Study on the Reduction of Chemotherapy Induced Neutropenia in Mice Using Glucosaminylmuramyl Dipeptide

Abstract

Neutropenia is a common and often dose limiting side effect of some chemotherapy regimens. The aim of this study was to investigate the ability of an immunomodulator, glycosaminylmuramyl dipeptide (GMDP, CAS 78113-36-7, romurtide) to reduce chemotherapy induced neutropenia. BALB/c mice were treated with 200 mg kg-1 cyclophosphamide (CY) to induce a reversible neutropenia lasting approximately 6-7 days. There was no change in the duration or depth of neutropenia in mice treated with GMDP for 3 consecutive days (2.5 or 25 mg kg-1) starting the day after CY injection. In addition, at the doses used, the time of administration of GMDP relative to CY did not alter this response. However, a marked neutrophilia compared to controls was consistently observed in all cases. Neutrophil counts of up to 14 times the baseline value were measured 6-7 days after the induction of neutropenia. GMDP had no effect in the absence of CY. Less variation was seen in white cell counts of older non-SPF mice treated with CY. When the activity of GMDP (5 mg kg-1) was compared with G-CSF (granulocyte colony stimulating factor, 100 micrograms kg-1) in these animals, GMDP showed a consistent trend to reduce the length of neutropenia, however, under the conditions tested only G-CSF treatment resulted in a significant reduction in the duration of neutropenia. In the 12-week-old mice, the neutrophilia seen with both G-CSF and GMDP was much smaller than in the 8-week-old mice, and was not significantly different from that in control mice treated with CY alone.

Strategies for Using Muramyl Peptides - Modulators of Innate Immunity of Bacterial Origin - in Medicine

“…The introduction of the drug licopid into medical practice was preceded by numerous preclinical and clinical studies in Australia (112), Great Britain (113)(114)(115) and Russia (116,117), during which a wide spectrum of biological activity of glucosaminylmuramyldipeptide was revealed. GMDP stimulates development of both cellular and humoral immune responses.…”

“…Clinical trials of the drug licopid took place in Australia (UNSW Department of Surgery and Department of Oncology, The St. George Hospital), Great Britain (Toxicol Laboratories Ltd, The Royal Masonic Hospital) and in the leading medical institutions in Russia and the CIS countries in accordance with international rules of proper clinical practice (Good Clinical Practice, GCP) using randomized double control (112)(113)(114)(115)(116)(117). The drug licopid is widely used in Russia and CIS countries, every person can buy it without prescription (in dose 1 mg per tablets).…”