Effects of some anti-neoplastic drugs on sheep liver sorbitol dehydrogenase.
Stress is an important factor for many diseases in living metabolisms. The mini pathway named as polyol is a critical junction for stress factors. This pathway has two enzymes: aldose reductase (AR) and sorbitol dehydrogenase (SDH). It is linked with some diseases such as diabetes mellitus and some cancer types. In particular, SDH is very sensitive and unstable in in vitro conditions. In this study, SDH was purified by using simple and rapid chromatographic methods such as DEAE-Sephadex and CM-Sephadex C-50 columns. Subunit and active form molecular weights were found as 39.8 kDa and 150 kDa, respectively. The in vitro effects of some antineoplastic drugs were investigated. IC(50) values were 0.025, 0.081, 0.291, 1.62, 4.86, 6.54 mM for dacarbazine, methotrexate, epirubicin hydrochloride, calcium folinate, gemcitabine hydrochloride, oxaliplatin, respectively. From these results, dacarbazine was lowest IC(50) value and it is the strongest inhibitor for liver SDH enzyme activity compared to the other drugs.
Atatürk University, Faculty of Sciences, Department of Chemistry, Biochemistry Division, 25240, Turkey-Erzurum.
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D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D011232:Chemical Precipitation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004795:Enzyme Stability; D020128:Inhibitory Concentration 50; D007064:L-Iditol 2-Dehydrogenase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000302:isolation & purification; D008099:Liver / Q000201:enzymology; D008970:Molecular Weight; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D012756:Sheep
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D007064:L-Iditol 2-Dehydrogenase