Prevention of Myelosuppression by Combined Treatment With Enterosorbent and Granulocyte Colony-Stimulating Factor

Abstract

Hematotoxicity and its complication are the prominent limiting factors for rational treatment of malignancies. Granulocyte colonystimulating factor (G-CSF) is used to increase granulocyte production. It has been shown previously that enterosorption causes prominent myeloprotective activity also. Still, no trial was performed to combine both of them. Aim: To study the influence of combination of enterosorption and pharmaceutical analogue of naturally occurring G-CSF (filgrastim) on bone marrow protection and the growth of grafted tumor in a case of injection of melphalan (Mel). Materials and Methods: Mel injections were used for promotion of bone marrow suppression in rats. Carbon granulated enterosorbent C2 (IEPOR) was used for providing of enteral sorption detoxifying therapy. Filgrastim was used to increase white blood cells (WBC) count. Results: The simultaneous usage of enterosorption and filgrastim had maximum effectiveness for restoring of all types of blood cells. WBC count was higher by 138.3% compared with the Mel group. The increase of platelets count by 98.5% was also observed. In the group (Mel + C2 + filgrastim) the absolute neutrophils count was twofold higher, in comparison with rats of Mel group. Conclusion: Simultaneous admin istration of G-CSF-analogue and carbonic enterosorbent C2 is a perspective approach for bone marrow protection, when the cytostatic drug melphalan is used. Such combination demonstrates prominent positive impact on restoring of all types of blood cells and had no influence on the antitumor efficacy.

Sorption Detoxification as an Addition to Conventional Therapy of Acute Radiation Sickness and Iatrogenic Leukopenia

“…The important issue is that combination of G-CSF and carbon adsorbents [69] as well as enteral sorption therapy use alone [65] does not affect the efficacy of anticancer treatment; we proved it by our experiments on Guerin tumor-grafted rats.…”

“…Abovementioned positive results led us to design of a new improved version of carbon oral adsorbent, which was used in early experiments [64,68]. An old prototype C1 and his new version C2 were approved on the model of melphalan-induced bone marrow suppression [69][70][71]. We demonstrated that myeloprotective action of carbon granulated enterosorbent С1 (bulk density of 0.28 g/cm 3 , specific surface of 1719 m 2 /g and mesopore area of 239 m 2 /g) is significantly less compared to effects of adsorbent C2 with bulk density of 0.18 g/cm 3 , total specific surface of 2162 m 2 /g and mesopore area of 565 m 2 /g (Figure 14).…”

The effect of two formulations of carbon enterosorbents on oxidative stress indexes and molecular conformation of serum albumin in experimental animals exposed to CCl4

“…chemotherapy [36,37,38,39,40,41,42,43]. All these reports evidenced on significant positive therapeutic pathomorphosis of mentioned pathologies under the influence of enterosorption, first of all, on acceleration of reparative processes in damaged organs and tissues.…”

Melphalan-Induced Cytotoxicity in the Bone Marrow of Rats by Flow Cytometry Measurements

“…Interestingly, as for melphalan, its dose-response relationship resembles that for IR as evidenced by the shape of the survival curve [24]. A series of studies has been initiated towards tackling melphalaninduced BM suppression [26,27], and, in this regard, monitoring of BM recovery by FCM could be helpful as well.…”