ABSTRACT
Gemcitabine is known to exert a therapeutic effect on brain tumors despite the limited permeability of the blood-brain barrier (BBB). In our experimental research single intraperitoneal (i.p.) injection of gemcitabine 25 mg/kg provided increase in median survival of mice with intracranially transplanted Ehrlich carcinoma by 41-89% (p < 0.001). In this experimental model i.p. administration of gemcitabine (permeability of the BBB of less than 10%), carmustine (good permeability of the BBB), cyclophosphamide (poor permeability of the BBB) and cisplatin (doesn't penetrate through the BBB) increased median survival of mice by 88% (p < 0.001), 59% (p = 0.001), 35% (p = 0.005) and 18% (p = 0.302) respectively. Considering strong correlation between antitumor activity of the drugs (carmustine, cyclophosphamide and cisplatin) and their permeability of the BBB, efficacy of gemcitabine in intracranial tumors could be due to its wide range of therapeutic doses.
Subject(s)
Antimetabolites, Antineoplastic/pharmacology , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Blood-Brain Barrier , Brain Neoplasms/drug therapy , Carcinoma, Ehrlich Tumor/drug therapy , Deoxycytidine/analogs & derivatives , Animals , Antimetabolites, Antineoplastic/administration & dosage , Blood-Brain Barrier/drug effects , Blood-Brain Barrier/metabolism , Brain Neoplasms/etiology , Carmustine/administration & dosage , Cisplatin/administration & dosage , Cyclophosphamide/administration & dosage , Deoxycytidine/administration & dosage , Deoxycytidine/pharmacology , Injections, Intraperitoneal , Male , Mice , Neoplasm Transplantation , GemcitabineABSTRACT
An experimental model of solid tumor of Ehrlich failed to reveal any influence of the hepatoprotector Metrop GP on tumor growth or affect antitumor action of doxorubicin.
Subject(s)
Antibiotics, Antineoplastic/pharmacology , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Ehrlich Tumor/drug therapy , Carcinoma, Ehrlich Tumor/metabolism , Chemical and Drug Induced Liver Injury/prevention & control , Doxorubicin/pharmacology , Liver/drug effects , Protective Agents/pharmacology , Animals , Area Under Curve , Chemical and Drug Induced Liver Injury/etiology , Female , Mice , Mice, Inbred Strains , Treatment FailureABSTRACT
Our paper presents the results of preclinical evaluation of the mitigating effect of Metrop GP on the acute toxicity and hepatotoxicity induced by paclitaxel and doxorubicin treatment using functional samples and biochemical and morphological techniques.
