Journal Article Epublish
PubMed: 40806214 DOI: 10.3390/ijms26157081
Efficacy of Poloxamer 188 in Experimental Myelosuppression Model Induced by Carboplatin in CBA Mice.
Int J Mol Sci 26(15)
Authors: Arina V Kholina, Natalya A Borozdina, Victor A Palikov, Evgeniy S Mikhaylov, Irina N Kravchenko, Renata A Dalevich, Irina A Pakhomova, Ekaterina N Kazakova, Maria A Timchenko, Alexander Ye Yegorov, Maxim V Molchanov, Artem M Ermakov, Olga Y Antonova, Olga Y Kochetkova, Natalia M Pankratova, Anton N Pankratov, Elena V Arshintseva, Sergey Y Pushkin, Igor A Dyachenko, Arkadiy N Murashev
Affiliations
- Branch of the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Pushchino 142290, Russia.
- Institute of Theoretical and Experimental Biophysics (RAS), Pushchino 142290, Russia.
- Institute of Mathematical Problems of Biology (RAS)-The Branch of Keldysh Institute of Applied Mathematics of Russian Academy of Sciences, Pushchino 142290, Russia.
- Medical Emulsions LLC, Pushchino 142290, Russia.
Abstract
Poloxamer 188 is a polymer that is used as a carrier and stabilizer of pharmacological agents. It has been demonstrated to enhance red blood cell and hemoglobin levels in healthy animals and in select clinical cases. The objective of this study was to assess the efficacy of Poloxamer 188 in CBA mice when administered repeatedly in the carboplatin-induced myelosuppression model. The mice were administered carboplatin once at a dose of 100 mg/kg, and then Poloxamer 188 was orally administered daily at doses of 10 mg/kg, 100 mg/kg, 500 mg/kg, and 1000 mg/kg for 7 and 21 days. Poloxamer 188 at a dose of 1000 mg/kg was found to bring the level of 2,3-bisphosphoglycerate in red blood cells close to control level (p = 0.1331 for the control group compared to Poloxamer at a dose 1000 mg/kg) already from day 8 of the study and in bone marrow resulted in regulation of genes responsible for hematopoiesis. G-GSF at day 8 and TNFα at day 22 gene expression was significantly decreased by 54% (p = 0.012) and 16% (p = 0.024), respectively, with Poloxamer 188 administration at a dose of 100 mg/kg. Additionally, in the bone marrow, the treatment was seen to exert a positive regulatory effect on the genes responsible for hematopoiesis. These findings are consistent with the observed increase in red blood cell by 6.7% (p = 0.001), hemoglobin by 4.7% (p = 0.0053), and reticulocyte percentage by 53.6% (p < 0.0001) following Poloxamer 188 administration at a dose of 1000 mg/kg in CBA mice with myelosuppression.
MeSH
Cells, Genes, Hemoglobins, Hematopoiesis, Bone Marrow, Erythrocytes, Blood, Poloxamer, Blood Cells, Carboplatin