Autophagy in the pancreatic islets after the administration of cladribine in accordance to two different modes of therapy

The treatment of neoplastic and neurodegenerative diseases is still difficult. This because the cytostatic drugs have adverse effects on healthy organs. Among the drugs that have been investigated in the therapy of cancers and multiple sclerosis are the purine analogues. The aim of our study was the evaluation of the effect of cladribine on the process of autophagy in the healthy pancreas via two dosage models. The experiment was conducted on female Wistar rats which were placed within the experimental and control groups of two dosage models: model (A) - cladribine being administered in a daily dose of 0.1 mg/kg by weight for 7 days, and model (B) - cladribine being administered in a daily dose of 0.07 mg/kg by weight in 3 cycles of 6 days with 5 weeks break. A-bis and B-bis groups were included within, respectively, groups A and B. Here, decapitation occurred after 4 weeks break in drug administration. In our work, autophagy was investigated via the expression of the LC3B protein (Light Chain 3B protein). The comparison of the results of many independent trials was built upon the use of the Kruskal-Wallis non-parametric test. Significance was set at p < 0.005. In our results, average LC3B expression was observed in 100% of all cells in the group A, 70% in group B and 60% in group B-bis. We not observed average LC3B expression in the other groups. Moreover, a poor reaction was observed in 55% of all cells in group A-bis. We noted significant relationships between control group and group A, between the control group and group B, and between group A-bis and groups B and B-bis. These results demonstrate that cladribine has led to the induction of autophagy in the pancreatic islet cells

A comparison of caspase 3 expression in the endocrine and exocrine parts of the pancreas after cladribine application according to the "leukemic" schema

The therapeutic effects of the immunosuppressive agent, cladribine, have been demonstrated by its toxicity to cells. However, its effects on healthy cells of the body is poorly understood. The aim of study was, hence, to, firstly, evaluate the morphology of the endocrine and exocrine pancreas after the administration of cladribine according to the "leukemic" schema, and, secondly, to assess its impact on the intensity of apoptosis. The experiment was carried out on female Wistar rats which were placed within the control group KA, and the experimental groups: A and A-bis. In the experimental groups, Cladribine was administered according to the cycle used to treat human hairy cell leukemia. In group A, the material was taken 24 hours after administration of the last dose of the drug, while in group A-bis, this was done after a 4 weeks break. The reaction was assessed to be average in 80% of all cells in group A, and in 64% of all acinar cells in group KA, while in group A-bis, the majority of the exocrine cells demonstrated a lack of immunohistochemical response (72%). Moreover, most endocrine cells (60%) in group A-bis revealed a strong reaction, while in Group A, the corresponding figure is a little over 34%. A comparison of the severity of the caspase 3 expression in both the exocrine and endocrine pancreas showed significant differentiation results between the group KA and group A-bis, and between group A and A-bis (p < 0.0001). In can be concluded that endocrine cells are more sensitive to cladribine than are exocrine cells