BIOCHEMICAL INDICATORS OF HEPATOTOXICITY IN BLOOD SERUM OF RATS UNDER THE EFFECT OF NOVEL 4-THIAZOLIDINONE DERIVATIVES AND DOXORUBICIN AND THEIR COMPLEXES WITH POLYETHYLENEGLYCOL-CONTAINING NANOSCALE POLYMERIC CARRIER

• Published in: Ukrainian biochemical journal 2015-03, Vol.87 (2), p.122-132
• Main Authors: Kobylinska, L I, Havrylyuk, D Ya, Ryabtseva, A O, Mitina, N E, Zaichenko, O S, Lesyk, R B, Zimenkovsky, B S, Stoika, R S
• Format: Article
• Language: English
• Subjects: 4-thiazolidinone derivatives; Alanine Transaminase - blood; Alkaline Phosphatase - blood; alpha-Amylases - blood; Animals; Animals, Outbred Strains; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - toxicity; Blood Proteins - metabolism; blood serum; Creatinine - blood; doxorubicin; Doxorubicin - chemistry; Doxorubicin - toxicity; Drug Carriers; enzyme activity; gamma-Glutamyltransferase; hepatotoxicity; L-Lactate Dehydrogenase - blood; Liver - drug effects; Liver - enzymology; Nanoparticles - administration & dosage; Nanoparticles - toxicity; Polyethylene Glycols - chemistry; polymeric nanocarrier; Rats; Thiazolidinediones - chemical synthesis; Thiazolidinediones - toxicity; Urea - blood
• ISSN: 2409-4943; 2413-5003
• DOI: 10.15407/ubj87.02.122

The aim of this study was to compare the effect of new synthetic 4-tiazolidinone derivatives (compounds 3882, 3288 and 3833) and doxorubicin (positive control) in free form and in their complexes with synthetic polyethyleneglycol-containing nanoscale polymeric carrier on the biochemical indicators of hepatotoxicity in blood serum of rats. The activity of enzymes considered as the markers of hepatotoxicity, as well as. the concentration of total protein, urea and creatinine were measured in blood serum of rats. It was found that after injection of investigated compounds the activities ofalanine aminotransferase, alkaline phosphatase and α-amylase increased in comparison to control. Doxorubicin injection was accompanied by 4-fold increase in the activity of γ-glutamyltransferase, and injection ofcompound 3833 led to 2.5-fold elevation ofthe activity of this enzyme. Complexation ofthese antineoplastic derivatives with a synthetic nanocarrier lowered the activity ofthe investigated enzymes substantially if compared to the effect of these compounds infreeform. The most evident decrease was measured for α-amylase, γ-glutamyltransferase and lactate dehydrogenase activities. The normalization of concentrations of total protein, urea and creatinine in blood serum of rats treated with complexes of the studied compounds with a polymeric carrier comparing with their introduction infreeform was also detected. Thus, the immobilization by novel polymeric carrier of anticancer drugs possessing high general toxicity in the treated organism mitigates their toxic effect, which is evident as normalization of specific biochemical indicators of the hepatodestructive effects of the anticancer drugs.