Effects of antiemetic drugs on glucose 6-phosphate dehydrogenase and some antioxidant enzymes.
The aim of this study was to investigate effect of antiemetics on G6PD and antioxidant enzymes. Antiemetics are currently being used to reduce or prevent nausea and vomiting in patients. This is the first study to show effect of antiemetics on glucose-6-phosphate dehydrogenase (G6PD) and antioxidant enzyme activities. For in vitro studies, G6PD was purified from human erythrocyte, 10, 26-fold in a yield of 51.3% by using ammonium sulphate precipitation and 2',5'-ADP-Sepharose 4B affinity gel. The purified enzyme showed a single band on sodium dodecyl sulfate-polyacrilamide gel electrophoresis (SDS-PAGE). The effects of four different antiemetics (granisetron hydrochloride, ondansetron hydrochloride, metoclopramide hydrochloride, trimethobenzamide hydrochloride) were investigated on the purified enzyme. Granisetron hydrochloride and ondansetron hydrochloride inhibited the enzyme activity (Ki values; 5.05 mM and 0.034 mM, I50 values; 3.9 mM and 0.036 mM, respectively). Metoclopramide hydrochloride, trimethobenzamide hydrochloride showed no inhibition effects. In addition, in vivo studies, effects of ondansetron hydrochloride on the G6PD, glutathione reductase (GR), glutathione peroxidase (GPx) and catalase (CAT) were examined in the rat erythrocytes. G6PD (49% of control), GR (55% of control), CAT (60% of control) activities in erythrocytes were significantly decreased whereas GPx (183% of control) was significantly increased. A marked alteration in these enzymes may be result of oxidative stress in the rats receiving ondansetron hydrochloride.
Ozmen
Ismail
I
Biotechnology Application and Research Center, Atatürk University, 25240 Erzurum, Turkey. iozmen@atauni.edu.tr
Küfrevioglu
O Irfan
OI
D000818:Animals; D000932:Antiemetics / Q000494:pharmacology*; D000975:Antioxidants / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects / Q000201:enzymology; D005954:Glucosephosphate Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D008297:Male; D051381:Rats; D018709:Statistics, Nonparametric
D000932:Antiemetics; D000975:Antioxidants; D004791:Enzyme Inhibitors; D005954:Glucosephosphate Dehydrogenase