Enterosorption as a method to decrease the systemic toxicity of cisplatin

Abstract

A perspective adsorptive method to minimize systemic toxic effects of chemotherapy is enterosorption (ES). However, the capabilities of this method are far from being completely studied. The question remains opened — should ES be initiated in the first hours on completing cytostatic infusion without the risk of their anticancer activity to be decreased. Aim: to analyze ES influence on anticancer activity and toxic reactions of cisplatin (CP) upon the use of carbon enterosorbent in 1 h after intravenous administration of cytostatic. Methods: CP at the dose of 1 mg/kg body weigh (BW) was administered to Guerin carcinoma-bearing rats each second day for two weeks. Enterosorbents on the basis of highly activated carbon fibers were administered by per os daily 1 h after CP injection. 3 days after the last CP administration the rats were weighted and blood under ether narcosis has been taken for biochemical examination. Tumors and innate organs were isolated, weighted, and fixed in 4% buffered formalin for morphologic examination. Results: In rats administered with CP at the background of ES, BW loss was in 1.6 times lower than in animals after CP session. Relative kidney weight in CP-treated rats was 33.9% higher than in normal ones (p ≤ 0.05). No significant differences were detected between relative kidney weights in the CP + ES-treated and intact animals. Introduction of ES allowed prevent an 30% increase of creatinin content observed in blood plasma after CP treatment (р ≤ 0.05). Urea content was 1.7 times lower in blood plasma of CP + ES-treated rats than after CP treatment. CP caused significant toxic injuries in kidneys, liver, and spleen tissues. Morphologic structure of organs in rats treated with CP at the background of ES was affected at much lower degree. In tumors, large areas of newly formed connective tissue and blood vessels have been fixed after the CP+ES action instead of large necrotic area observed after CP treatment. ES caused insignificant suppression of Guerin carcinoma growth and had additional impact to inhibitory action of CP. Conclusion: Active carbon enterosorbents which are administrated just 1 h after CP administration possesses detoxicating potential sufficient for significant elimination of toxic effect of the cytostatic at the background of complete preservation of its antitumor activity.