/092986706778742918
 Robak, T., Korycka, A., Lech-Maranda, E. and Robak, P. (2009) Current status of older and new purine nucleoside analogues in the treatment of lymphoproliferative diseases. Molecules, 14, 1183-1226.
 Leist, T.P. and Ver-mersch, P. (2007) The potential role for cladribine in the treat-ment of multiple sclerosis: Clinical experience and development of an oral tablet formulation. Current Medical Research & Opinion, 23, 2667- 2676. doi:10.1185/030079907X233142
 Leist, T.P. and Weissert, R. (2011) Cladribine: Mode of action and implications for treatment of multiple sclerosis. Clinical Neuropharmacology, 34, 28-35.
 Spurgeon, S., Yu, M., Phillips, J.D. and Epner, E.M. (2009) Cladribine: Not just another purine analogue? Expert Opinion on Investigational Drugs, 18, 1169-1181.
 Saven, A. and Piro, L.D. (1994) 2-Chlorodeoxyadenosine: A newer purine analog active in the treatment of indolent lymphoid malignancies. Annals of Internal Medicine, 120, 784-791.
 Hartung, H.-P., Aktas,O., Kieseier, B. and Comi, G. (2010) Development of oral cladribine for the treatment of multiple sclerosis. Journal of Neurology, 257, 163-170.
 Maciejek, Z. (2005) Diagnostyka stwardnienia rozsianego. Farmakoterapia w Psy-chiatrii i Neurologii, 3, 209-217.
 Gasperini, C., Ruggieri, S. and Pozzilli, C. (2010) Emerg- ing oral treatments in multiple sclerosis-clinical utility of cladribine tablets. Therapeutics and Clinical Risk Management, 6, 391-399.
 Kasper, L.H. and Shoemaker, J. (2010) Multiple sclerosis immunology. The healthy immune system vs the MS immune system. Neurology, 74, S2-S8.
 Losy, J. (2004) Patogeneza oraz aktualne kryteria diag- nostyczne stwardnienia rozsianego. Neurologia i Psychi- atria, 4, 53-56.
 Crews, K.R., Wimmer, P.S., Hudson, J.Q., Howard, S.C., Ribeiro, R.C. and Razzouk, B.I. (2002) Pharmacokinetics of 2-chlorodeoxyadenosine in a child undergoing hemo- filtration and hemodialysis for acute renal failure. Journal of Pediatric Hematology/Oncology, 24, 677-680.
 Ewald, B., Sampath, D. and Plunkett, W. (2008) Nucleo- side analogs: Molecular mechanisms signaling cell death. Oncogene, 27, 6522-6537. doi:10.1038/onc.2008.316
 Johnston, J.B. (2011) Mechanism of action of pentostatin and cladribine in hairy cell leukemia. Leuk Lymphoma, 52, 43-45. doi:10.3109/10428194.2011.570394
 Stańczyk, M. and Majsterek, I. (2008) Apoptoza-cel ukie-runkowanej terapii przeciwnowotworowej. Post?py Biologii Komórki, 35, 467-484.
 St?pień, A., Izdebska, M. and Grzanka, A. (2007) Rod- zaje ?mierci komórki. Post?py Higieny i Medycyny Do- ?wiadczalnej, 61, 420-428.