Role of fibronectin under conditions of doxorubicin action

Abstract

There is no standard as to treatment of anthracycline chemotherapy complications. The reduction of cytotoxic drugs toxicity without weakening of their antitumor action remains relevant. The extracellular matrix which key component is fibronectin is present in all tissues and it continuously undergoes controlled remodeling. So, the purpose of our work was to study the level of fibronectin in the experimental model of doxorubicin-induced cardiomyopathy and effects of this cytostatic and its co-administration with antioxidants of different nature.The level of fibronectin was measured by ELISA using monospecific antibodies against fibronectin (Sigma, USA), secondary anti-IgG labeled with horseradish peroxidase (Sigma, USA) and fibronectin standard (Sigma, USA). The study was conducted on Wistar male rats with weight of 210 ± 50 g which were divided into 4 groups by 8 animals in each group: 1 – control, rats receiving saline i/p; 2 – doxorubicin 1 mg/kg i/p once a week during 4 weeks; 3 – doxorubicin by the same scheme plus 1% 2-oxoglutarate in drinking water during 4 weeks;4 – doxorubicin by the same scheme and korvitin injection 30 min before doxorubicin application once a week during 4 weeks. Obtained data indicate the effect of doxorubicin to decrease in index mass heart in 38% of animals compared to control animals; decrease in total protein concentration by 8% (Р < 0,05) and increase of the level of fibronectin by 67% (P < 0,001) in blood plasma of rats and decrease in the level of fibronectin in the heart extract by 19% (Р < 0,05) under development of doxorubicin-induced cardiotoxicity. Increased fibronectin concentration in blood plasma had strong correlation with decreased total protein concentration in blood (r=0,80) and heart extract (r=0,59) in rats with doxorubicin-induced cardiomiophaty indicating the sensitive reaction of fibronectin to development of metabolic disorders under doxorubicin influence.