Biomedical Research

The objective of this study was to evaluate the role of tonicity-responsive Enhancer Binding Protein (TonEBP) modulation on biochemical parameters in a rat model. Hypertonicity is traumatic to the cells of all organisms. Cells survive in a hypertonic environment by increasing the transcription of genes whose products catalyze cellular accumulation of compatible osmolytes. Inhibition of this crucial protein and its transduction process can result in deleterious effects on physiology. Hypertonicity in animals was achieved by treating animals with lithium orally, which lead to a condition known as diabetes insipidus with marked hypertonicity. Doxorubicin was used as a tool for the inhibition of TonEBP and related transduction pathway following which the various tests were performed to see the deleterious effects in vivo. On analysis, mean arterial pressure did not change except in the group where doxorubicin was used for inhibiting the TonEBP in lithium treated rats. Aldose reductase enzyme activity, which is one of the markers of hypertonicity was found to be increased in rats treated with lithium. Groups receiving combination therapy showed a decrease in enzyme activity. Serum amino acids analysis revealed an increase in levels of taurine, glycine and serine in lithium treated group and decrease in the groups with combination therapy. In combination group of lithium and doxorubicin, serum creatinine was significantly higher. There were changes as well in the levels of blood electrolytes like sodium, chloride and potassium. Histopathological studies on the kidney showed only mild degeneration in the group treated with lithium along with doxorubicin. Lithium administration develops a hypertonic state, which is evident with the increase in the rate-limiting biosynthetic enzymes— aldose reductase (AR) for sorbitol and also causes overexpression of some amino acids, which are osmoprotective in nature. When the expression of TonEBP was inhibited with doxorubicin in a dose dependent manner it resulted in alterations in the biochemical parameters.

Author(s): Aniket Kumar, Winston A B , Mahalakshmi C, Soosai Manickam Amirtham, Manoj G. Tyagi
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